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Sample records for cells persist years

  1. DNA-crosslinker cisplatin eradicates bacterial persister cells.

    Science.gov (United States)

    Chowdhury, Nityananda; Wood, Thammajun L; Martínez-Vázquez, Mariano; García-Contreras, Rodolfo; Wood, Thomas K

    2016-09-01

    For all bacteria, nearly every antimicrobial fails since a subpopulation of the bacteria enter a dormant state known as persistence, in which the antimicrobials are rendered ineffective due to the lack of metabolism. This tolerance to antibiotics makes microbial infections the leading cause of death worldwide and makes treating chronic infections, including those of wounds problematic. Here, we show that the FDA-approved anti-cancer drug cisplatin [cis-diamminodichloroplatinum(II)], which mainly forms intra-strand DNA crosslinks, eradicates Escherichia coli K-12 persister cells through a growth-independent mechanism. Additionally, cisplatin is more effective at killing Pseudomonas aeruginosa persister cells than mitomycin C, which forms inter-strand DNA crosslinks, and cisplatin eradicates the persister cells of several pathogens including enterohemorrhagic E. coli, Staphylococcus aureus, and P. aeruginosa. Cisplatin was also highly effective against clinical isolates of S. aureus and P. aeruginosa. Therefore, cisplatin has broad spectrum activity against persister cells. Biotechnol. Bioeng. 2016;113: 1984-1992. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

    International Nuclear Information System (INIS)

    Labadie, Karine; Pelletier, Isabelle; Saulnier, Aure; Martin, Javier; Colbere-Garapin, Florence

    2004-01-01

    Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

  3. Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy

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    Anna C. Hearps

    2017-06-01

    Full Text Available Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART. We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded in HIV+ individuals. Here, we analyzed a cohort of HIV+ men who have sex with men (MSM, n = 20 at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15 to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69+ and late (HLA-DR+/CD38+ activation were elevated in cART-naïve HIV+ MSM (p = 0.004 and 0.015, respectively, as were FcRγ− NK cells (p = 0.003. Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ− NK cells (p = 0.115 or activated HLA-DR+/CD38+ NK cells (p = 0.129 but did reduce T cell and monocyte activation (p < 0.001 for all. Proportions of FcRγ− NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56dim FcRγ− NK cell expansion and immune activation in HIV+ individuals. While proportions of activated CD69+ NK cells declined significantly on cART (p = 0.003, the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that 2 years of suppressive cART have no impact on CD56dim FcRγ− NK cell expansion and that NK cell activation persists after normalization of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV+ individuals on cART.

  4. Novel protocol for persister cells isolation.

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    Silvia J Cañas-Duarte

    Full Text Available Bacterial persistence, where a fraction of a population presents a transient resistance to bactericidal substances, has great medical importance due to its relation with the appearance of antibiotic resistances and untreatable bacterial chronic infections. The mechanisms behind this phenomenon remain largely unknown in spite of recent advances, in great part because of the difficulty in isolating the very small fraction of the population that is in this state at any given time. Current protocols for persister isolation have resulted in possible biases because of the induction of this state by the protocol itself. Here we present a novel protocol that allows rapid isolation of persister cells both from exponential and stationary phase. Moreover, it is capable of differentiating between type I and type II persister cells, which should allow the field to move beyond its current state of studying only one type. While this protocol prompts a revision of many of the current results, it should greatly facilitate further advances in the field.

  5. Effects of interferon on cultured cells persistently infected with viruses

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    Crespi, M

    1986-01-01

    The role of interferon (IFN) in viral persistence at the cellular level was investigated. Two types of persistent infections were chosen. The first type was cell lines which contained hepatitis B virus (HBV) DNA (PLC/PRF/5 and Hep 3B cells) uninfected control hepatoma cells, (Mahlavu, HA22T and Hep G2 cells) or simian virus 40 (SV40) DNA (C2, C6, C11 cells) and control uninfected (CV-1 cells). In the second type of infection Vero cells persistently infected with SSPE or Sendai virus were used. The aim of this work was to determine what effect IFN had in these infections in terms of its antiviral and antiproliferative effects; which of the two major IFN-induced pathways, E enzyme or protein kinase were induced; whether there were any differences in sensitivity to IFN between the DNA and RNA virus persistent infections. The anti-viral effect of IFN was examined by its ability to inhibit Sindbis virus replication using a radioimmunoassay system. The antiproliferative effect of IFN was determined by cell counting and /sup 3/H-thymidine incorporation. The activation of the ribonuclease F, determined by the inhibition of /sup 3/H-leucine incorporation after introduction of 2-5 actin into the cells, was variable, being activated in all cell lines with the exception of the PLC/PRF/5, Hep 3B and Hep G2 cells. Major differences between the two DNA persistent infections and the two RNA persistent infections were found. No correlation was found between the presence of HBV or SV40 persistent infections and the sensitivity of the cell lines to IFN. Both the SSPE and Sendai virus persistent infections were resistant to the antiviral and antiproliferative effect of IFN.

  6. Rapid Elimination of the Persistent Synergid through a Cell Fusion Mechanism

    KAUST Repository

    Maruyama, Daisuke

    2015-05-01

    In flowering plants, fertilization-dependent degeneration of the persistent synergid cell ensures one-on-one pairings of male and female gametes. Here, we report that the fusion of the persistent synergid cell and the endosperm selectively inactivates the persistent synergid cell in Arabidopsis thaliana. The synergid-endosperm fusion causes rapid dilution of pre-secreted pollen tube attractant in the persistent synergid cell and selective disorganization of the synergid nucleus during the endosperm proliferation, preventing attractions of excess number of pollen tubes (polytubey). The synergid-endosperm fusion is induced by fertilization of the central cell, while the egg cell fertilization predominantly activates ethylene signaling, an inducer of the synergid nuclear disorganization. Therefore, two female gametes (the egg and the central cell) control independent pathways yet coordinately accomplish the elimination of the persistent synergid cell by double fertilization. Two female gametes (the egg cell and the central cell) in flowering plants coordinately prevent attractions of excess number of pollen tubes via two mechanisms to inactivate persistent synergid cell. © 2015 Elsevier Inc.

  7. Persistence of Yellow Fever vaccine-induced antibodies after cord blood stem cell transplant.

    Science.gov (United States)

    Avelino-Silva, Vivian Iida; Freire, Marcos da Silva; Rocha, Vanderson; Rodrigues, Celso Arrais; Novis, Yana Sarkis; Sabino, Ester C; Kallas, Esper Georges

    2016-04-02

    We report the case of a cord blood haematopoietic stem cell transplant recipient who was vaccinated for Yellow Fever (YF) 7 days before initiating chemotherapy and had persistent YF antibodies more than 3 years after vaccination. Since the stem cell donor was never exposed to wild YF or to the YF vaccine, and our patient was not exposed to YF or revaccinated, this finding strongly suggests the persistence of recipient immunity. We briefly discuss potential consequences of incomplete elimination of recipient's leukocytes following existing haematopoietic cancer treatments.

  8. Extinct type of human parvovirus B19 persists in tonsillar B cells

    OpenAIRE

    Pyöriä, Lari; Toppinen, Mari; Mantyla, Elina; Hedman, Lea; Aaltonen, Leena-Maija; Vihinen-Ranta, Maija; Ilmarinen, Taru; Soderlund-Venermo, Maria; Hedman, Klaus; Perdomo, Maria

    2017-01-01

    Parvovirus B19 (B19V) DNA persists lifelong in human tissues, but the cell type harbouring it remains unclear. We here explore B19V DNA distribution in B, T and monocyte cell lineages of recently excised tonsillar tissues from 77 individuals with an age range of 2?69 years. We show that B19V DNA is most frequent and abundant among B cells, and within them we find a B19V genotype that vanished from circulation >40 years ago. Since re-infection or re-activation are unlikely with this virus type...

  9. Transmission of persistent ionizing radiation-induced foci through cell division in human primary cells

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    Vaurijoux, Aurelie, E-mail: aurelie.vaurijoux@irsn.fr [Institut de Radioprotection et de Sureté Nucléaire (IRSN), Laboratoire de Dosimétrie Biologique, BP 17, 92262 Fontenay aux roses cedex (France); Voisin, Pascale; Freneau, Amelie [Institut de Radioprotection et de Sureté Nucléaire (IRSN), Laboratoire de Dosimétrie Biologique, BP 17, 92262 Fontenay aux roses cedex (France); Barquinero, Joan Francesc [Universitat Autònoma de Barcelona, Faculty of Biosciences, 08193 Cerdanyola del Vallès (Spain); Gruel, Gaetan [Institut de Radioprotection et de Sureté Nucléaire (IRSN), Laboratoire de Dosimétrie Biologique, BP 17, 92262 Fontenay aux roses cedex (France)

    2017-03-15

    Highlights: • Persistent IRIF do not permanently block cell proliferation. • Persistent IRIF are transmitted in part and sometimes asymmetrically to daughter cells. • IRIF differ in their nature before and after the first cell division. - Abstract: Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24 h after irradiation. Their relation to unrepaired DSBs is generally accepted but still controversial. This study evaluates the frequency and kinetics of persistent IRIF and analyzes their impact on cell proliferation. We observed persistent IRIF up to 7 days postirradiation, and more than 70% of cells exposed to 5 Gy had at least one of these persistent IRIF 24 h after exposure. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, due to asymmetric distribution of IRIF between some of them. We report a positive association between the presence of IRIF and the likelihood of DNA missegregation. Hence, the structure formed after the passage of a persistent IRI focus across the S and G2 phases may impede the correct segregation of the affected chromosome's sister chromatids. The ensuing abnormal resolution of anaphase might therefore cause the nature of IRIF in daughter-cell nuclei to differ before and after the first cell division. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possibly enhanced genomic instability, in particular in the daughter cells.

  10. Transmission of persistent ionizing radiation-induced foci through cell division in human primary cells

    International Nuclear Information System (INIS)

    Vaurijoux, Aurelie; Voisin, Pascale; Freneau, Amelie; Barquinero, Joan Francesc; Gruel, Gaetan

    2017-01-01

    Highlights: • Persistent IRIF do not permanently block cell proliferation. • Persistent IRIF are transmitted in part and sometimes asymmetrically to daughter cells. • IRIF differ in their nature before and after the first cell division. - Abstract: Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24 h after irradiation. Their relation to unrepaired DSBs is generally accepted but still controversial. This study evaluates the frequency and kinetics of persistent IRIF and analyzes their impact on cell proliferation. We observed persistent IRIF up to 7 days postirradiation, and more than 70% of cells exposed to 5 Gy had at least one of these persistent IRIF 24 h after exposure. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, due to asymmetric distribution of IRIF between some of them. We report a positive association between the presence of IRIF and the likelihood of DNA missegregation. Hence, the structure formed after the passage of a persistent IRI focus across the S and G2 phases may impede the correct segregation of the affected chromosome's sister chromatids. The ensuing abnormal resolution of anaphase might therefore cause the nature of IRIF in daughter-cell nuclei to differ before and after the first cell division. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possibly enhanced genomic instability, in particular in the daughter cells.

  11. Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

    Science.gov (United States)

    Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan

    2017-10-01

    Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.

  12. Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene expression

    International Nuclear Information System (INIS)

    Hoever, Gerold; Vogel, Jens-Uwe; Lukashenko, Polina; Hofmann, Wolf-Karsten; Komor, Martina; Doerr, Hans Wilhelm; Cinatl, Jindrich

    2005-01-01

    In a model of human neuroblastoma (NB) cell lines persistently infected with human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection is associated with an increased malignant phenotype, enhanced drug resistance, and invasive properties. To gain insights into the mechanisms of increased malignancy we analyzed the global changes in cellular gene expression induced by persistent HCMV infection of human neuroblastoma cells by use of high-density oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene expression of different NB cell lines with persistently infected cell sub-lines revealed 11 host cell genes regulated in a similar manner throughout all infected samples. Nine of these 11 genes may contribute to the previously observed changes in malignant phenotype of persistently HCMV infected NB cells by influencing invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work provides the basis for further functional studies

  13. Saffold Virus Type 3 (SAFV-3) Persists in HeLa Cells

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    Himeda, Toshiki; Hosomi, Takushi; Okuwa, Takako; Muraki, Yasushi; Ohara, Yoshiro

    2013-01-01

    Saffold virus (SAFV) was identified as a human cardiovirus in 2007. Although several epidemiological studies have been reported, they have failed to provide a clear picture of the relationship between SAFV and human diseases. SAFV genotype 3 has been isolated from the cerebrospinal fluid specimen of patient with aseptic meningitis. This finding is of interest since Theiler’s murine encephalomyelitis virus (TMEV), which is the closely related virus, is known to cause a multiple sclerosis-like syndrome in mice. TMEV persistently infects in mouse macrophage cells in vivo and in vitro, and the viral persistence is essential in TMEV-induced demyelinating disease. The precise mechanism(s) of SAFV infection still remain unclear. In order to clarify the SAFV pathogenicity, in the present study, we studied the possibilities of the in vitro persistent infection of SAFV. The two distinct phenotypes of HeLa cells, HeLa-N and HeLa-R, were identified. In these cells, the type of SAFV-3 infection was clearly different. HeLa-N cells were lyticly infected with SAFV-3 and the host suitable for the efficient growth. On the other hand, HeLa-R cells were persistently infected with SAFV-3. In addition, the SAFV persistence in HeLa-R cells is independent of type I IFN response of host cells although the TMEV persistence in mouse macrophage cells depends on the response. Furthermore, it was suggested that SAFV persistence may be influenced by the expression of receptor(s) for SAFV infection on the host cells. The present findings on SAFV persistence will provide the important information to encourage the research of SAFV pathogenicity. PMID:23308162

  14. Persistent Fatigue in Hematopoietic Stem Cell Transplantation Survivors.

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    Hacker, Eileen Danaher; Fink, Anne M; Peters, Tara; Park, Chang; Fantuzzi, Giamila; Rondelli, Damiano

    Fatigue is highly prevalent after hematopoietic stem cell transplantation (HCT). It has been described as intense and may last for years following treatment. The aim of this study is to compare fatigue, physical activity, sleep, emotional distress, cognitive function, and biological measures in HCT survivors with persistent fatigue (n = 25) with age- and gender-matched healthy controls with occasional tiredness (n = 25). Data were collected using (a) objective, real-time assessments of physical activity and sleep over 7 days; (b) patient-reported fatigue assessments; (c) computerized objective testing of cognitive functioning; and (d) biological measures. Differences between groups were examined using multivariate analysis of variance. Survivors of HCT reported increased physical (P < .001), mental (P < .001), and overall (P < .001) fatigue as well as increased anxiety (P < .05) and depression (P < .01) compared with healthy controls. Red blood cell (RBC) levels were significantly lower in HCT survivors (P < .001). Levels of RBC for both groups, however, were in the normal range. Tumor necrosis factor-α (P < .001) and interleukin-6 (P < .05) levels were significantly higher in HCT survivors. Persistent fatigue in HCT survivors compared with healthy controls with occasional tiredness is accompanied by increased anxiety and depression along with decreased RBC counts. Elevated tumor necrosis factor-α and interleukin-6 levels may be important biomarkers. This study provides preliminary support for the conceptualization of fatigue as existing on a continuum, with tiredness anchoring one end and exhaustion the other. Persistent fatigue experienced by HCT survivors is more severe than the occasional tiredness of everyday life.

  15. New-found fundamentals of bacterial persistence.

    Science.gov (United States)

    Kint, Cyrielle I; Verstraeten, Natalie; Fauvart, Maarten; Michiels, Jan

    2012-12-01

    Persister cells display tolerance to high doses of bactericidal antibiotics and typically comprise a small fraction of a bacterial population. Recently, evidence was provided for a causal link between therapy failure and the presence of persister cells in chronic infections, underscoring the need for research on bacterial persistence. A series of recent breakthroughs have shed light on the multiplicity of persister genes, the contribution of gene expression noise to persister formation, the importance of active responses to antibiotic tolerance and heterogeneity among persister cells. Moreover, the development of in vivo model systems has highlighted the clinical relevance of persistence. This review discusses these recent advances and how this knowledge fundamentally changes the way in which we will perceive the problem of antibiotic tolerance in years to come. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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    Dajana Reuter

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

  17. Is bacterial persistence a social trait?

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    Andy Gardner

    Full Text Available The ability of bacteria to evolve resistance to antibiotics has been much reported in recent years. It is less well-known that within populations of bacteria there are cells which are resistant due to a non-inherited phenotypic switch to a slow-growing state. Although such 'persister' cells are receiving increasing attention, the evolutionary forces involved have been relatively ignored. Persistence has a direct benefit to cells because it allows survival during catastrophes-a form of bet-hedging. However, persistence can also provide an indirect benefit to other individuals, because the reduced growth rate can reduce competition for limiting resources. This raises the possibility that persistence is a social trait, which can be influenced by kin selection. We develop a theoretical model to investigate the social consequences of persistence. We predict that selection for persistence is increased when: (a cells are related (e.g. a single, clonal lineage; and (b resources are scarce. Our model allows us to predict how the level of persistence should vary with time, across populations, in response to intervention strategies and the level of competition. More generally, our results clarify the links between persistence and other bet-hedging or social behaviours.

  18. Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes.

    Science.gov (United States)

    Alidjinou, E K; Engelmann, I; Bossu, J; Villenet, C; Figeac, M; Romond, M-B; Sané, F; Hober, D

    2017-10-03

    Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated. A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated. The profile of cellular microRNAs (miRNAs) was investigated through miRNA-sequencing. Viral phenotypic changes were examined, and genomic modifications were assessed by sequencing of the viral genome. The CVB4 persistence in ductal-like cells was productive, with continuous release of infectious particles. Persistently infected cells displayed a resistance to CVB4-induced lysis upon superinfection and expression of PDX-1 and CAR was decreased. These changes were maintained even after virus clearance. The patterns of cellular miRNA expression in mock-infected and in CVB4-persistently infected ductal-like cells were clearly different. The persistent infection-derived virus (PIDV) was still able to induce cytopathic effect but its plaques were smaller than the parental virus. Several mutations appeared in various PIDV genome regions, but amino acid substitutions did not affect the predicted site of interaction with CAR. Cellular and viral changes occur during persistent infection of human pancreas ductal-like cells with CVB4. The persistence of cellular changes even after virus clearance supports the hypothesis of a long-lasting impact of persistent CVB infection on the cells.

  19. Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.

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    Anjie Zhen

    2017-12-01

    Full Text Available Chimeric Antigen Receptor (CAR T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV infection in pigtail macaques. CAR-containing cells persisted for more than 2 years without any measurable toxicity and were capable of multilineage engraftment. Combination antiretroviral therapy (cART treatment followed by cART withdrawal resulted in lower viral rebound in CAR animals relative to controls, and demonstrated an immune memory-like response. We found CAR-expressing cells in multiple lymphoid tissues, decreased tissue-associated SHIV RNA levels, and substantially higher CD4/CD8 ratios in the gut as compared to controls. These results show that HSPC-derived CAR T-cells are capable of long-term engraftment and immune surveillance. This study demonstrates for the first time the safety and feasibility of HSPC-based CAR therapy in a large animal preclinical model.

  20. Epidemiology of frequent attenders: a 3-year historic cohort study comparing attendance, morbidity and prescriptions of one-year and persistent frequent attenders

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    ter Riet Gerben

    2009-01-01

    Full Text Available Abstract Background General Practitioners spend a disproportionate amount of time on frequent attenders. So far, trials on the effect of interventions on frequent attenders have shown negative results. However, these trials were conducted in short-term frequent attenders. It would be more reasonable to target intervention at persistent frequent attenders. Typical characteristics of persistent frequent attenders, as opposed to 1-year frequent attenders and non-frequent attenders, may generate hypotheses regarding modifiable factors on which new randomized trials may be designed. Methods We used the data of all 28,860 adult patients from 5 primary healthcare centers. Frequent attenders were patients whose attendance rate ranked in the (age and sex adjusted top 10 percent during 1 year (1-year frequent attenders or 3 years (persistent frequent attenders. All other patients on the register over the 3-year period were referred to as non-frequent attenders. The lists of medical problems coded by the GP using the International Classification of Primary Care (ICPC were used to assess morbidity. First, we determined which proportion of 1-year frequent attenders was still a frequent attender during the next two consecutive years and calculated the GPs' workload for these patients. Second, we compared morbidity and number of prescriptions for non-frequent attenders, 1-year frequent attenders and persistent frequent attenders. Results Of all 1-year frequent attenders, 15.4% became a persistent frequent attender equal to 1.6% of all patients. The 1-year frequent attenders (3,045; 10.6% were responsible for 39% of the face-to-face consultations; the 470 patients who would become persistent frequent attenders (1.6% were responsible for 8% of all consultations in 2003. Persistent frequent attenders presented more social problems, more psychiatric problems and medically unexplained physical symptoms, but also more chronic somatic diseases (especially diabetes

  1. One-year post-primary antibody persistence and booster immune ...

    African Journals Online (AJOL)

    One-year post-primary antibody persistence and booster immune response to a DTaP-IPV//PRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6, 10 and 14 weeks of age with the same vaccine.

  2. Autocatalytic polymerization generates persistent random walk of crawling cells.

    Science.gov (United States)

    Sambeth, R; Baumgaertner, A

    2001-05-28

    The autocatalytic polymerization kinetics of the cytoskeletal actin network provides the basic mechanism for a persistent random walk of a crawling cell. It is shown that network remodeling by branching processes near the cell membrane is essential for the bimodal spatial stability of the network which induces a spontaneous breaking of isotropic cell motion. Details of the phenomena are analyzed using a simple polymerization model studied by analytical and simulation methods.

  3. Persistent disorders of mineral metabolism after one year of kidney transplantation.

    Science.gov (United States)

    Gomes, Larissa Kruger; Custódio, Melani Ribeiro; Contieri, Fabiana Loss de Carvalho; Riella, Miguel C; Nascimento, Marcelo Mazza do

    2016-01-01

    The persistence of mineral metabolism disorders after renal transplant (RT) appears to possess a negative impact over graft and patient's survival. To evaluate the parameters of mineral metabolism and the persistence of hyperparathyroidism (HPT) in transplanted patients for a 12-month period after the procedure. Retrospective analysis of 41 transplants (18 women- 44%, mean age of 39 ± 15 years) performed in a University Hospital, evaluating changes of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) and the prevalence of persistent HPT. The patients were divided into two groups accordingly to PTH levels prior to Tx: Group 1 with PTH ≤ 300 pg/mL (n = 21) and Group 2 with PTH > 300 pg/mL (n = 20). The persistency of HPT after transplant was defined as PTH ≥ 100 pg/mL. The evolution of biochemical parameters and the persistency of HPT were analyzed in each group after 1 year of transplant. After a one-year of follow up, 5% of the patients presented hypophosphatemia (p 10.2 mg/dL) and 48% persistency of HPT (PTH ≥ 100 pg/mL). There was a positive correlation between the PTH pre and post Tx (r = 0.42/p = 0.006) and a negative correlation between PTH and Ca pre-Tx (r = -0.45/p = 0.002). However, there was no significant difference among groups 1 and 2 regarding PTH levels pre and post Tx. The findings in this article suggest that mineral metabolism alterations and the persistency of HPT may occur after one year of renal Tx, mainly in patients which present high PTH levels prior toTx. A persistência de distúrbios do metabolismo mineral ósseo após o transplante renal (Tx) parece possuir um impacto negativo sobre a sobrevida do enxerto e do paciente. avaliar os parâmetros do metabolismo mineral e a persistência de hiperparatiroidismo (pHPT) 12 meses após o Tx. Análise retrospectiva de 41 transplantes (18 mulheres- 44%, idade de 39 ± 15 anos) realizados em um Hospital Universitário, avaliando cálcio (Ca), fósforo (P), hormônio da paratire

  4. Polypeptide synthesis in alphavirus-infected aedes albopictus cells during the establishment of persistent infection

    International Nuclear Information System (INIS)

    Richardson, M.A.; Boulton, R.W.; Raghow, R.S.; Dalgarno, L.

    1980-01-01

    Polypeptide synthesis was examined in mosquito cells during the establishment of a persistent infection with two alphaviruses, Ross River virus (RRV) and Semliki Forest virus (SFV), and in vertebrate cells cytopathically-infected with the same viruses. In Aedes albopictus cells, RRV reached peak titres at 34-48 hours p.i. At 12 hours 85 per cent of cells assayed as infected by infective centre assay; by 48 hours when persistence was established, virus production was reduced and <5 per cent of cells assayed as infected. There was not shutdown of host polypeptide synthesis during infection. Viral polypeptide synthesis was maximal between 10 and 24 hours p.i. The major viral polypeptides labelled were nucleocapsid protein and envelope protein(s).The precursor polypeptide p95 which was prominent in infected BHK cells was not detected in mosquito cells. Similar results were obtained on SFV infection. During the establishment of persistence there was a coordinate decline in the synthesis of RRV polypeptides, reaching undetectable levels by 72 hours p.i. Subculturing persistently-infected cells led to a small increase in viral polypeptide synthesis and virus titre. In contrast, during RRV growth in BHK cells host protein synthesis was severely inhibited and by 9-11 hours p.i. virus-specific polypeptide synthesis represented more than 90 per cent of total protein synthetic activity. (author)

  5. Impaired antibody response causes persistence of prototypic T cell-contained virus.

    Directory of Open Access Journals (Sweden)

    Andreas Bergthaler

    2009-04-01

    Full Text Available CD8 T cells are recognized key players in control of persistent virus infections, but increasing evidence suggests that assistance from other immune mediators is also needed. Here, we investigated whether specific antibody responses contribute to control of lymphocytic choriomeningitis virus (LCMV, a prototypic mouse model of systemic persistent infection. Mice expressing transgenic B cell receptors of LCMV-unrelated specificity, and mice unable to produce soluble immunoglobulin M (IgM exhibited protracted viremia or failed to resolve LCMV. Virus control depended on immunoglobulin class switch, but neither on complement cascades nor on Fc receptor gamma chain or Fc gamma receptor IIB. Cessation of viremia concurred with the emergence of viral envelope-specific antibodies, rather than with neutralizing serum activity, and even early nonneutralizing IgM impeded viral persistence. This important role for virus-specific antibodies may be similarly underappreciated in other primarily T cell-controlled infections such as HIV and hepatitis C virus, and we suggest this contribution of antibodies be given consideration in future strategies for vaccination and immunotherapy.

  6. Urinary incontinence persisting after childbirth: extent, delivery history, and effects in a 12-year longitudinal cohort study.

    Science.gov (United States)

    MacArthur, C; Wilson, D; Herbison, P; Lancashire, R J; Hagen, S; Toozs-Hobson, P; Dean, N; Glazener, C

    2016-05-01

    To investigate the extent of persistent urinary incontinence (UI) 12 years after birth, and association with delivery-mode history and other factors. Twelve-year longitudinal cohort study. Maternity units in Aberdeen, Birmingham, and Dunedin. Women who returned questionnaires 3 months and 12 years after index birth. Data on all births over a period of 12 months were obtained from the units and then women were contacted by post. Persistent UI reported at 12 years, with one or more previous contact. Of 7879 women recruited at 3 months, 3763 (48%) responded at 12 years, with 2944 also having responded at 6 years; non-responders had similar obstetric characteristics. The prevalence of persistent UI was 37.9% (1429/3763). Among those who had reported UI at 3 months, 76.4% reported it at 12 years. Women with persistent UI had lower SF12 quality of life scores. Compared with having only spontaneous vaginal deliveries (SVDs), women who delivered exclusively by caesarean section were less likely to have persistent UI (odds ratio, OR 0.42, 95% CI 0.33-0.54). This was not the case in women who had a combination of caesarean section and SVD births (OR 1.01, 95% CI 0.78-1.30). Older age at first birth, greater parity, and overweight/obesity were associated with persistent UI. Of 54 index primiparae with UI before pregnancy, 46 (85.2%) had persistent UI. This study, demonstrating that UI persists to 12 years in about three-quarters of women, and that risk was only reduced with caesarean section if women had no other delivery mode, has practice implications. A longitudinal study of 3763 women showed a prevalence of persistent UI 12 years after birth of 37.9%. © 2015 Royal College of Obstetricians and Gynaecologists.

  7. Design approach for solar cell and battery of a persistent solar powered GPS tracker

    Science.gov (United States)

    Sahraei, Nasim; Watson, Sterling M.; Pennes, Anthony; Marius Peters, Ian; Buonassisi, Tonio

    2017-08-01

    Sensors with wireless communication can be powered by photovoltaic (PV) devices. However, using solar power requires thoughtful design of the power system, as well as a careful management of the power consumption, especially for devices with cellular communication (because of their higher power consumption). A design approach can minimize system size, weight, and/or cost, while maximizing device performance (data transmission rate and persistence). In this contribution, we describe our design approach for a small form-factor, solar-powered GPS tracker with cellular communication. We evaluate the power consumption of the device in different stages of operation. Combining measured power consumption and the calculated energy-yield of a solar cell, we estimate the battery capacity and solar cell area required for 5 years of continuous operation. We evaluate trade-offs between PV and battery size by simulating the battery state of charge. The data show a trade-off between battery capacity and solar-cell area for given target data transmission rate and persistence. We use this analysis to determine the combination of solar panel area and battery capacity for a given application and the data transmission rate that results in minimum cost or total weight of the system.

  8. Recombinant cells and organisms having persistent nonstandard amino acid dependence and methods of making them

    Science.gov (United States)

    Church, George M.; Mandell, Daniel J.; Lajoie, Marc J.

    2017-12-05

    Recombinant cells and recombinant organisms persistently expressing nonstandard amino acids (NSAAs) are provided. Methods of making recombinant cells and recombinant organisms dependent on persistently expressing NSAAs for survival are also provided. These methods may be used to make safe recombinant cells and recombinant organisms and/or to provide a selective pressure to maintain one or more reassigned codon functions in recombinant cells and recombinant organisms.

  9. Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.

    Science.gov (United States)

    Mizoguchi, Takamasa; Ikeda, Shoko; Watanabe, Saori; Sugawara, Michiko; Itoh, Motoyuki

    2017-10-31

    Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood. Here, we show that the ubiquitin ligase mind bomb 1 (Mib1) is involved in persistent directional cell migration. We found that knockdown of MIB1 led to an increase in random cell migration in HeLa cells in a wound-closure assay. Furthermore, we explored novel Mib1 substrates for cell migration and found that Mib1 ubiquitinates Ctnnd1. Mib1-mediated ubiquitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1 ta52b mutant showed increased random migration and loss of directional F-actin-based protrusion formation. Knockdown of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1 ta52b mutant. Taken together, our data suggest that Mib1 plays an important role in cell migration and that persistent directional cell migration is regulated, at least in part, by the Mib1-Ctnnd1-Rac1 pathway. Published under the PNAS license.

  10. Quorum Sensing-Regulated Phenol-Soluble Modulins Limit Persister Cell Populations in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Bojer, Martin S; Lindemose, Søren; Vestergaard, Martin

    2018-01-01

    Incomplete killing of bacterial pathogens by antibiotics is an underlying cause of treatment failure and accompanying complications. Among those avoiding chemotherapy are persisters being individual cells in a population that for extended periods of time survive high antibiotic concentrations...... proposedly by being in a quiescent state refractory to antibiotic killing. While investigating the human pathogenStaphylococcus aureusand the influence of growth phase on persister formation, we noted that spent supernatants of stationary phase cultures ofS. aureusorS. epidermidis, but not of distantly...... related bacteria, significantly reduced the persister cell frequency upon ciprofloxacin challenge when added to exponentially growing and stationary phaseS. aureuscells. Curiously, the persister reducing activity ofS. aureussupernatants was also effective against persisters formed by eitherS. carnosusor...

  11. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    Full Text Available The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs, have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

  12. Persistence of cow's milk allergy beyond two years of age.

    Science.gov (United States)

    Dias, A; Santos, A; Pinheiro, J A

    2010-01-01

    Cow's milk allergy (CMA) epidemiology seems to be changing over time, with an increase in prevalence and persistence. Our aim was to characterise a population of children with CMA beyond two years of age, followed up in a Paediatric Allergy Clinic at the tertiary care level. Retrospective study of children with persistent CMA diagnosed from January 1997 to June 2006. Medical records were analysed regarding: clinical presentation, follow-up, treatment and acquisition of tolerance. Data analysis was performed using Excel 2007 for Windows. Seventy-nine children were included, with mean age at first symptoms of 3 months. The symptoms were immediate in 93%, with cutaneous (87.3%), gastrointestinal (55.7%) and respiratory (25.3%) manifestations. During the follow-up period, 30% developed atopic eczema, 52% asthma and 35% rhinoconjunctivitis. A family history of atopy was identified in 53%. The majority presented increased serum total IgE (376+/-723 KU/l) and positive skin prick test (SPT) to cow's milk (CM) (79%). SPT to goat's milk was positive in 2/3 of cases. Fifty-five percent had at least one accidental exposure to CM (severe reactions in 6%). During CM elimination diet, 35% were initially given an extensively hydrolysed formula, 17% a soy formula, and 48% both. By the age of 10 years, 44% of children persisted with CMA. Our population of CM allergic children presented immediate symptoms with cutaneous expression in the majority. Severe reactions were common on accidental exposure. By the age of 10 years, 44% maintained CMA, highlighting the importance of a multidisciplinary follow-up. Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

  13. Immunological aspects of persistent hepatitis B in children

    Directory of Open Access Journals (Sweden)

    Harsoyo Notoatmojo

    2006-08-01

    Full Text Available We studied the immunological status of 203 children having persistence Hepatitis B (positive HBsAg ranging in age from 6 to 14 years in Semarang Municipality. The results of humoral immunity examination (IgM Anti-HBc showed that all were negative, indicating that they are not in acute phase of hepatitis B infection. Cellular immunity examination, i.e., CMI skin test has shown positive result in 64.9% on persistent and 65.2% in non persistent hepatitis B (p>0.05. T cell examination showed statistically significant difference (p<0.01 between persistenct and non persistent hepatitis B patients, there was is also significant difference (p<0.01 on CD4 cell examination. These findings indicated that there was difference in immunoregulation function and response repression of antivirus between both groups of patients. On the other hand CD4/ CD8 ratio and T cell function showed no significant difference between the two gorups of patients; similarly the specific function of cytotoxic T cell was not significantly difference.

  14. Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children.

    Science.gov (United States)

    Weinberg, Adriana; Huang, Sharon; Moscicki, Anna-Barbara; Saah, Afred; Levin, Myron J

    2018-04-24

    To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group. B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.

  15. Prophages and growth dynamics confound experimental results with antibiotic-tolerant persister cells

    DEFF Research Database (Denmark)

    Harms, Alexander; Fino, Cinzia; Sørensen, Michael Askvad

    2017-01-01

    the validity of our model of persister formation in a refined assay setup that uses robust culture conditions and unravels the dynamics of persister cells through all bacterial growth stages. Our results confirm the importance of (p)ppGpp and Lon but no longer support a role of TA modules in E. coli persister......) modules. This model found considerable support among researchers studying persisters but also generated controversy as part of recent debates in the field. In this study, we therefore used our previous work as a model to critically examine common experimental procedures to understand and overcome......-tolerant persisters via induction of cryptic prophages. Similarly, the inadvertent infection of mutant strains with bacteriophage φ80, a notorious laboratory contaminant, apparently caused several of the phenotypes that we reported in our previous studies. We therefore reconstructed all infected mutants and probed...

  16. Late-onset persistent retinal microvascular changes after bone marrow transplantation: 3-year follow-up

    Directory of Open Access Journals (Sweden)

    Muccioli Cristina

    2002-01-01

    Full Text Available Purpose: To describe a case of persistent retinopathy after bone marrow transplantation in the absence of radiation therapy. Methods: Case Report. Results: A 42 year-old man developed bilateral visual loss 15 months after receiving a bone marrow transplant for acute leukemia. The patient was treated with a high dose of cyclosporin A and oral corticosteroids. No radiation therapy was given. Late-onset, multiple, bilateral cotton-wool spots developed 15 months after the bone marrow transplantation and still persist. After three years other cotton-wool spots arose in the absence of any immunosuppressive therapy. Conclusions: Bone marrow transplantation microvasculopathy of the retina may be related to certain combinations of chemotherapy drugs or immunosuppression itself and may persist in the absence of these immunosuppressive drugs.

  17. Redirection to the bone marrow improves T cell persistence and antitumor functions.

    Science.gov (United States)

    Khan, Anjum B; Carpenter, Ben; Santos E Sousa, Pedro; Pospori, Constandina; Khorshed, Reema; Griffin, James; Velica, Pedro; Zech, Mathias; Ghorashian, Sara; Forrest, Calum; Thomas, Sharyn; Gonzalez Anton, Sara; Ahmadi, Maryam; Holler, Angelika; Flutter, Barry; Ramirez-Ortiz, Zaida; Means, Terry K; Bennett, Clare L; Stauss, Hans; Morris, Emma; Lo Celso, Cristina; Chakraverty, Ronjon

    2018-05-01

    A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration toward vascular-associated CXCL12+ cells in the BM and increased their local engraftment. Increased access of TCXCR4 to the BM microenvironment induced IL-15-dependent homeostatic expansion and promoted the differentiation of memory precursor-like cells with low expression of programmed death-1, resistance to apoptosis, and a heightened capacity to generate polyfunctional cytokine-producing effector cells. Following transfer to lymphoma-bearing mice, TCXCR4 showed a greater capacity for effector expansion and better tumor protection, the latter being independent of changes in trafficking to the tumor bed or local out-competition of regulatory T cells. Thus, redirected homing of T cells to the BM confers increased memory differentiation and antitumor immunity, suggesting an innovative solution to increase the persistence and functions of therapeutic T cells.

  18. 20 Years of persistent identifiers - Which systems are here to stay?

    Science.gov (United States)

    Klump, Jens; Huber, Robert; Lehnert, Kerstin

    2016-04-01

    Web-based persistent identifiers have been around for more than 20 years, a period long enough to start observing patterns of success and failure. Persistent identifiers were invented to address challenges arising from the distributed and disorganised nature of the internet, which not only allowed new technologies to emerge, it also made it difficult to maintain a persistent record of science. Persistent identifiers now allow unambiguous identification of resources on the net. The expectations were that persistent identifiers would lead to greater accessibility, transparency and reproducibility of research results. Over the past two decades a number of persistent identifier systems have been built, one of them being Digital Object Identifiers (DOI). While DOI were originally invented by the publishing industry, they quickly became an established way for the identification of research resources. At first, these resources referred to scholarly literature and related resources. Other identifier systems, some of them using DOI as an example, were developed as grass-roots efforts by the scientific community. The concept of using persistent identifiers has since been expanded to other, non-textual resources, like datasets (DOI, EPIC) and geological specimens (IGSN), and more recently to authors and contributors of scholarly works (ORCID), and to software and instruments. A common witticism states that "a great thing about standards is that there are so many to choose from." Setting up identifier systems is technically trivial. The real challenge lies in creating a governance system for the respective identifiers. Which systems will stand the test of time? Drawing on data from the Registry of Research Data Repositories (re3data.org) and our own experience in the field, this presentation looks at the history and adoption of existing identifier systems and how this gives us some indications towards factors influencing sustainability of these systems.

  19. A pharmacological study of Arabidopsis cell fusion between the persistent synergid and endosperm.

    Science.gov (United States)

    Motomura, Kazuki; Kawashima, Tomokazu; Berger, Frédéric; Kinoshita, Tetsu; Higashiyama, Tetsuya; Maruyama, Daisuke

    2018-01-29

    Cell fusion is a pivotal process in fertilization and multinucleate cell formation. A plant cell is ubiquitously surrounded by a hard cell wall, and very few cell fusions have been observed except for gamete fusions. We recently reported that the fertilized central cell (the endosperm) absorbs the persistent synergid, a highly differentiated cell necessary for pollen tube attraction. The synergid-endosperm fusion (SE fusion) appears to eliminate the persistent synergid from fertilized ovule in Arabidopsis thaliana Here, we analyzed the effects of various inhibitors on SE fusion in an in vitro culture system. Different from other cell fusions, neither disruption of actin polymerization nor protein secretion impaired SE fusion. However, transcriptional and translational inhibitors decreased the SE fusion success rate and also inhibited endosperm division. Failures of SE fusion and endosperm nuclear proliferation were also induced by roscovitine, an inhibitor of cyclin-dependent kinases (CDK). These data indicate unique aspects of SE fusion such as independence of filamentous actin support and the importance of CDK-mediated mitotic control. © 2018. Published by The Company of Biologists Ltd.

  20. Predictors of the 2-year recurrence and persistence of alcohol dependence

    NARCIS (Netherlands)

    Boschloo, Lynn; Vogelzangs, Nicole; van den Brink, Wim; Smit, Johannes H.; Beekman, Aartjan T. F.; Penninx, Brenda

    Aims To identify independent risk factors of the recurrence of alcohol dependence (AD) in people with a remitted disorder at baseline and persistence of AD in people with a current disorder at baseline. Design Prospective cohort study with assessments at baseline and 2-year follow-up. Setting

  1. Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren's syndrome.

    Science.gov (United States)

    Hershberg, Uri; Meng, Wenzhao; Zhang, Bochao; Haff, Nancy; St Clair, E William; Cohen, Philip L; McNair, Patrice D; Li, Ling; Levesque, Marc C; Luning Prak, Eline T

    2014-02-11

    Subjects with primary Sjögren's syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab. To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection. For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an expanded clone may provide a novel means

  2. Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Megan C. Mladinich

    2017-07-01

    Full Text Available Zika virus (ZIKV is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons. We found that ZIKV (strain PRVABC59 persistently infects and continuously replicates in primary human brain microvascular ECs (hBMECs, without cytopathology, for >9 days and following hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB. ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-α and transiently induced, but failed to secrete, IFN-β and IFN-λ. Global transcriptome analysis determined that ZIKV constitutively induced IFN regulatory factor 7 (IRF7, IRF9, and IFN-stimulated genes (ISGs 1 to 9 days postinfection, despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15, HERC5, and USP18, which are linked to hepatitis C virus (HCV persistence and IFN regulation, chemokine CCL5, which is associated with immunopathogenesis, as well as cell survival factors. Our results reveal that hBMECs act as a reservoir of persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into neuronal compartments, and define novel mechanisms of ZIKV persistence that can be targeted to restrict ZIKV spread.

  3. Persistent Inflammation Alters the Function of the Endogenous Brain Stem Cell Compartment

    OpenAIRE

    Pluchino, Stefano; Muzio, Luca; Alfaro-Cervello, Clara; Salani, Giuliana; Porcheri, Cristina; Brambilla, Elena; Cavasinni, Francesca; Bergamaschi, Andrea; Garcia-Verdugo, Jose Manuel; Comi, Giancarlo; Martino, Gianvito; Imitola, Jaime; Deleidi, Michela; Khoury, Samia Joseph

    2008-01-01

    Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain in...

  4. Adherence and Persistence Among Statin Users Aged 65 Years and Over: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Ofori-Asenso, Richard; Jakhu, Avtar; Zomer, Ella; Curtis, Andrea J; Korhonen, Maarit Jaana; Nelson, Mark; Gambhir, Manoj; Tonkin, Andrew; Liew, Danny; Zoungas, Sophia

    2018-05-09

    Older people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence patterns among older statin users have not been comprehensively reviewed. As part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects, CENTRAL, and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/or persistence among older statin users. Data were analyzed via descriptive methods and meta-analysis using random-effect modeling. Data from more than 3 million older statin users in 82 studies conducted in over 40 countries were analyzed. At 1-year follow-up, 59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged more than 75 years than those aged 65-75 years. At 3 and ≥10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were nonadherent and 23.9% discontinued within the first year. The proportion of statin users who were adherent based on self-report was 85.5%. There is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realized.

  5. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

    Science.gov (United States)

    Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

    2015-02-01

    Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

  6. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Tanner M Johanns

    2010-08-01

    Full Text Available The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3-4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3(GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3(+ Treg suppressive potency. In complementary experiments using Foxp3(DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

  7. Evolution of a Cell Culture-Derived Genotype 1a Hepatitis C Virus (H77S.2) during Persistent Infection with Chronic Hepatitis in a Chimpanzee

    Science.gov (United States)

    Yi, MinKyung; Hu, Fengyu; Joyce, Michael; Saxena, Vikas; Welsch, Christoph; Chavez, Deborah; Guerra, Bernadette; Yamane, Daisuke; Veselenak, Ronald; Pyles, Rick; Walker, Christopher M.; Tyrrell, Lorne; Bourne, Nigel; Lanford, Robert E.

    2014-01-01

    challenged with cell culture-produced virus and provides novel insight into the forces shaping molecular evolution of that virus during 5 years of persistent infection. It demonstrates that a poorly fit virus can replicate for weeks within the liver in the absence of detectable viremia, an observation that expands current concepts of HCV pathogenesis and that is relevant to relapses observed with direct-acting antiviral therapies. PMID:24429362

  8. Evolution of a cell culture-derived genotype 1a hepatitis C virus (H77S.2) during persistent infection with chronic hepatitis in a chimpanzee.

    Science.gov (United States)

    Yi, MinKyung; Hu, Fengyu; Joyce, Michael; Saxena, Vikas; Welsch, Christoph; Chavez, Deborah; Guerra, Bernadette; Yamane, Daisuke; Veselenak, Ronald; Pyles, Rick; Walker, Christopher M; Tyrrell, Lorne; Bourne, Nigel; Lanford, Robert E; Lemon, Stanley M

    2014-04-01

    Persistent infection is a key feature of hepatitis C virus (HCV). However, chimpanzee infections with cell culture-derived viruses (JFH1 or related chimeric viruses that replicate efficiently in cell culture) have been limited to acute-transient infections with no pathogenicity. Here, we report persistent infection with chronic hepatitis in a chimpanzee challenged with cell culture-derived genotype 1a virus (H77S.2) containing 6 cell culture-adaptive mutations. Following acute-transient infection with a chimeric H77/JFH1 virus (HJ3-5), intravenous (i.v.) challenge with 10(6) FFU H77S.2 virus resulted in immediate seroconversion and, following an unusual 4- to 6-week delay, persistent viremia accompanied by alanine aminotransferase (ALT) elevation, intrahepatic innate immune responses, and diffuse hepatopathy. This first persistent infection with cell culture-produced HCV provided a unique opportunity to assess evolution of cell culture-adapted virus in vivo. Synonymous and nonsynonymous nucleotide substitution rates were greatest during the first 8 weeks of infection. Of 6 cell culture-adaptive mutations in H77S.2, Q1067R (NS3) had reverted to Q1067 and S2204I (NS5A) was replaced by T2204 within 8 weeks of infection. By 62 weeks, 4 of 6 mutations had reverted to the wild-type sequence, and all reverted to the wild-type sequence by 194 weeks. The data suggest H77S.2 virus has greater potential for persistence and pathogenicity than JFH1 and demonstrate both the capacity of a nonfit virus to persist for weeks in the liver in the absence of detectable viremia as well as strong selective pressure against cell culture-adaptive mutations in vivo. This study shows that mutations promoting the production of infectious genotype 1a HCV in cell culture have the opposite effect and attenuate replication in the liver of the only fully permissive animal species other than humans. It provides the only example to date of persistent infection in a chimpanzee challenged with cell

  9. A new model of Hantaan virus persistence in mice: the balance between HTNV infection and CD8+ T-cell responses

    International Nuclear Information System (INIS)

    Araki, Koichi; Yoshimatsu, Kumiko; Lee, Byoung-Hee; Kariwa, Hiroaki; Takashima, Ikuo; Arikawa, Jiro

    2004-01-01

    We established a viral persistence model that involves the adoptive transfer of spleen cells from immunocompetent mice (H-2 d ) into Hantaan virus (HTNV)-infected severe combined immunodeficient (SCID, H-2 d ) mice. The infection is maintained despite the presence of neutralizing antibodies, without apparent signs of disease, and there is a correlation between HTNV persistence and the lack of HTNV-specific CD8 + T cells. In addition, disseminated HTNV infection before the initiation of immune responses appears to be important for virus persistence. The suppression of HTNV-specific CD8 + T cells in the present model appears to occur at the periphery. The present study also demonstrates that CD8 + T cells contribute to the clearance of HTNV. Thus, it seems that HTNV-specific CD8 + T cells play a key role in HTNV persistence in mice. This model of viral persistence is useful for studies of immune responses and immunocytotherapy against viral infection

  10. Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by (Z-4-bromo-5-(bromomethylene-3-methylfuran-2(5H-one.

    Directory of Open Access Journals (Sweden)

    Jiachuan Pan

    Full Text Available BACKGROUND: Bacteria are well known to form dormant persister cells that are tolerant to most antibiotics. Such intrinsic tolerance also facilitates the development of multidrug resistance through acquired mechanisms. Thus persister cells are a promising target for developing more effective methods to control chronic infections and help prevent the development of multidrug-resistant bacteria. However, control of persister cells is still an unmet challenge. METHODOLOGY/PRINCIPAL FINDINGS: We show in this report that (Z-4-bromo-5-(bromomethylene-3-methylfuran-2(5H-one (BF8 can restore the antibiotic susceptibility of Pseudomonas aeruginosa PAO1 persister cells at growth non-inhibitory concentrations. Persister control by BF8 was found to be effective against both planktonic and biofilm cells of P. aeruginosa PAO1. Interestingly, although BF8 is an inhibitor of quorum sensing (QS in Gram-negative bacteria, the data in this study suggest that the activities of BF8 to revert antibiotic tolerance of P. aeruginosa PAO1 persister cells is not through QS inhibition and may involve other targets. CONCLUSION: BF8 can sensitize P. aeruginosa persister cells to antibiotics.

  11. Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren’s syndrome

    Science.gov (United States)

    2014-01-01

    Introduction Subjects with primary Sjögren’s syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab. Methods To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. Results Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection. Conclusions For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an

  12. The First Year of College: Understanding Student Persistence in Engineering

    OpenAIRE

    Hayden, Marina Calvet

    2017-01-01

    This research study aimed to expand our understanding of the factors that influence student persistence in engineering. The unique experiences of engineering students were examined as they transitioned into and navigated their first year of college at a public research university in California. Most students provided similar responses with respect to the way they experienced the transition to college and social life. There was, however, wide student response variation regarding their experien...

  13. Human T cell aging and the impact of persistent viral infections

    Directory of Open Access Journals (Sweden)

    Tamas eFulop

    2013-09-01

    Full Text Available Aging is associated with a dysregulation of the immune response, loosely termed immunosenescence. Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV, which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.

  14. Persistent renal cortical scintigram defects in children 2 years after urinary tract infection

    International Nuclear Information System (INIS)

    Ditchfield, Michael R.; Cook, David J.; Campo, John F. de; Grimwood, Keith; Powell, Harley R.; Gulati, Sanjeev; Sloane, Robert

    2004-01-01

    Background: Renal cortical scintigraphic studies challenge the role of vesicoureteric reflux in renal scar development, emphasizing instead the part played by acute pyelonephritis. Objective: To determine the prevalence of renal cortical defects in a child cohort 2 years after the child's first diagnosed urinary tract infection and to analyze the relationship of these defects with acute illness variables, primary vesicoureteric reflux and recurrent infections. Materials and methods: In a prospective cohort study, 193 children younger than 5 years with their first proven urinary tract infection underwent renal sonography, voiding cystourethrogram, and renal cortical scintigraphy within 15 days of diagnosis. Two years later, 150 of the 193 children, or 77.7%, had a further renal cortical scintigram, including 75, or 86.2%, of the 87 children who had acute scintigraphic defects. The relationship of cortical defects to age, gender, pre-treatment symptom duration, hospitalization, presence and grade of vesicoureteric reflux, and recurrent urinary tract infections was evaluated. Results: Overall, 20 of the 150 (13.3%; 95% confidence interval (CI) 8.3, 19.8) children had persistent defects 2 years after infection. This included 20 of 75 (26.7%; 95% CI 17.1, 38.1) with initially abnormal scintigrams. No new defects were detected. Although acute defects were more common in the young, those with persistent defects were older (median ages 16.4 vs. 6.8 months, P=0.004) than those with transient abnormalities. After adjustment for age, persistent defects were no longer associated with gender and were not predicted by acute illness variables, primary vesicoureteric reflux or recurrent infections. (orig.)

  15. Survival following salvage abdominoperineal resection for persistent and recurrent squamous cell carcinoma of the anus: do these disease categories affect survival?

    Science.gov (United States)

    Severino, N P; Chadi, S A; Rosen, L; Coiro, S; Choman, E; Berho, M; Wexner, S D

    2016-10-01

    This study aimed to investigate the results of salvage abdominoperineal excision (APR) in patients with persistent or recurrent squamous cell carcinoma of the anus (SCCA). Patients with anal neoplasia were identified from a prospective database. Patients with invasive SCCA with demonstrated failure of chemoradiation therapy (CRT) who underwent salvage APR for one of three disease categories (persistent,  24 months post-CRT) were included. The primary outcome was overall survival after salvage APR. Tumour size, metastatic lymph nodes (LN), circumferential resection margin positivity (CRM) and neurolymphovascular invasion (NLVI) were correlated with the outcome. Thirty-six patients with a median 3-year overall survival of 46% (median follow-up 24 months) underwent salvage APR due to persistent or recurrent SCCA (14 men, mean age 59 years). Eleven (31%) patients were diagnosed with persistent disease, 17 (47%) with early and 8 (22%) with late recurrence. Two-year overall survival of Stage 0/I/II and III/IV disease was 81.5% and 33.74%, respectively (P = 0.022). Overall disease stage was associated with disease categorization (P = 0.009): patients with persistent disease or early recurrence had a significantly higher disease stage than patients with late recurrence (OR = 20.9 and 17.2). Despite apparently improved survival in patients with late disease recurrence on live table analysis, no significant difference was identified in overall survival when stratified by disease category on log-rank test analysis. Persistent and recurrent disease does not show any significant difference in survival, but patients with late recurrence may have a better prognosis. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  16. The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells

    Science.gov (United States)

    Maldiney, Thomas; Bessière, Aurélie; Seguin, Johanne; Teston, Eliott; Sharma, Suchinder K.; Viana, Bruno; Bos, Adrie J. J.; Dorenbos, Pieter; Bessodes, Michel; Gourier, Didier; Scherman, Daniel; Richard, Cyrille

    2014-04-01

    Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.

  17. Altered T cell memory and effector cell development in chronic lymphatic filarial infection that is independent of persistent parasite antigen.

    Directory of Open Access Journals (Sweden)

    Cathy Steel

    2011-04-01

    Full Text Available Chronic lymphatic filarial (LF infection is associated with suppression of parasite-specific T cell responses that persist even following elimination of infection. While several mechanisms have been implicated in mediating this T cell specific downregulation, a role for alterations in the homeostasis of T effector and memory cell populations has not been explored. Using multiparameter flow cytometry, we investigated the role of persistent filarial infection on the maintenance of T cell memory in patients from the filarial-endemic Cook Islands. Compared to filarial-uninfected endemic normals (EN, microfilaria (mf positive infected patients (Inf had a reduced CD4 central memory (T(CM compartment. In addition, Inf patients tended to have more effector memory cells (T(EM and fewer effector cells (T(EFF than did ENs giving significantly smaller T(EFF:T(EM ratios. These contracted T(CM and T(EFF populations were still evident in patients previously mf+ who had cleared their infection (CLInf. Moreover, the density of IL-7Rα, necessary for T memory cell maintenance (but decreased in T effector cells, was significantly higher on memory cells of Inf and CLInf patients, although there was no evidence for decreased IL-7 or increased soluble IL7-Rα, both possible mechanisms for signaling defects in memory cells. However, effector cells that were present in Inf and CLInf patients had lower percentages of HLA-DR suggesting impaired function. These changes in T cell populations appear to reflect chronicity of infection, as filarial-infected children, despite the presence of active infection, did not show alterations in the frequencies of these T cell phenotypes. These data indicate that filarial-infected patients have contracted T(CM compartments and a defect in effector cell development, defects that persist even following clearance of infection. The fact that these global changes in memory and effector cell compartments do not yet occur in infected children

  18. Tissue-resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance.

    Science.gov (United States)

    Gebhardt, Thomas; Palendira, Umaimainthan; Tscharke, David C; Bedoui, Sammy

    2018-05-01

    A large proportion of memory T cells disseminated throughout the body are non-recirculating cells whose maintenance and function is regulated by tissue-specific environmental cues. These sessile cells are referred to as tissue-resident memory T (T RM ) cells and similar populations of non-recirculating cells also exist among unconventional T cells and innate lymphocyte cells. The pool of T RM cells is highly diverse with respect to anatomical positioning, phenotype, molecular regulation and effector function. Nevertheless, certain transcriptional programs are shared and appear as important unifying features for the overall population of T RM cells and tissue-resident lymphocytes. It is now widely appreciated that T RM cells are a critical component of our immune defense by acting as peripheral sentinels capable of rapidly mobilizing protective tissue immunity upon pathogen recognition. This function is of particular importance in anatomical sites that are not effectively surveilled by blood-borne memory T cells in absence of inflammation, such as neuronal tissues or epithelial compartments in skin and mucosae. Focusing on the well-characterized subtype of CD8 +  CD69 +  CD103 + T RM cells, we will review current concepts on the generation, persistence and function of T RM cells and will summarize commonly used tools to study these cells. Furthermore, we will discuss accumulating data that emphasize localized T RM responses as an important determinant of tissue homeostasis and immune defense in the context of microbiota-immune interactions, persistent infections and cancer surveillance. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Persistent pulmonary interstitial emphysema in a case of Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Abbey, Pooja; Narula, Mahender K.; Anand, Rama; Chandra, Jagdish

    2014-01-01

    We present the case of a 10-month-old boy with multisystem Langerhans cell histiocytosis showing thin-walled lung cysts along with computed tomography (CT) evidence of persistent pulmonary interstitial emphysema (PPIE), in the absence of pneumothorax or pneumomediastinum. Follow-up CT performed after 6 months demonstrated complete resolution of interstitial emphysema

  20. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation

    Science.gov (United States)

    Merfa, Marcus V.; Niza, Bárbara; Takita, Marco A.; De Souza, Alessandra A.

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis—CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID:27375608

  1. Persistent inflammation and endothelial activation in HIV-1 infected patients after 12 years of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Frederikke F Rönsholt

    Full Text Available The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART.Inflammation and endothelial activation were assessed by measuring levels of immunoglobulins, β2-microglobulin, interleukin (IL 8, tumor necrosis factor α (TNFα, vascular cell adhesion molecule-1 (sVCAM-1, intercellular adhesion molecule-1 (sICAM-1, sE-Selectin, and sP-Selectin.HIV infected patients had higher levels of β2-microglobulin, IL-8, TNFα, and sICAM-1 than uninfected controls, and HIV infected patients lacked correlation between platelet counts and sP-Selectin levels found in uninfected controls.Discrete signs of systemic and vascular inflammation persist even after very long term cART.

  2. Persistent photovoltage in methylammonium lead iodide perovskite solar cells

    Directory of Open Access Journals (Sweden)

    A. Baumann

    2014-08-01

    Full Text Available We herein perform open circuit voltage decay (OCVD measurements on methylammonium lead iodide (CH3NH3PbI3 perovskite solar cells to increase the understanding of the charge carrier recombination dynamics in this emerging technology. Optically pulsed OCVD measurements are conducted on CH3NH3PbI3 solar cells and compared to results from another type of thin-film photovoltaics, namely, the two reference polymer–fullerene bulk heterojunction solar cell devices based on P3HT:PC60BM and PTB7:PC70BM blends. We observe two very different time domains of the voltage transient in the perovskite solar cell with a first drop on a short time scale that is similar to the decay in the studied organic solar cells. However, 65%–70% of the maximum photovoltage persists on much longer timescales in the perovskite solar cell than in the organic devices. In addition, we find that the recombination dynamics in all time regimes are dependent on the starting illumination intensity, which is also not observed in the organic devices. We then discuss the potential origins of these unique behaviors.

  3. In vivo persistence of sister chromatid exchanges (SCE) induced by gamma rays in mouse bone marrow cells

    International Nuclear Information System (INIS)

    Morales-Ramirez, P.; Vallarino-Kelly, T.; Rodriguez-Reyes, R.

    1984-01-01

    The sister chromatid exchange (SCE) frequencies induced in bone marrow cells by in vivo irradiation with gamma rays before or after bromodeoxyuridine (BrdUrd) incorporation were compared. The frequency of SCE at different postirradiation times was also measured in bone marrow cells in vivo, irradiated before BrdUrd incorporation. Increased sensitivity to SCE induction by radiation was found in cells after BrdUrd incorporation for one cycle when compared with cells irradiated before BrdUrd incorporation. The increased SCE frequency persisted for at least 72 hr after the initial irradiation, implying that the gamma ray-induced lesion(s) capable of eliciting an SCE are persistent and cannot be easily repaired

  4. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Kollerova, Silvia; Jouvet, Lionel; Steiner, Ulrich

    Persister cells, cells that can survive antibiotic exposure but lack heritable antibiotic resistance, are assumed to play a crucial role for the evolution of antibiotic resistance. Persistence is a stage associated with reduced metabolic activity. Most previous studies have been done on batch...... even play a more prominent role for the evolution of resistance and failures of medical treatment by antibiotics as currently assumed....

  5. Childhood maltreatment, personality disorders and 3-year persistence of adult alcohol and nicotine dependence in a national sample.

    Science.gov (United States)

    Elliott, Jennifer C; Stohl, Malka; Wall, Melanie M; Keyes, Katherine M; Skodol, Andrew E; Eaton, Nicholas R; Shmulewitz, Dvora; Goodwin, Renee D; Grant, Bridget F; Hasin, Deborah S

    2016-05-01

    Persistent cases of alcohol and nicotine dependence are associated with considerable morbidity and mortality, and are predicted by childhood maltreatment and personality disorders. Our aim was to test whether personality disorders (individually or conjointly) mediate the relationship between childhood maltreatment and the persistence of dependence. Personality disorders, modeled dimensionally, were tested as mediators of the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence in participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who had current alcohol and nicotine dependence in their baseline interview. Individual personality disorders were assessed in separate models. Then, those that were significant were examined jointly in multiple mediator models to determine their total and unique effects. A large, nationally representative US survey. Participants ≥ 18 years who completed baseline and 3-year follow-up NESARC interviews who had baseline alcohol dependence (n = 1172; 68% male) or nicotine dependence (n = 4017; 52.9% male). Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-IV) measures of childhood maltreatment, personality disorders and alcohol/nicotine dependence. Individual models indicated that many personality disorders mediated the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence (each explaining 6-46% of the total effect, Ps Personality disorder symptoms (especially borderline and antisocial) help explain the association between childhood maltreatment and persistent alcohol and nicotine dependence. © 2016 Society for the Study of Addiction.

  6. Persistence of human parvovirus B19 in multipotent mesenchymal stromal cells expressing the erythrocyte P antigen: implications for transplantation

    Science.gov (United States)

    Sundin, Mikael; Lindblom, Anna; Örvell, Claes; Barrett, A.John; Sundberg, Berit; Watz, Emma; Wikman, Agneta; Broliden, Kristina; Le Blanc, Katarina

    2014-01-01

    Multipotent mesenchymal stromal cells (MSC) are used to improve the outcome of hematopoietic stem cell transplantation and in regenerative medicine. However, MSC may harbor persistent viruses that may compromise their clinical benefit. Retrospectively screened, 1 of 20 MSC from healthy donors contained parvovirus B19 (B19) DNA. We found that MSC express the B19 receptor (the globoside P antigen) and a co-receptor (Ku 80), and can transmit B19 to bone marrow cells in vitro, suggesting that the virus can persist in the marrow stroma of healthy individuals. Two stem cell transplant patients received the B19 positive MSC as treatment for graft-versus-host disease. Neither developed viremia nor symptomatic B19 infection. These results demonstrate for the first time that persistent B19 in MSC can infect hematopoietic cells and underscore the importance of monitoring B19 transmission by MSC products. PMID:18804048

  7. Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.

    Science.gov (United States)

    Li, Yibo; Amarachintha, Surya; Wilson, Andrew F; Li, Xue; Du, Wei

    2017-06-18

    Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G 2 /M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.

  8. Highly differentiated, resting gn-specific memory CD8+ T cells persist years after infection by andes hantavirus.

    Directory of Open Access Journals (Sweden)

    Tobias Manigold

    2010-02-01

    Full Text Available In man, infection with South American Andes virus (ANDV causes hantavirus cardiopulmonary syndrome (HCPS. HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America. A case-fatality rate of about 36% together with the absence of successful antiviral therapies urge the development of a vaccine. Although T-cell responses were shown to be critically involved in immunity to hantaviruses in mouse models, no data are available on the magnitude, specificity and longevity of ANDV-specific memory T-cell responses in patients. Using sets of overlapping peptides in IFN-gamma ELISPOT assays, we herein show in 78 Chilean convalescent patients that Gn-derived epitopes were immunodominant as compared to those from the N- and Gc-proteins. Furthermore, while the relative contribution of the N-specific response significantly declined over time, Gn-specific responses remained readily detectable ex vivo up to 13 years after the acute infection. Tetramer analysis further showed that up to 16.8% of all circulating CD3(+CD8(+ T cells were specific for the single HLA-B*3501-restricted epitope Gn(465-473 years after the acute infection. Remarkably, Gn(465-473-specific cells readily secreted IFN-gamma, granzyme B and TNF-alpha but not IL-2 upon stimulation and showed a 'revertant' CD45RA(+CD27(-CD28(-CCR7(-CD127(- effector memory phenotype, thereby resembling a phenotype seen in other latent virus infections. Most intriguingly, titers of neutralizing antibodies increased over time in 10/17 individuals months to years after the acute infection and independently of whether they were residents of endemic areas or not. Thus, our data suggest intrinsic, latent antigenic stimulation of Gn-specific T-cells. However, it remains a major task for future studies to proof this hypothesis by determination of viral antigen in convalescent patients. Furthermore, it remains to be seen whether Gn-specific T

  9. Neuropsychological alterations in mercury intoxication persist several years after exposure.

    Science.gov (United States)

    Zachi, Elaine Cristina; Taub, Anita; Faria, Marcília de Araújo Medrado; Ventura, Dora Fix

    2008-01-01

    Elemental mercury is a liquid toxic metal widely used in industry. Occupational exposure occurs mainly via inhalation. Previously, neuropsychological assessment detected deficits in former workers of a fluorescent lamp plant who had been exposed to elemental mercury vapor and were away from exposure for several years at the time of examination. The purpose of this work was to reexamine these functions after 18 months in order to evaluate their progression. Thirteen participants completed tests of attention, inhibitory control, verbal/visual memory, psychomotor speed, verbal fluency, visuomotor ability, executive function, semantic knowledge, and depression and anxiety inventories on 2 separate occasions. At baseline, the former workers indicated slower psychomotor and information processing speed, verbal spontaneous recall memory impairment, and increased depression and anxiety symptoms compared to controls (Precovery of functions, the neuropsychological effects related to mercury exposure are found to persist for many years.

  10. Interpreting phenotypic antibiotic tolerance and persister cells as evolution via epigenetic inheritance.

    Science.gov (United States)

    Day, Troy

    2016-04-01

    Epigenetic inheritance is the transmission of nongenetic material such as gene expression levels, RNA and other biomolecules from parents to offspring. There is a growing realization that such forms of inheritance can play an important role in evolution. Bacteria represent a prime example of epigenetic inheritance because a large array of cellular components is transmitted to offspring, in addition to genetic material. Interestingly, there is an extensive and growing empirical literature showing that many bacteria can form 'persister' cells that are phenotypically resistant or tolerant to antibiotics, but most of these results are not interpreted within the context of epigenetic inheritance. Instead, persister cells are usually viewed as a genetically encoded bet-hedging strategy that has evolved in response to a fluctuating environment. Here I show, using a relatively simple model, that many of these empirical findings can be more simply understood as arising from a combination of epigenetic inheritance and cellular noise. I therefore suggest that phenotypic drug tolerance in bacteria might represent one of the best-studied examples of evolution under epigenetic inheritance. © 2016 John Wiley & Sons Ltd.

  11. Persistent Encopresis, Enuresis, and Anxiety in a 7-Year-Old Girl.

    Science.gov (United States)

    Nelson, Theodora; Chae, Heekyung; Anbar, Ran D; Stein, Martin T

    2017-10-01

    Sonia is a 7-year-old old girl who was referred to the Developmental-Behavioral Pediatrics Clinic by the Pediatric Urology Clinic because of persistent wetting and soiling behaviors. Since age 3 years, she has had a history of encopresis (and wetting) for which she has seen gastroenterology and urology specialists. The mother reports that Sonia has accidents almost daily, and she is not upset when sitting in her urine or feces. She dislikes going into the bathroom or sitting on the toilet by herself. She participated in a behavior modification program associated with the pediatric urology clinic, which helps children learn healthy voiding habits and achieve continence.Sonia also has anxious behaviors. She bites her nails and chews on her hair or shirt. She is afraid of small spaces such as those between the bed and the wall and needs to have stuffed animals cover them. Other instances that trigger her anxious behaviors include loud noises, having a substitute teacher, being separated from her mother, and going to certain bathrooms or new places. She also has severe tantrums, which involve throwing and breaking objects, kicking, and hitting her head against doors.A cognitive behavioral therapy program was recommended to target anxiety symptoms, in addition to timed toileting after meals and polyethylene glycol. At a clinic visit several months later, symptoms of anxiety, encopresis, and enuresis persisted. Cognitive behavior therapy was continued and sertraline 25 mg was prescribed for anxiety. In addition, she was referred to a pediatrician who specializes in relaxation techniques and hypnotherapy.Sonia showed modest improvement with these interventions. There were fewer episodes of angry outbursts and a decrease in soiling and wetting, but at times, but she continued to have intermittent periods of wetting and soiling and fear of going to the bathroom by herself persisted.(This Challenging Case extends observations reviewed in a previous Challenging Case: J Dev

  12. Integrated cognitive remediation and standard rehabilitation therapy in patients of schizophrenia: persistence after 5years.

    Science.gov (United States)

    Buonocore, Mariachiara; Spangaro, Marco; Bechi, Margherita; Baraldi, Maria Alice; Cocchi, Federica; Guglielmino, Carmelo; Bianchi, Laura; Mastromatteo, Antonella; Bosia, Marta; Cavallaro, Roberto

    2018-02-01

    Cognitive remediation, often used in combination with standard rehabilitation programs, represents the best available tool to treat cognitive impairments in patients with schizophrenia. However, there are still open questions about durability of effects and generalization of cognitive improvements to functional outcome. This study aims to investigate the persistence of both cognitive and functional effects of combined cognitive remediation plus standard rehabilitation interventions, 5years after completion of the intervention, also comparing different durations of the standard rehabilitation. Sixty patients diagnosed with schizophrenia and previously treated with a 6months intervention, consisting of standard rehabilitation plus 3-months of cognitive remediation, either followed by another year of standard rehabilitation or routine psychiatric treatment, were reassessed with neuropsychological and functional measures 5years after the intervention. Results show that cognitive abilities remained stable after 5years in both groups, while functional performance significantly decreased in patients treated with the 6months intervention only. Data thus suggest that cognitive effects persist even after 5years, while a longer standard rehabilitation following the cognitive remediation program may be needed to achieve a stable functional gain. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Translocation of the B cell receptor to lipid rafts is inhibited in B cells from BLV-infected, persistent lymphocytosis cattle

    International Nuclear Information System (INIS)

    Hamilton, Valerie T.; Stone, Diana M.; Cantor, Glenn H.

    2003-01-01

    Bovine leukemia virus (BLV) infection causes a significant polyclonal expansion of CD5 + , IgM+ B lymphocytes known as persistent lymphocytosis (PL) in approximately 30% of infected cattle. There is evidence that this expanded B cell population has altered signaling, and resistance to apoptosis has been proposed as one mechanism of B cell expansion. In human and murine B cells, antigen binding initiates movement of the B cell receptor (BCR) into membrane microdomains enriched in sphingolipids and cholesterol, termed lipid rafts. Lipid rafts include members of the Src-family kinases and exclude certain phosphatases. Inclusion of the BCR into lipid rafts plays an important role in regulation of early signaling events and subsequent antigen internalization. Viral proteins may also influence signaling events in lipid rafts. Here we demonstrate that the largely CD5 + B cell population in PL cattle has different mobilization and internalization of the BCR when compared to the largely CD5-negative B cells in BLV-negative cattle. Unlike B cells from BLV-negative cattle, the BCR in B cells of BLV-infected, PL cattle resists movement into lipid rafts upon stimulation and is only weakly internalized. Expression of viral proteins as determined by detection of the BLV transmembrane (TM) envelope glycoprotein gp30 did not alter these events in cells from PL cattle. This exclusion of the BCR from lipid rafts may, in part, explain signaling differences seen between B cells of BLV-infected, PL, and BLV-negative cattle and the resistance to apoptosis speculated to contribute to persistent lymphocytosis

  14. Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Londei, M.; Savill, C.M.; Verhoef, A.; Brennan, F.; Leech, Z.A.; Feldmann, M.; Duance, V.; Maini, R.N.

    1989-01-01

    Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis

  15. Persistence and dynamics of DNA damage signal amplification determined by microcolony formation and live-cell imaging

    International Nuclear Information System (INIS)

    Oka, Yasuyoshi; Yamauchi, Motohiro; Suzuki, Masatoshi; Yamashita, Shunichi; Suzuki, Keiji

    2011-01-01

    Cell cycle checkpoints are essential cellular process protecting the integrity of the genome from DNA damaging agents. In the present study, we developed a microcolony assay, in which normal human diploid fibroblast-like cells exposed to ionizing radiation, were plated onto coverslips at very low density (3 cells/cm 2 ). Cells were grown for up to 3 days, and phosphorylated ataxia-telangiectasia mutated (ATM) at Ser1981 and 53BP1 foci were analyzed as the markers for an amplified DNA damage signal. We observed a dose-dependent increase in the fraction of non-dividing cells, whose increase was compromised by knocking down p53 expression. While large persistent foci were predominantly formed in non-dividing cells, we observed some growing colonies that contained cells with large foci. As each microcolony was derived from a single cell, it appeared that some cells could proliferate with large foci. A live-imaging analysis using hTERT-immortalized normal human diploid cells transfected with the EGFP-tagged 53BP1 gene revealed that the formation of persistent large foci was highly dynamic. Delayed appearance and disappearance of large foci were frequently observed in exposed cells visualized 12-72 hours after X-irradiation. Thus, our results indicate that amplified DNA damage signal could be ignored, which may be explained in part by the dynamic nature of the amplification process. (author)

  16. Genetic relationship of lactation persistency with milk yield, somatic cell score, reproductive traits, and longevity in Slovak Holstein cattle

    OpenAIRE

    Strapáková, Eva; Candrák, Juraj; Strapák, Peter

    2016-01-01

    The objective of this study was to estimate the breeding values (BVs) of lactation persistency, the test day of milk yield, the somatic cell score, reproductive traits (calving interval, days open), longevity in Slovak Holstein dairy cattle. BVs were used for the detection of relationships among the persistency of lactation and other selected traits. Data for the estimation of BVs of milk production and somatic cell score were collected from 855 240 cows. BVs for reproductive t...

  17. Altered growth, differentiation, and responsiveness to epidermal growth factor of human embryonic mesenchymal cells of palate by persistent rubella virus infection

    International Nuclear Information System (INIS)

    Yoneda, T.; Urade, M.; Sakuda, M.; Miyazaki, T.

    1986-01-01

    We previously demonstrated that human embryonic mesenchymal cells derived from the palate (HEMP cells) retain alkaline phosphatase (ALP) content and capacity for collagen synthesis after long-term culture, and their growth is markedly stimulated by epidermal growth factor (EGF). There was a dramatic decrease in ALP content and capacity to synthesize collagen in HEMP cells (HEMP-RV cells) persistently infected with rubella virus (RV). EGF increased ALP activity and decreased collagen synthesis in HEMP cells, whereas EGF showed no effect on these activities in HEMP-RV cells. Growth of HEMP-RV cells was slightly reduced compared with that of HEMP cells. EGF stimulated growth of HEMP cells and to a lesser extent of HEMP-RV cells. Binding of 125 I-EGF to cell-surface receptors in HEMP-RV cells was, to our surprise, twice as much as that in HEMP cells. However, internalization of bound 125 I-EGF in HEMP-RV cells was profoundly diminished. Thus, persistent RV infection causes not only changes in HEMP cell growth and differentiation but a decrease in or loss of HEMP cell responsiveness to EGF. The effects of persistent RV infection on palatal cell differentiation as well as growth may be responsible for the pathogenesis of congenital rubella. Furthermore, since HEMP cells appear to be closely related to osteoblasts, these results suggest a mechanism for RV-induced osseous abnormalities manifested in congenital rubella patients

  18. The First Year of College: Understanding Student Persistence in Engineering

    Science.gov (United States)

    Hayden, Marina Calvet

    This research study aimed to expand our understanding of the factors that influence student persistence in engineering. The unique experiences of engineering students were examined as they transitioned into and navigated their first year of college at a public research university in California. Most students provided similar responses with respect to the way they experienced the transition to college and social life. There was, however, wide student response variation regarding their experience of academic life and academic policies, as well as in their level of pre-college academic preparation and financial circumstances. One key finding was that students' experiences during the first year of college varied widely based on the extent to which they had acquired organizational and learning skills prior to college. The study used a mixed methods approach. Quantitative and qualitative data were collected through an online survey and one-on-one interviews conducted with freshman students near the end of their first year of college. The theoretical foundations of this study included Astin's Theory of Student Involvement and Tinto's Theory of Student Departure. The design of the study was guided by these theories which emphasize the critical importance of student involvement with the academic and social aspects of college during the first year of college.

  19. Variable Persister Gene Interactions with (pppGpp for Persister Formation in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Shuang Liu

    2017-09-01

    Full Text Available Persisters comprise a group of phenotypically heterogeneous metabolically quiescent bacteria with multidrug tolerance and contribute to the recalcitrance of chronic infections. Although recent work has shown that toxin-antitoxin (TA system HipAB depends on stringent response effector (pppGppin persister formation, whether other persister pathways are also dependent on stringent response has not been explored. Here we examined the relationship of (pppGpp with 15 common persister genes (dnaK, clpB, rpoS, pspF, tnaA, sucB, ssrA, smpB, recA, umuD, uvrA, hipA, mqsR, relE, dinJ using Escherichia coli as a model. By comparing the persister levels of wild type with their single gene knockout and double knockout mutants with relA, we divided their interactions into five types, namely A “dependent” (dnaK, recA, B “positive reinforcement” (rpoS, pspF, ssrA, recA, C “antagonistic” (clpB, sucB, umuD, uvrA, hipA, mqsR, relE, dinJ, D “epistasis” (clpB, rpoS, tnaA, ssrA, smpB, hipA, and E “irrelevant” (dnaK, clpB, rpoS, tnaA, sucB, smpB, umuD, uvrA, hipA, mqsR, relE, dinJ. We found that the persister gene interactions are intimately dependent on bacterial culture age, cell concentrations (diluted versus undiluted culture, and drug classifications, where the same gene may belong to different groups with varying antibiotics, culture age or cell concentrations. Together, this study represents the first attempt to systematically characterize the intricate relationships among the different mechanisms of persistence and as such provide new insights into the complexity of the persistence phenomenon at the level of persister gene network interactions.

  20. Neuropsychological alterations in mercury intoxication persist several years after exposure

    Directory of Open Access Journals (Sweden)

    Elaine Cristina Zachi

    Full Text Available Abstract Elemental mercury is a liquid toxic metal widely used in industry. Occupational exposure occurs mainly via inhalation. Previously, neuropsychological assessment detected deficits in former workers of a fluorescent lamp plant who had been exposed to elemental mercury vapor and were away from exposure for several years at the time of examination. Objectives: The purpose of this work was to reexamine these functions after 18 months in order to evaluate their progression. Methods: Thirteen participants completed tests of attention, inhibitory control, verbal/visual memory, psychomotor speed, verbal fluency, visuomotor ability, executive function, semantic knowledge, and depression and anxiety inventories on 2 separate occasions. Results: At baseline, the former workers indicated slower psychomotor and information processing speed, verbal spontaneous recall memory impairment, and increased depression and anxiety symptoms compared to controls (P<0.05. Paired comparisons of neuropsychological functioning within the exposed group at baseline and 1.5 years later showed poorer immediate memory performance (P<0.05. There were no differences on other measures. Conclusions: Although the literature show signs of recovery of functions, the neuropsychological effects related to mercury exposure are found to persist for many years.

  1. Emotional and Behavioral Characteristics over a Six-Year Period in Youths with Persistent and Nonpersistent Dyscalculia

    Science.gov (United States)

    Auerbach, Judith G.; Gross-Tsur, Varda; Manor, Orly; Shalev, Ruth S.

    2008-01-01

    The authors examined behavior problems in a matched sample of 58 youths with persistent dyscalculia (PD) and nonpersistent dyscalculia (NPD). Participants were classified as having dyscalculia at age 10-11 years. Parents completed the Child Behavior Checklist for their children at ages 10-11, 13-14, and 16-17 years, while the youths did so at the…

  2. Persistence of Gulf War oil versus intertidal morphology and sediments - one year later

    International Nuclear Information System (INIS)

    Montello, T.M.; Hayes, M.O.; Michel, J.; Al-Momen, A.H.; Al-Mansi, A.M.; Aurand, D.V.

    1993-01-01

    A study of the persistence of oil in the intertidal habitats of the Saudi Arabian coast was carried out one year after the Gulf war spill in conjunction with the National Oceanic and Atmospheric Administration ship Mt. Mitchell's ROPME Sea Cruise. A total of 10 kilometers of transects were surveyed at 20 stations, representing heavily oiled sheltered beaches, tidal flats, algal mats, halophyte saltmarshes, and mangroves at the heads of bays

  3. Students' Persistence and Academic Success in a First-Year Professional Bachelor Program: The Influence of Students' Learning Strategies and Academic Motivation

    Directory of Open Access Journals (Sweden)

    Gert Vanthournout

    2012-01-01

    Full Text Available The present study explores whether students' learning strategies and academic motivation predict persistence and academic success in the first year of higher education. Freshmen students in a professional bachelor program in teacher education were questioned on their learning strategy use and motivation at the start and at the end of the academic year. Students' learning strategies were assessed using the inventory of learning styles-SV. Motivation was measured using scales from the self-regulation questionnaire and the academic motivation scale. Gender and students' prior education were incorporated as control variables. Logistic regression analyses and general linear modelling were applied to predict persistence and academic success, respectively. In each case a stepwise approach in data analysis was used. Results on persistence indicate that lack of regulation and amotivation at the start of the year are significant predictors. For academic success, results showed that relating and structuring, lack of regulation, and lack of motivation at the end of the year are meaningful predictors. Overall, our study demonstrates that learning strategies and motivation have a moderate explanatory value regarding academic success and persistence, and that these effects remain even after controlling for the influence of background variables.

  4. Listeria monocytogenes switches from dissemination to persistence by adopting a vacuolar lifestyle in epithelial cells

    Science.gov (United States)

    Mitchell, Gabriel

    2017-01-01

    Listeria monocytogenes causes listeriosis, a foodborne disease that poses serious risks to fetuses, newborns and immunocompromised adults. This intracellular bacterial pathogen proliferates in the host cytosol and exploits the host actin polymerization machinery to spread from cell-to-cell and disseminate in the host. Here, we report that during several days of infection in human hepatocytes or trophoblast cells, L. monocytogenes switches from this active motile lifestyle to a stage of persistence in vacuoles. Upon intercellular spread, bacteria gradually stopped producing the actin-nucleating protein ActA and became trapped in lysosome-like vacuoles termed Listeria-Containing Vacuoles (LisCVs). Subpopulations of bacteria resisted degradation in LisCVs and entered a slow/non-replicative state. During the subculture of host cells harboring LisCVs, bacteria showed a capacity to cycle between the vacuolar and the actin-based motility stages. When ActA was absent, such as in ΔactA mutants, vacuolar bacteria parasitized host cells in the so-called “viable but non-culturable” state (VBNC), preventing their detection by conventional colony counting methods. The exposure of infected cells to high doses of gentamicin did not trigger the formation of LisCVs, but selected for vacuolar and VBNC bacteria. Together, these results reveal the ability of L. monocytogenes to enter a persistent state in a subset of epithelial cells, which may favor the asymptomatic carriage of this pathogen, lengthen the incubation period of listeriosis, and promote bacterial survival during antibiotic therapy. PMID:29190284

  5. TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.

    Science.gov (United States)

    Maru, Saumya; Jin, Ge; Schell, Todd D; Lukacher, Aron E

    2017-04-01

    Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 TRM cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of TRM cells in a persistent viral infection.

  6. Characterization of Sendai virus persistently infected L929 cells and Sendai virus pi strain: recombinant Sendai viruses having Mpi protein shows lower cytotoxicity and are incapable of establishing persistent infection

    International Nuclear Information System (INIS)

    Nishio, Machiko; Tsurudome, Masato; Ito, Morihiro; Kawano, Mitsuo; Komada, Hiroshi; Ito, Yasuhiko

    2003-01-01

    It is commonly accepted that the temperature-sensitive phenotype of Sendai virus (SeV) persistently infected cells is caused by the M and/or HN proteins. Expression level of the L, M, HN, and V proteins is extremely low in L929 cells persistently infected with SeVpi (L929/SeVpi cells) incubated at 38 deg. C. The HN protein quickly disappears in L929/SeVpi cells following a temperature shift up to 38 deg. C, and pulse-chase experiments show that the Lpi, HNpi, and Mpi proteins are unstable at 38 deg. C. Following a temperature shift either upward or downward, M protein is translocated into the nucleus and then localizes to the perinuclear region. None of virus-specific polypeptides are detected in the cells primarily infected with SeVpi and incubated at 38 deg. C and virus proteins are not pulse-labeled at 38 deg. C, indicating that temperature-sensitive step is at an early stage of infection. The Mpi protein is transiently located in the nucleus of the SeVpi primarily infected cells. Recombinant SeVs possessing the HNpi or/and Mpi proteins are not temperature-sensitive. The HN protein is expressed at very low levels and the F protein localizes to the perinuclear region in rSeV(Mpi)-infected cells incubated at 38 deg. C for 18 h. rSeVs having the Mpi protein exhibit lower cytotoxicity and are incapable of establishing persistent infection. Amino acid 116 of the Mpi protein is related to the nuclear translocation and lower cytopathogenesis, whereas aa183 is involved in the interaction between M protein and viral glycoproteins

  7. Dualities in persistent (co)homology

    International Nuclear Information System (INIS)

    De Silva, Vin; Morozov, Dmitriy; Vejdemo-Johansson, Mikael

    2011-01-01

    We consider sequences of absolute and relative homology and cohomology groups that arise naturally for a filtered cell complex. We establish algebraic relationships between their persistence modules, and show that they contain equivalent information. We explain how one can use the existing algorithm for persistent homology to process any of the four modules, and relate it to a recently introduced persistent cohomology algorithm. We present experimental evidence for the practical efficiency of the latter algorithm

  8. Microrefugia and species persistence in the Galápagos highlands: A 26,000-year paleoecological perspective.

    Directory of Open Access Journals (Sweden)

    Aaron F Collins

    2013-12-01

    Full Text Available The Galápagos Islands are known to have experienced significant drought during the Quaternary. The loss of mesophytic upland habitats has been suggested to underlie the relatively lower endemism of upland compared with lowland plant assemblages. A fossil pollen record spanning the last 26,000 years from an upland bog on Santa Cruz Island, revealed the persistent presence of highland pollen and spore types during the last glacial maximum and a millennial-scale series of droughts in the mid Holocene. The absence of lowland taxa and presence of mesic taxa led to the conclusion that the highland flora of the Galápagos persisted during both these periods. The resiliency of the highland flora of the Galápagos to long-term drought contradicts an earlier hypothesis that an extinction of highland taxa occurred during the last glacial maximum and that rapid Holocene speciation created the modern plant assemblage within the last 10,000 years. Based on the palynological data, we suggest that, even during the height of glacial and Holocene droughts, cool sea-surface temperatures and strong trade-wind activity would have promoted persistent ground level cloudiness that provided the necessary moisture inputs to maintain microrefugia for mesophytic plants. Although moist conditions were maintained, the lack of precipitation caused the loss of open water habitat during such events, and accounts for the known extinctions of species such as Azolla sp., and Elatine sp., while other moisture dependent taxa, i.e. Cyathea weatherbyana, persisted.

  9. Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice

    International Nuclear Information System (INIS)

    Nakamura, Takeshi; Miyagawa, Shinichi; Katsu, Yoshinao; Watanabe, Hajime; Mizutani, Takeshi

    2012-01-01

    Proliferation and differentiation of cells in female reproductive organs, the oviduct, uterus and vagina, are regulated by endogenous estrogen. In utero exposure to a synthetic estrogen, diethylstilbestrol (DES), induces vaginal clear-cell adenocarcinoma in humans. In mice, perinatal exposure to DES results in abnormalities such as polyovular follicles, uterine circular muscle disorganization and persistent vaginal epithelial cell proliferation. We reported the persistent gene expression change such as interleukin-1 (IL-1) related genes, insulin-like growth factor-I (IGF-I) and its downstream signaling in the mouse vagina exposed neonatally to DES. In this study, we found persistent up-regulation of Wnt4 and persistent down-regulation of Wnt11 in the vagina of mice exposed neonatally to DES and estrogen receptor α specific ligand. Also Wnt4 expression in vagina is correlated to the stratification of epithelial cells with the superficial keratinization of vagina, but not epithelial cell stratification only.

  10. Persistence Characteristics of Australian Rainfall Anomalies

    Science.gov (United States)

    Simmonds, Ian; Hope, Pandora

    1997-05-01

    Using 79 years (1913-1991) of Australian monthly precipitation data we examined the nature of the persistence of rainfall anomalies. Analyses were performed for four climate regions covering the country, as well as for the entire Australian continent. We show that rainfall over these regions has high temporal variability and that annual rainfall amounts over all five sectors vary in phase and are, with the exception of the north-west region, significantly correlated with the Southern Oscillation Index (SOI). These relationships were particularly strong during the spring season.It is demonstrated that Australian rainfall exhibits statistically significant persistence on monthly, seasonal, and (to a limited extent) annual time-scales, up to lags of 3 months and one season and 1 year. The persistence showed strong seasonal dependence, with each of the five regions showing memory out to 4 or 5 months from winter and spring. Many aspects of climate in the Australasian region are known to have undergone considerable changes about 1950. We show this to be true for persistence also; its characteristics identified for the entire record were present during the 1951--1980 period, but virtually disappeared in the previous 30-year period.Much of the seasonal distribution of rainfall persistence on monthly time-scales, particularly in the east, is due to the influence of the SOI. However, most of the persistence identified in winter and spring in the north-west is independent of the ENSO phenomenon.Rainfall anomalies following extreme dry and wet months, seasons and years (lowest and highest two deciles) persisted more than would be expected by chance. For monthly extreme events this was more marked in the winter semester for the wet events, except in the south-east region. In general, less persistence was found for the extreme seasons. Although the persistence of dry years was less than would have been expected by chance, the wet years appear to display persistence.

  11. Factors involved in the persistence of stress urinary incontinence from pregnancy to 2 years post partum.

    Science.gov (United States)

    Arrue, Miren; Diez-Itza, Irene; Ibañez, Larraitz; Paredes, Jone; Murgiondo, Arantzazu; Sarasqueta, Cristina

    2011-12-01

    To identify factors involved in the persistence of stress urinary incontinence (SUI) from pregnancy to 2 years post partum. In a longitudinal study at Donostia Hospital, San Sebastián, Spain, 458 primigravid women were recruited from April to October 2007. SUI was diagnosed via the 2002 International Continence Society definition. Severity was assessed via the Incontinence Severity Index, and impact on quality of life via the International Consultation on Incontinence Questionnaire. Means (Student t test and analysis of variance) and percentages (χ(2) and Fisher exact tests) were compared, and multiple logistic regression analysis was performed with variables that were significant or close to significant in a univariate analysis (Ppregnancy. Incontinence severity was slight or moderate in most cases and the impact on quality of life was low. A higher body mass index (BMI) in pregnant women at term was the only factor found to be associated with persistent SUI (odds ratio 1.19; 95% confidence interval 1.08-1.32). Higher BMI in pregnant women at term was an independent risk factor for the persistence of SUI from pregnancy to 2 years post partum. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Persister formation in Staphylococcus aureus is associated with ATP depletion

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian P.; Rowe, Sarah E.; Gandt, Autumn Brown; Nuxoll, Austin S.; Donegan, Niles P.; Zalis, Eliza A.; Clair, Geremy; Adkins, Joshua N.; Cheung, Ambrose L.; Lewis, Kim

    2016-04-18

    Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic bacterial infection and antibiotic treatment failure. In Escherichia coli, toxin/antitoxin (TA) modules are responsible for persister formation. The mechanism of persister formation in Gram positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting TA modules in S. aureus did not affect the level of persisters. Here we show that S. aureus persisters are produced due to a stochastic entrance to stationary phase accompanied by a drop in intracellular ATP. Cells expressing stationary state markers are present throughout the growth phase, increasing in frequency with cell density. Cell sorting revealed that expression of stationary markers was associated with a 100-1000 fold increased likelihood of survival to antibiotic challenge. We find that the antibiotic tolerance of these cells is due to a drop in intracellular ATP. The ATP level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotic treatment.

  13. Persistence of sister chromatid exchanges and in vitro morphological transformation of Syrian hamster fetal cells by chemical and physical carcinogens

    International Nuclear Information System (INIS)

    Popescu, N.C.; Amsbaugh, S.C.; DiPaolo, J.A.

    1985-01-01

    The induction of neoplastic cell transformation is closely associated with DNA alterations which occur shortly after carcinogen exposure. Sister chromatid exchange (SCE) formation is a sensitive indicator of carcinogen-DNA interaction and correlates with the induction of morphological cell transformation. The persistence of lesions generating SCE produced by chemical and physical carcinogens and its relevance to the induction of morphologic transformation was evaluated in coordinated experiments with cultured Syrian hamster fetal cells (HFC). Exponentially growing HFC were exposed for 1 h to benzo[a]pyrene (BP), methyl-methanesulfonate (MMS), cis-platinum (II) diaminedichloride (cis Pt II), N-methyl-N'-nitrosourea (MNU), mitomycin C (MMC), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-acetoxy-2-fluorenyl-acetamide (AcAAF) or u.v. light irradiated. SCE analysis demonstrates that for a period of 48 h after carcinogen exposure, during which time the cells undergo at least four replicative cycles, DNA damage generating SCE induced by all chemical carcinogens either persisted or was partially removed, whereas u.v.-induced lesions were completely removed. An elevated SCE frequency persisted after two additional cell cycles after treatment with BP, AcAAF or MMC without increased cell lethality as compared to other carcinogens whose lesions were completely eliminated during the same period

  14. A case of persistent Müllerian duct syndrome with sertoli cell tumor and hydrometra in a dog.

    Science.gov (United States)

    Matsuu, Aya; Hashizume, Takuya; Kanda, Teppei; Nagano, Masashi; Sugiyama, Akihiko; Okamoto, Yoshiharu; Hikasa, Yoshiaki

    2009-03-01

    A 10-year-old Miniature Schnauzer with bilateral cryptorchidism and male external genitalia was referred with a history of abdominal enlargement. Upon exploratory laparotomy, two tumors and a connecting structure similar to fluid-filled uterus were recognized. After cytological and bacterial examinations of the fluid and histological examination, this dog was diagnosed with bilateral Sertoli cell tumor with hydrometra. The karyotype of this dog was 78, XY and the sry gene was detected positive by PCR. We diagnosed this dog as a case of persistent Müllerian duct syndrome (PMDS), which is male pseudohermaphroditism. This is the first report regarding the incidence of PMDS in Miniature Schnauzers in Japan, and it suggests the involvement of a gene carrier.

  15. Pilot study of a cell phone-based exercise persistence intervention post-rehabilitation for COPD

    Directory of Open Access Journals (Sweden)

    Huong Q Nguyen

    2009-08-01

    Full Text Available Huong Q Nguyen1, Dawn P Gill1, Seth Wolpin1, Bonnie G Steele2, Joshua O Benditt11University of Washington, seattle, WA, USA; 2VA Puget Sound Health Care System, Seattle, WA, USAObjective: To determine the feasibility and efficacy of a six-month, cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease (COPD following pulmonary rehabilitation.Methods: Participants who completed a two-week run-in were randomly assigned to either MOBILE-Coached (n = 9 or MOBILE-Self-Monitored (n = 8. All participants met with a nurse to develop an individualized exercise plan, were issued a pedometer and exercise booklet, and instructed to continue to log their daily exercise and symptoms. MOBILE-Coached also received weekly reinforcement text messages on their cell phones; reports of worsening symptoms were automatically flagged for follow-up. Usability and satisfaction were assessed. Participants completed incremental cycle and six minute walk (6MW tests, wore an activity monitor for 14 days, and reported their health-related quality of life (HRQL at baseline, three, and six months.Results: The sample had a mean age of 68 ± 11 and forced expiratory volume in one second (FEV1 of 40 ± 18% predicted. Participants reported that logging their exercise and symptoms was easy and that keeping track of their exercise helped them remain active. There were no differences between groups over time in maximal workload, 6MW distance, or HRQL (p > 0.05; however, MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months (p = 0.04.Conclusions: We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring. The latter finding needs to be interpreted with caution since this was a purely exploratory study.Trial registration: Clinical

  16. TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.

    Directory of Open Access Journals (Sweden)

    Saumya Maru

    2017-04-01

    Full Text Available Establishing functional tissue-resident memory (TRM cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 TRM cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of TRM cells in a persistent viral infection.

  17. The Immunomodulator VacA Promotes Immune Tolerance and Persistent Helicobacter pylori Infection through Its Activities on T-Cells and Antigen-Presenting Cells

    OpenAIRE

    Djekic, Aleksandra; M?ller, Anne

    2016-01-01

    VacA is a pore-forming toxin that has long been known to induce vacuolization in gastric epithelial cells and to be linked to gastric disorders caused by H. pylori infection. Its role as a major colonization and persistence determinant of H. pylori is less well-understood. The purpose of this review is to discuss the various target cell types of VacA and its mechanism of action; specifically, we focus on the evidence showing that VacA targets myeloid cells and T-cells to directly and indirect...

  18. Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Trovo, Marco; Minatel, Emilio; Durofil, Elena; Polesel, Jerry; Avanzo, Michele; Baresic, Tania; Bearz, Alessandra; Del Conte, Alessandro; Franchin, Giovanni; Gobitti, Carlo; Rumeileh, Imad Abu; Trovo, Mauro G.

    2014-01-01

    Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern

  19. Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Minatel, Emilio; Durofil, Elena [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Polesel, Jerry [Department of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Avanzo, Michele [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Aviano, Pordenone (Italy); Franchin, Giovanni; Gobitti, Carlo; Rumeileh, Imad Abu; Trovo, Mauro G. [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy)

    2014-04-01

    Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.

  20. [Persistent diarrhea

    Science.gov (United States)

    Andrade, J A; Moreira, C; Fagundes Neto, U

    2000-07-01

    INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding.

  1. Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination.

    Science.gov (United States)

    Díez-Domingo, Javier; Baldó, José-María; Planelles-Catarino, Maria Victoria; Garcés-Sánchez, María; Ubeda, Isabel; Jubert-Rosich, Angels; Marès, Josep; Garcia-Corbeira, Pilar; Moris, Philippe; Teko, Maurice; Vanden Abeele, Carline; Gillard, Paul

    2015-03-01

    An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3-9 years. In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3-9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03A or AS03B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. (NCT00502593). The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4(+) T cells with a TH 1 profile were observed. Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  2. The role of metabolism in bacterial persistence

    Directory of Open Access Journals (Sweden)

    Stephanie M. Amato

    2014-03-01

    Full Text Available Bacterial persisters are phenotypic variants with extraordinary tolerances toward antibiotics. Persister survival has been attributed to inhibition of essential cell functions during antibiotic stress, followed by reversal of the process and resumption of growth upon removal of the antibiotic. Metabolism plays a critical role in this process, since it participates in the entry, maintenance, and exit from the persister phenotype. Here, we review the experimental evidence that demonstrates the importance of metabolism to persistence, highlight the successes and potential for targeting metabolism in the search for anti-persister therapies, and discuss the current methods and challenges to understand persister physiology.

  3. Combined effects of PEG hydrogel elasticity and cell-adhesive coating on fibroblast adhesion and persistent migration.

    Science.gov (United States)

    Missirlis, Dimitris; Spatz, Joachim P

    2014-01-13

    The development and use of synthetic, cross-linked, macromolecular substrates with tunable elasticity has been instrumental in revealing the mechanisms by which cells sense and respond to their mechanical microenvironment. We here describe a hydrogel based on radical-free, cross-linked poly(ethylene glycol) to study the effects of both substrate elasticity and type of adhesive coating on fibroblast adhesion and migration. Hydrogel elasticity was controlled through the structure and concentration of branched precursors, which efficiently react via Michael-type addition to produce the polymer network. We found that cell spreading and focal adhesion characteristics are dependent on elasticity for all types of coatings (RGD peptide, fibronectin, vitronectin), albeit with significant differences in magnitude. Importantly, fibroblasts migrated slower but more persistently on stiffer hydrogels, with the effects being more pronounced on fibronectin-coated substrates. Therefore, our results validate the hydrogels presented in this study as suitable for future mechanosensing studies and indicate that cell adhesion, polarity, and associated migration persistence are tuned by substrate elasticity and biochemical properties.

  4. Persistent impacts to the deep soft-bottom benthos one year after the Deepwater Horizon event.

    Science.gov (United States)

    Montagna, Paul A; Baguley, Jeffrey G; Cooksey, Cynthia; Hyland, Jeffrey L

    2017-03-01

    In fall 2010, several months after the Deepwater Horizon blowout was capped, zones of moderate and severe impacts to deep-sea, soft-bottom benthos were identified that together extended over an area of 172 km 2 . A subset of stations sampled in 2010 was resampled in May and June 2011, 10 to 11 months after the event, to determine whether the identified adverse effects were persisting. The design compared 20 stations from the combined moderate and severe impact zone to 12 stations in the reference zone that were sampled in both years. There were no statistically significant differences in contaminant concentrations between the impact and nonimpact zones from 2010 to 2011, which indicates contaminants persisted after 1 y. Whereas there were some signs of recovery in 2011 (particularly for the meiofauna abundance and diversity), there was evidence of persistent, statistically significant impacts to both macrofauna and meiofauna community structure. Macrofaunal taxa richness and diversity in 2011 were still 22.8% and 35.9% less, respectively, in the entire impact zone than in the surrounding nonimpact area, and meiofaunal richness was 28.5% less in the entire impact zone than in the surrounding area. The persistence of significant biodiversity losses and community structure change nearly 1 y after the wellhead was capped indicates that full recovery had yet to have occurred in 2011. Integr Environ Assess Manag 2017;13:342-351. © 2016 SETAC. © 2016 SETAC.

  5. [Vaccination against viral hepatitis A and B in adults aged over 40 years--antibody persistence and immune memory].

    Science.gov (United States)

    Chlibek, R; Smetana, J; Bostíková, V; Splino, M

    2011-09-01

    Primary vaccination with combined vaccine against viral hepatitis A (VHA) and viral hepatitis B (VHB) induces higher anti-hepatitis B surface (anti-HBs) antibody responses and similar anti-hepatitis A virus (anti-HAV) antibody responses in adults aged over 40 years in comparison with concomitant monovalent vaccines against VHA and VHB. Th e objectives were to assess, in a clinical study, persistence of anti-HAV and anti-HBs antibodies in adults aged over 40 years four years after primary VHA/VHB vaccination and antibody response following a booster dose of the vaccine. Five hundred and ninety-six subjects aged > 40 years were vaccinated with three doses of the combined VHA/VHB vaccine at Months 0, 1, 6 (HAB group) or with concomitant VHA and VHB vaccines at Months 0, 6 and 0, 1, 6 (ENG+HAV and HBVX+VAQ, respectively). Blood samples were collected one month following primary vaccination (Month 7) and then at one-year intervals for four years after the booster dose with the same vaccine as used for the primary vaccination. The anti-HBs and anti-HAV antibody levels were determined prior to the booster dose and at days 14 and 30 after the booster dose. At Month 7, > 97% of study subjects were seropositive for anti-HAV antibodies in all groups analyzed. Four years after primary vaccination, anti-HAV antibody seropositivity persisted in > 93% of study subjects, increasing to > 99% after the booster dose. At Month 7, the highest proportion of study subjects with anti-HBs antibody levels > or = 10 mIU/ml was found in the HAB group (91.7% versus 79.7% in the ENG+HAV group versus 71.0% in the HBVX+VAQ group). Four years after vaccination, anti-HBs antibody levels of 10 mIU/ml persisted in 57.1% of the HAB study subjects in comparison with 40.1% and 26.6% of the study subjects in the ENG+HAV and HBVX+VAQ groups, respectively. One month after the booster dose, anti-HBs antibody levels increased and antibody levels > or = 10 mIU/ml was achived in 95.2% of study subjects in the

  6. Effect of Apoptotic Cell Recognition on Macrophage Polarization and Mycobacterial Persistence

    Science.gov (United States)

    de Oliveira Fulco, Tatiana; Andrade, Priscila Ribeiro; de Mattos Barbosa, Mayara Garcia; Pinto, Thiago Gomes Toledo; Ferreira, Paula Fernandez; Ferreira, Helen; da Costa Nery, José Augusto; Real, Suzana Côrte; Borges, Valéria Matos; Moraes, Milton Ozório; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira

    2014-01-01

    Intracellular Mycobacterium leprae infection modifies host macrophage programming, creating a protective niche for bacterial survival. The milieu regulating cellular apoptosis in the tissue plays an important role in defining susceptible and/or resistant phenotypes. A higher density of apoptotic cells has been demonstrated in paucibacillary leprosy lesions than in multibacillary ones. However, the effect of apoptotic cell removal on M. leprae-stimulated cells has yet to be fully elucidated. In this study, we investigated whether apoptotic cell removal (efferocytosis) induces different phenotypes in proinflammatory (Mϕ1) and anti-inflammatory (Mϕ2) macrophages in the presence of M. leprae. We stimulated Mϕ1 and Mϕ2 cells with M. leprae in the presence or absence of apoptotic cells and subsequently evaluated the M. leprae uptake, cell phenotype, and cytokine pattern in the supernatants. In the presence of M. leprae and apoptotic cells, Mϕ1 macrophages changed their phenotype to resemble the Mϕ2 phenotype, displaying increased CD163 and SRA-I expression as well as higher phagocytic capacity. Efferocytosis increased M. leprae survival in Mϕ1 cells, accompanied by reduced interleukin-15 (IL-15) and IL-6 levels and increased transforming growth factor beta (TGF-β) and IL-10 secretion. Mϕ1 cells primed with M. leprae in the presence of apoptotic cells induced the secretion of Th2 cytokines IL-4 and IL-13 in autologous T cells compared with cultures stimulated with M. leprae or apoptotic cells alone. Efferocytosis did not alter the Mϕ2 cell phenotype or cytokine secretion profile, except for TGF-β. Based on these data, we suggest that, in paucibacillary leprosy patients, efferocytosis contributes to mycobacterial persistence by increasing the Mϕ2 population and sustaining the infection. PMID:25024361

  7. Understanding effects of matrix protease and matrix organization on directional persistence and translational speed in three-dimensional cell migration.

    Science.gov (United States)

    Zaman, Muhammad H; Matsudaira, Paul; Lauffenburger, Douglas A

    2007-01-01

    Recent studies have shown significant differences in migration mechanisms between two- and three-dimensional environments. While experiments have suggested a strong dependence of in vivo migration on both structure and proteolytic activity, the underlying biophysics of such dependence has not been studied adequately. In addition, the existing models of persistent random walk migration are primarily based on two-dimensional movement and do not account for the effect of proteolysis or matrix inhomogeneity. Using lattice Monte Carlo methods, we present a model to study the role of matrix metallo-proteases (MMPs) on directional persistence and speed. The simulations account for a given cell's ability to deform as well as to digest the matrix as the cell moves in three dimensions. Our results show a bimodal dependence of speed and persistence on matrix pore size and suggest high sensitivity on MMP activity, which is in very good agreement with experimental studies carried out in 3D matrices.

  8. Compliance and persistence of antidepressants versus anticonvulsants in patients with neuropathic pain during the first year of therapy.

    Science.gov (United States)

    Gharibian, Derenik; Polzin, Jennifer K; Rho, Jay P

    2013-05-01

    Neuropathic pain (NP) is a chronic condition that has human, social, and economic consequences. A variety of agents can be used for treatment; however, antidepressants and anticonvulsants are the 2 classes most widely studied and represent first-line agents in the management of NP. Little information is known about the adherence patterns of these medications during the first year of therapy in patients with NP. To examine the compliance and persistence of antidepressants versus anticonvulsants in patients with NP during the first year of therapy. Using electronic medical and pharmacy data for the Kaiser Permanente Southern California region, the adherence patterns for patients with a NP diagnosis prescribed an antidepressant or an anticonvulsant were studied. Compliance and persistence were measured using the medication possession ratio and the Refill-Sequence model, respectively. The study included 1817 patients with NP diagnosis taking either an antidepressant or an anticonvulsant. Within the antidepressant group, 42.9% were considered compliant, compared with 43.7% in the anticonvulsant group. Subanalysis of the 2 cohorts revealed that patients on venlafaxine were the most compliant (69.4%) compared with patients taking gabapentin (44.4%) and tricyclic antidepressants (41.8%) (Panticonvulsant group were considered persistent with their medication refills. Compliance and persistence rates were similar for patients with NP diagnosis taking antidepressants and anticonvulsants. Higher compliance was observed among patients taking venlafaxine; however, this population did have a small sample size.

  9. Basic Fibroblast Growth Factor Regulates Persistent ERK Osciliations in Premaligant but not Malignant JB6 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Thomas J.; Shankaran, Harish; Wiley, H. S.; Opresko, Lee K.; Chrisler, William B.; Quesenberry, Ryan D.

    2010-05-02

    basic fibroblast growth factor (bFGF or FGF2) plays an important role in epidermal wound healing in vivo and is associated with a persistent increased in the extracellular signal-regulated kinase (ERK) pathway in vitro. Here we have examined whether bFGF induces the closure of an experimental scratch wound in JB6 mouse epidermal cells and have explored the regulation of the ERK pathway by bFGF in the context of kinase oscillations. bFGF stimulation is associated with increases in cellular phospho-ERK and phospho-c-Jun levels. In addition, bFGF increases cell proliferation and a change in cell morphology (stellate appearance) in a dose-dependent fashion (0.1 – 100 ng/ml). bFGF treatment also promoted the closure of an experimental scratch wound in vitro. JB6 cells were stably transfected with an ERK1-GFP chimera to follow temporal ERK subcellular distribution patterns. We observe a persistent upregulation of the ERK pathway, as evidenced by a significant increase in nuclear ERK1-GFP levels at time points up to 24 hr after bFGF treatment. Interestingly, at the single cell level, ERK is observed to oscillate between nuclear and cytosolic compartments in response to bFGF treatment. Because this oscillatory behavior is asynchronous in the cell population, it is only clearly resolved at the single cell level. Collectively, data presented here are consistent with an important role for bFGF in wound healing and suggest a more complex regulation of the ERK pathway by bFGF than has previously been appreciated.

  10. Biosynthesis of measles virus hemagglutinin in persistently infected cells

    International Nuclear Information System (INIS)

    Bellini, W.J.; Silver, G.D.; McFarlin, D.E.

    1983-01-01

    The synthesis of the hemagglutinin (HA) glycoprotein of measles virus was investigated in a persistently infected cell line using a monoclonal anti-HA. The synthesis of the HA protein was shown to be associated with the rough endoplasmic reticulum. The unglycosylated (HA 0 ) apoprotein is synthesized as a 65.000 dalton peptide and is inserted into the rough endoplasmic reticulum as a transmembrane protein with approximately 2 to 3000 daltons of the peptide exposed to the cytoplasmic membrane surface. Primary glycosylation of the HA protein was found to occur through the lipid-linked carrier, dolichol-phosphate, as determined by inhibition of glycosylation by tunicamycin. Glycosylation, however, was not a prerequisite for membrane insertion. Endo-β-N-acetyl-Glucosaminidase H digestion of the fully glycosylated HA protein indicated that both simple and complex oligosaccharides are present on the surface glycoprotein. (Author)

  11. Resting regulatory CD4 T cells: a site of HIV persistence in patients on long-term effective antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Tu-Anh Tran

    Full Text Available BACKGROUND: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs are a CD4+ T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART. METHODOLOGY/PRINCIPAL FINDINGS: We found evidence of infection of resting Tregs (HLADR(-CD69(-CD25(hiFoxP3+CD4+ T cells purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir. CONCLUSIONS: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging.

  12. Persistent expression of BMP-4 in embryonic chick adrenal cortical cells and its role in chromaffin cell development

    Directory of Open Access Journals (Sweden)

    Halbach Oliver

    2008-10-01

    Full Text Available Abstract Background Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate. Results We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of 'chromaffin' granules were significantly increased. Conclusion BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype.

  13. Persistence and drug tolerance in pathogenic yeast

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2017-01-01

    In this review, we briefly summarize the current understanding of how fungal pathogens can persist antifungal treatment without heritable resistance mutations by forming tolerant persister cells. Fungal infections tolerant to antifungal treatment have become a major medical problem. One mechanism...

  14. CD4+ T Cell-derived IL-10 Promotes Brucella abortus Persistence via Modulation of Macrophage Function

    Science.gov (United States)

    Xavier, Mariana N.; Winter, Maria G.; Spees, Alanna M.; Nguyen, Kim; Atluri, Vidya L.; Silva, Teane M. A.; Bäumler, Andreas J.; Müller, Werner; Santos, Renato L.; Tsolis, Renée M.

    2013-01-01

    Evasion of host immune responses is a prerequisite for chronic bacterial diseases; however, the underlying mechanisms are not fully understood. Here, we show that the persistent intracellular pathogen Brucella abortus prevents immune activation of macrophages by inducing CD4+CD25+ T cells to produce the anti-inflammatory cytokine interleukin-10 (IL-10) early during infection. IL-10 receptor (IL-10R) blockage in macrophages resulted in significantly higher NF-kB activation as well as decreased bacterial intracellular survival associated with an inability of B. abortus to escape the late endosome compartment in vitro. Moreover, either a lack of IL-10 production by T cells or a lack of macrophage responsiveness to this cytokine resulted in an increased ability of mice to control B. abortus infection, while inducing elevated production of pro-inflammatory cytokines, which led to severe pathology in liver and spleen of infected mice. Collectively, our results suggest that early IL-10 production by CD25+CD4+ T cells modulates macrophage function and contributes to an initial balance between pro-inflammatory and anti-inflammatory cytokines that is beneficial to the pathogen, thereby promoting enhanced bacterial survival and persistent infection. PMID:23818855

  15. Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis

    International Nuclear Information System (INIS)

    Airaksinen, Antero; Pariente, Nonia; Menendez-Arias, Luis; Domingo, Esteban

    2003-01-01

    BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV) can be cured of virus by treatment with the antiviral nucleoside analogue ribavirin. To study whether the process involved an increase in the number of mutations in the mutant spectrum of the viral population, viral genomes were cloned from persistently infected cells treated or untreated with ribavirin. An increase of up to 10-fold in mutation frequencies associated with ribavirin treatment was observed in the viral genomes from the treated cultures as compared with parallel, untreated cultures. To address the possible mechanisms of enhanced mutagenesis, we investigated the mutagenic effects of ribavirin together with guanosine, and mycophenolic acid in the presence or absence of guanosine. Changes in the intracellular nucleotide concentrations were determined for all treatments. The results suggest that the increased mutation frequencies were not dependent on nucleotide pool imbalances or due to selection of preexisting genomes but they were produced by a mutagenic action of ribavirin

  16. Omalizumab therapy in a 13-year-old boy with severe persistent asthma and concomitant eosinophilic esophagitis.

    Science.gov (United States)

    Arasi, Stefania; Costa, Stefano; Magazzù, Giuseppe; Ieni, Antonio; Crisafulli, Giuseppe; Caminiti, Lucia; Chiera, Fernanda; Vaccaro, Mario; Del Giudice, Michele Miraglia; Pajno, Giovanni Battista

    2016-03-22

    Eosinophilic esophagitis (EoE) has been defined as "asthma of the esophagus" for the large number of similarities between the two diseases. Omalizumab is an anti-Immunoglobulin E (IgE) antibody currently approved only in allergic IgE-mediated severe persistent uncontrolled asthma and in chronic spontaneous urticaria unresponsive to antihistamines, but it has been tried in other diseases, too. We present herein the case of a 13-year-old boy, affected from preschool age by severe chronic allergic asthma poorly controlled despite a generous long-term therapy, and, since he was 8 years old, by eosinophilic esophagitis, responsive to courses of strict elimination diet and semi-elemental diet, even if very burdensome for his quality of life. At the age of 11.5 years, for inadequate asthma control, he started to receive therapy with omalizumab. After the first month and for the entire duration (18 months) of omalizumab treatment, asthma was well controlled, long-term conventional therapy was gradually withdrawn and lung- function improved. Concerning EoE, after an initial clinical but not histological remission during the first few months of treatment with omalizumab, the patient experienced an exacerbation of gastrointestinal symptoms. Therefore, he started treatment with topical steroids which was effective to improve gastrointestinal symptoms. However, EoE is still steroid-dependent. Currently, he continues both treatments: omalizumab for asthma and topical steroid for EoE. This case report confirms that omalizumab is an effective treatment in patients with severe persistent, uncontrolled asthma. On the other hand, in our patient it did not produce persistent improvement neither on symptoms nor on biopsy findings of EoE. The outcome of this case might indicate different pathogenic mechanism(s) of the two diseases.

  17. Deficient incorporation of spike protein into virions contributes to the lack of infectivity following establishment of a persistent, non-productive infection in oligodendroglial cell culture by murine coronavirus

    International Nuclear Information System (INIS)

    Liu Yin; Herbst, Werner; Cao Jianzhong; Zhang Xuming

    2011-01-01

    Infection of mouse oligodendrocytes with a recombinant mouse hepatitis virus (MHV) expressing a green fluorescence protein facilitated specific selection of virus-infected cells and subsequent establishment of persistence. Interestingly, while viral genomic RNAs persisted in infected cells over 14 subsequent passages with concomitant synthesis of viral subgenomic mRNAs and structural proteins, no infectious virus was isolated beyond passage 2. Further biochemical and electron microscopic analyses revealed that virions, while assembled, contained little spike in the envelope, indicating that lack of infectivity during persistence was likely due to deficiency in spike incorporation. This type of non-lytic, non-productive persistence in oligodendrocytes is unique among animal viruses and resembles MHV persistence previously observed in the mouse central nervous system. Thus, establishment of such a culture system that can recapitulate the in vivo phenomenon will provide a powerful approach for elucidating the mechanisms of coronavirus persistence in glial cells at the cellular and molecular levels.

  18. Persistence-Driven Durotaxis: Generic, Directed Motility in Rigidity Gradients

    Science.gov (United States)

    Novikova, Elizaveta A.; Raab, Matthew; Discher, Dennis E.; Storm, Cornelis

    2017-02-01

    Cells move differently on substrates with different rigidities: the persistence time of their motion is higher on stiffer substrates. We show that this behavior—in and of itself—results in a net flux of cells directed up a soft-to-stiff gradient. Using simple random walk models with varying persistence and stochastic simulations, we characterize the propensity to move in terms of the durotactic index also measured in experiments. A one-dimensional model captures the essential features and highlights the competition between diffusive spreading and linear, wavelike propagation. Persistence-driven durokinesis is generic and may be of use in the design of instructive environments for cells and other motile, mechanosensitive objects.

  19. Persistence of Multidrug-Resistant Acinetobacter baumannii Isolates Harboring blaOXA-23 and bap for 5 Years.

    Science.gov (United States)

    Sung, Ji Youn; Koo, Sun Hoe; Kim, Semi; Kwon, Gye Cheol

    2016-08-28

    The emergence and dissemination of carbapenemase-producing Acinetobacter baumannii isolates have been reported worldwide, and A. baumannii isolates harboring blaOXA-23 are often resistant to various antimicrobial agents. Antimicrobial resistance can be particularly strong for biofilm-forming A. baumannii isolates. We investigated the genetic basis for carbapenem resistance and biofilm-forming ability of multidrug-resistant (MDR) clinical isolates. Ninety-two MDR A. baumannii isolates were collected from one university hospital located in the Chungcheong area of Korea over a 5-year period. Multiplex PCR and DNA sequencing were performed to characterize carbapenemase and bap genes. Clonal characteristics were analyzed using REP-PCR. In addition, imaging and quantification of biofilms were performed using a crystal violet assay. All 92 MDR A. baumannii isolates involved in our study contained the blaOXA-23 and bap genes. The average absorbance of biomass in Bap-producing strains was much greater than that in non-Bap-producing strains. In our study, only three REP-PCR types were found, and the isolates showing type A or type B were found more than 60 times among unique patients during the 5 years of surveillance. These results suggest that the isolates have persisted and colonized for 5 years, and biofilm formation ability has been responsible for their persistence and colonization.

  20. High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence.

    Science.gov (United States)

    Damouche, Abderaouf; Pourcher, Guillaume; Pourcher, Valérie; Benoist, Stéphane; Busson, Elodie; Lataillade, Jean-Jacques; Le Van, Mélanie; Lazure, Thierry; Adam, Julien; Favier, Benoit; Vaslin, Bruno; Müller-Trutwin, Michaela; Lambotte, Olivier; Bourgeois, Christine

    2017-12-01

    We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA-DR) could be detected, and the percentage of CD69-expressing resident memory CD4 + T cells was not affected. Overall, our results indicate that adipose-tissue-resident CD4 + T cells are not extensively activated during HIV infection. PD-1 was expressed by a high proportion of tissue-resident memory CD4 + T cells in both HIV-infected patients and non-HIV-infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Tetracapsuloides bryosalmonae persists in brown trout Salmo trutta for five years post exposure.

    Science.gov (United States)

    Soliman, Hatem; Kumar, Gokhlesh; El-Matbouli, Mansour

    2018-01-31

    Tetracapsuloides bryosalmonae is a malacosporean parasite and the causative agent of proliferative kidney disease (PKD) that seriously impacts farmed and wild salmonids. The parasite's life cycle includes an invertebrate host, the bryozoan Fredericella sultana, and a vertebrate host, salmonid fish. The persistence of T. bryosalmonae in brown trout Salmo trutta for up to 2 yr following exposure is well documented. Results from the present study confirmed that one brown trout that had recovered from PKD did not completely clear the parasite from its tissues and that T. bryosalmonae could persist in brown trout for up to 5 yr post exposure. Furthermore, recovered infected brown trout can release viable T. bryosalmonae spores that are able to infect specific pathogen-free F. sultana colonies. T. bryosalmonae DNA was detected by PCR in every organ, and parasite stages were observed in the kidney, spleen and liver following immunohistochemistry. This finding indicates that T. bryosalmonae-infected brown trout can act as asymptomatic carriers and release the parasite for several years after the initial infection, acting as a reservoir of infection, and contributing to the dissemination of the parasite to new areas.

  2. Persistent asthma in adults: comparison of high resolution computed tomography of the lungs after one year of follow-up

    International Nuclear Information System (INIS)

    Cukier, Alberto; Stelmach, Rafael; Kavakama, Jorge Issamu; Terra Filho, Mario; Vargas, Francisco

    2001-01-01

    The aims of this study were to evaluate the role of high resolution computed tomography of the thorax in detecting abnormalities in chronic asthmatic patients and to determine the behavior of these lesions after at least one year. Fourteen persistent asthmatic patients with a mean forced expiratory volume in 1-second that was 63% of predicted and a mean forced expiratory volume in 1-second /forced vital capacity of 60% had two high resolution computed tomography separated by an interval of at least one year. All 14 patients had abnormalities on both scans. The most common abnormality was bronchial wall thickening, which was present in all patients on both computed tomography. Bronchiectasis was suggested on the first computed tomography in 5 of the 14 (36%) patients, but on follow-up, the bronchial dilatation had disappeared in 2 and diminished in a third. Only one patient had any emphysematous changes; a minimal persistent area of para septal emphysema was present on both scans. In 3 patients, a 'mosaic' appearance was observed on the first scan, and this persisted on the follow-up computed tomography. Two patients had persistent areas of mucoid impaction. In a third patient, mucus plugging was detected only on the second computed tomography. We conclude that there are many abnormalities on the high resolution computed tomography of patients with persistent asthma. Changes suggestive of bronchiectasis, namely bronchial dilatation, frequently resolve spontaneously. Therefore, the diagnosis of bronchiectasis by high resolution computed tomography in asthmatic patients must be made with caution, since bronchial dilatation can be reversible or can represent false dilatation. Non smoking chronic asthmatic subjects in this study had no evidence of centrilobular or panacinar emphysema. (author)

  3. The association of the vitamin D status with the persistence of anti-HBs antibody at 20years after primary vaccination with recombinant hepatitis B vaccine in infancy.

    Science.gov (United States)

    Jafarzadeh, A; Keshavarz, J; Bagheri-Jamebozorgi, M; Nemati, M; Frootan, R; Shokri, F

    2017-02-01

    Vitamin D has potent immunoregulatory effects due to the expression of its receptor on the majority of immune cells. The aim was to evaluate the association of the vitamin D status with the persistence of anti-HBs antibody and immune response to booster immunization at 20years after primary vaccination with hepatitis B (HB) vaccine. Blood samples were collected from 300 adults 20years after completion of the primary HB vaccination in infancy. The serum levels of vitamin D and anti-HBs antibody were measured by ELISA. A single booster dose of a recombinant HB vaccine was administered to a total of 138 subjects, whose anti-HBs titer wasanti-HBs antibody, 4weeks after booster vaccination. At 20years after primary vaccination, the mean vitamin D concentrations were significantly higher in seroprotective subjects as compared to non-seroprotective individuals (Panti-HBs were significantly increased with advanced concentrations of vitamin D (PD were significantly higher in subjects with an anamnestic response to booster vaccination as compared with subjects without this response (PD status may influence the persistence of anti-HBs antibody and durability of protection after primary vaccination with a recombinant HB vaccine in infancy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status.

    Science.gov (United States)

    Circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a HoBi-...

  5. T-Cell Therapy Using Interleukin-21-Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression.

    Science.gov (United States)

    Chapuis, Aude G; Roberts, Ilana M; Thompson, John A; Margolin, Kim A; Bhatia, Shailender; Lee, Sylvia M; Sloan, Heather L; Lai, Ivy P; Farrar, Erik A; Wagener, Felecia; Shibuya, Kendall C; Cao, Jianhong; Wolchok, Jedd D; Greenberg, Philip D; Yee, Cassian

    2016-11-01

    Purpose Peripheral blood-derived antigen-specific cytotoxic T cells (CTLs) provide a readily available source of effector cells that can be administered with minimal toxicity in an outpatient setting. In metastatic melanoma, this approach results in measurable albeit modest clinical responses in patients resistant to conventional therapy. We reasoned that concurrent cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) checkpoint blockade might enhance the antitumor activity of adoptively transferred CTLs. Patients and Methods Autologous MART1-specific CTLs were generated by priming with peptide-pulsed dendritic cells in the presence of interleukin-21 and enriched by peptide-major histocompatibility complex multimer-guided cell sorting. This expeditiously yielded polyclonal CTL lines uniformly expressing markers associated with an enhanced survival potential. In this first-in-human strategy, 10 patients with stage IV melanoma received the MART1-specific CTLs followed by a standard course of anti-CTLA-4 (ipilimumab). Results The toxicity profile of the combined treatment was comparable to that of ipilimumab monotherapy. Evaluation of best responses at 12 weeks yielded two continuous complete remissions, one partial response (PR) using RECIST criteria (two PRs using immune-related response criteria), and three instances of stable disease. Infused CTLs persisted with frequencies up to 2.9% of CD8 + T cells for as long as the patients were monitored (up to 40 weeks). In patients who experienced complete remissions, PRs, or stable disease, the persisting CTLs acquired phenotypic and functional characteristics of long-lived memory cells. Moreover, these patients also developed responses to nontargeted tumor antigens (epitope spreading). Conclusion We demonstrate that combining antigen-specific CTLs with CTLA-4 blockade is safe and produces durable clinical responses, likely reflecting both enhanced activity of transferred cells and improved recruitment of new responses

  6. Risk factors for the onset and persistence of neck pain in undergraduate students: 1-year prospective cohort study

    Science.gov (United States)

    2011-01-01

    Background Although neck pain is common in young adulthood, studies on predictive factors for its onset and persistence are scarce. It is therefore important to identify possible risk factors among young adults so as to prevent the development of neck pain later in life. Methods A prospective study was carried out in healthy undergraduate students. At baseline, a self-administered questionnaire and standardized physical examination were used to collect data on biopsychosocial factors. At 3, 6, 9, and 12 months thereafter, follow-up data were collected on the incidence of neck pain. Those who reported neck pain on ≥ 2 consecutive follow-ups were categorized as having persistent neck pain. Two regression models were built to analyze risk factors for the onset and persistence of neck pain. Results Among the recruited sample of 684 students, 46% reported the onset of neck pain between baseline and 1-year follow-up, of whom 33% reported persistent neck pain. The onset of neck pain was associated with computer screen position not being level with the eyes and mouse position being self-rated as suitable. Factors that predicted persistence of neck pain were position of the keyboard being too high, use of computer for entertainment Neck pain is quite common among undergraduate students. This study found very few proposed risk factors that predicted onset and persistence of neck pain. The future health of undergraduate students deserves consideration. However, there is still much uncertainty about factors leading to neck pain and more research is needed on this topic. PMID:21756362

  7. Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Tobias Dörr

    2010-02-01

    Full Text Available Bacteria induce stress responses that protect the cell from lethal factors such as DNA-damaging agents. Bacterial populations also form persisters, dormant cells that are highly tolerant to antibiotics and play an important role in recalcitrance of biofilm infections. Stress response and dormancy appear to represent alternative strategies of cell survival. The mechanism of persister formation is unknown, but isolated persisters show increased levels of toxin/antitoxin (TA transcripts. We have found previously that one or more components of the SOS response induce persister formation after exposure to a DNA-damaging antibiotic. The SOS response induces several TA genes in Escherichia coli. Here, we show that a knockout of a particular SOS-TA locus, tisAB/istR, had a sharply decreased level of persisters tolerant to ciprofloxacin, an antibiotic that causes DNA damage. Step-wise administration of ciprofloxacin induced persister formation in a tisAB-dependent manner, and cells producing TisB toxin were tolerant to multiple antibiotics. TisB is a membrane peptide that was shown to decrease proton motive force and ATP levels, consistent with its role in forming dormant cells. These results suggest that a DNA damage-induced toxin controls production of multidrug tolerant cells and thus provide a model of persister formation.

  8. Persistent genital herpes simplex virus-2 shedding years following the first clinical episode.

    Science.gov (United States)

    Phipps, Warren; Saracino, Misty; Magaret, Amalia; Selke, Stacy; Remington, Mike; Huang, Meei-Li; Warren, Terri; Casper, Corey; Corey, Lawrence; Wald, Anna

    2011-01-15

    Patients with newly acquired genital herpes simplex virus 2 (HSV-2) infection have virus frequently detected at the genital mucosa. Rates of genital shedding initially decrease over time after infection, but data on long-term viral shedding are lacking. For this study, 377 healthy adults with history of symptomatic genital HSV-2 infection collected anogenital swabs for HSV-2 DNA polymerase chain reaction for at least 30 consecutive days. Time since first genital herpes episode was significantly associated with reduced genital shedding. Total HSV shedding occurred on 33.6% of days in participants <1 year, 20.6% in those 1-9 years, and 16.7% in those ≥10 years from first episode. Subclinical HSV shedding occurred on 26.2% of days among participants <1 year, 13.1% in those 1-9 years, and 9.3% in those ≥10 years from first episode. On days with HSV detection, mean quantity was 4.9 log₁₀ copies/mL for those <1 year, 4.7 log₁₀ copies/mL among those 1-9 years, and 4.6 log₁₀ copies/mL among those ≥10 years since first episode. Rates of total and subclinical HSV-2 shedding decrease after the first year following the initial clinical episode. However, viral shedding persists at high rates and copy numbers years after infection, and therefore may pose continued risk of HSV-2 transmission to sexual partners.

  9. T-Cell Therapy Using Interleukin-21–Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression

    Science.gov (United States)

    Chapuis, Aude G.; Roberts, Ilana M.; Thompson, John A.; Margolin, Kim A.; Bhatia, Shailender; Lee, Sylvia M.; Sloan, Heather L.; Lai, Ivy P.; Farrar, Erik A.; Wagener, Felecia; Shibuya, Kendall C.; Cao, Jianhong; Wolchok, Jedd D.; Greenberg, Philip D.

    2016-01-01

    Purpose Peripheral blood–derived antigen-specific cytotoxic T cells (CTLs) provide a readily available source of effector cells that can be administered with minimal toxicity in an outpatient setting. In metastatic melanoma, this approach results in measurable albeit modest clinical responses in patients resistant to conventional therapy. We reasoned that concurrent cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) checkpoint blockade might enhance the antitumor activity of adoptively transferred CTLs. Patients and Methods Autologous MART1-specific CTLs were generated by priming with peptide-pulsed dendritic cells in the presence of interleukin-21 and enriched by peptide-major histocompatibility complex multimer-guided cell sorting. This expeditiously yielded polyclonal CTL lines uniformly expressing markers associated with an enhanced survival potential. In this first-in-human strategy, 10 patients with stage IV melanoma received the MART1-specific CTLs followed by a standard course of anti–CTLA-4 (ipilimumab). Results The toxicity profile of the combined treatment was comparable to that of ipilimumab monotherapy. Evaluation of best responses at 12 weeks yielded two continuous complete remissions, one partial response (PR) using RECIST criteria (two PRs using immune-related response criteria), and three instances of stable disease. Infused CTLs persisted with frequencies up to 2.9% of CD8+ T cells for as long as the patients were monitored (up to 40 weeks). In patients who experienced complete remissions, PRs, or stable disease, the persisting CTLs acquired phenotypic and functional characteristics of long-lived memory cells. Moreover, these patients also developed responses to nontargeted tumor antigens (epitope spreading). Conclusion We demonstrate that combining antigen-specific CTLs with CTLA-4 blockade is safe and produces durable clinical responses, likely reflecting both enhanced activity of transferred cells and improved recruitment of new responses

  10. Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+ Tissue-Resident Memory T Cells

    Directory of Open Access Journals (Sweden)

    Tessa Bergsbaken

    2017-04-01

    Full Text Available Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8+ T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103−CD69+ Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN-β and interleukin-12 (IL-12, which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103−CD69+ Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2+ IL-12-producing cells reduced the size of the CD103− Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity.

  11. Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine.

    Science.gov (United States)

    Beran, Jiri; Van Der Meeren, Olivier; Leyssen, Maarten; D'silva, Priya

    2016-05-23

    The exact duration of antibody persistence to hepatitis A and B and the need for booster dosing following primary immunisation remains undefined. A long-term study was designed to follow antibody persistence and immune memory on an annual basis for up to 15 years following vaccination during adolescence. Subjects received a combined hepatitis A and B vaccine (Twinrix™, GSK Vaccines, Belgium) at 12-15 years of age, either as 2-dose of the adult formulation or 3-dose of the paediatric formulation. Blood samples were taken every year thereafter to assess antibody persistence and immune memory to hepatitis A and B. Antibodies to hepatitis A virus (anti-HAV) and hepatitis B surface antigen (anti-HBs) were measured at Years 11-15. At Year 15 immune memory was further assessed by measuring the anamnestic response to a challenge dose of the monovalent vaccine, which was administered to subjects whose antibody concentrations fell below the pre-defined cut-offs (anti-HAV: hepatitis B vaccine challenge dose administration to 19 subjects, all except one in the 3-dose group, mounted a robust anamnestic response. The safety and reactogenicity profile of the hepatitis B challenge was consistent with previous experience. Immunity to hepatitis A and B persists 15 years after adolescent vaccination with a combined hepatitis A and B vaccine. Highly effective anamnestic response indicates that a booster dose should not be required for 15 years after primary vaccination. http://www.clinicaltrials.govNCT00875485. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Persistent Mullerian duct syndrome in a Miniature Schnauzer dog with signs of feminization and a Sertoli cell tumour.

    Science.gov (United States)

    Vegter, A R; Kooistra, H S; van Sluijs, F J; van Bruggen, L W L; Ijzer, J; Zijlstra, C; Okkens, A C

    2010-06-01

    A 5-year-old male Miniature Schnauzer was presented with unilateral cryptorchidism and signs of feminization. Abdominal ultrasonography revealed an enlarged right testis and a large, fluid-filled cavity that appeared to arise from the prostate. Computed tomography revealed the cavity to be consistent with an enlarged uterine body, arising from the prostate, and showed two structures resembling uterine horns that terminated close to the adjacent testes. The dog had a normal male karyotype, 78 XY. Gonadohysterectomy was performed and both the surgical and the histological findings confirmed the presence of a uterus in this male animal, resulting in a diagnosis of persistent Mullerian duct syndrome (PMDS). The enlarged intra-abdominal testis contained a Sertoli cell tumour. Computed tomography proved to be an excellent diagnostic tool for PMDS.

  13. Modelling the role of Tax expression in HTLV-I persistence in vivo.

    Science.gov (United States)

    Li, Michael Y; Lim, Aaron G

    2011-12-01

    Human T-lymphotropic virus type I (HTLV-I) is a persistent human retrovirus characterized by life-long infection and risk of developing HAM/TSP, a progressive neurological and inflammatory disease, and adult T-cell leukemia (ATL). Chronically infected individuals often harbor high proviral loads despite maintaining a persistently activated immune response. Based on a new hypothesis for the persistence of HTLV-I infection, a three-dimensional compartmental model is constructed that describes the dynamic interactions among latently infected target cells, target-cell activation, and immune responses to HTLV-I, with an emphasis on understanding the role of Tax expression in the persistence of HTLV-I.

  14. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status [Abstract

    Science.gov (United States)

    The circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a H...

  15. Cumulative Antiretroviral Exposure Measured in Hair Is Not Associated With Measures of HIV Persistence or Inflammation Among Individuals on Suppressive ART.

    Science.gov (United States)

    Gandhi, Monica; Gandhi, Rajesh T; Stefanescu, Andrei; Bosch, Ronald J; Cyktor, Joshua C; Horng, Howard; Louie, Alexander; Phung, Nhi; Eron, Joseph J; Hogg, Evelyn; Macatangay, Bernard J C; Hensel, Christopher; Fletcher, Courtney V; Mellors, John W; McMahon, Deborah K

    2018-06-20

    Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation. These findings suggest that higher systemic ARV exposure may not impact HIV persistence or inflammation.

  16. Persistence and changes in bioavailability of dieldrin, DDE and heptachlor epoxide in earthworms over 45 years

    Science.gov (United States)

    Beyer, W. Nelson; Gale, Robert W.

    2013-01-01

    The finding of dieldrin (88 ng/g), DDE (52 ng/g), and heptachlor epoxide (19 ng/g) in earthworms from experimental plots after a single moderate application (9 kg/ha) 45 years earlier attests to the remarkable persistence of these compounds in soil and their continued uptake by soil organisms. Half-lives (with 95 % confidence intervals) in earthworms, estimated from exponential decay equations, were as follows: dieldrin 4.9 (4.3-5.7) years, DDE 5.3 (4.7-6.1) years, and heptachlor epoxide 4.3 (3.8-4.9) years. These half-lives were not significantly different from those estimated after 20 years. Concentration factors (dry weight earthworm tissue/dry weight soil) were initially high and decreased mainly during the first 11 years after application. By the end of the study, average concentration factors were 1.5 (dieldrin), 4.0 (DDE), and 1.8 (heptachlor epoxide), respectively.

  17. Historical data reveal 30-year persistence of benthic fauna associations in heavily modified waterbody

    Directory of Open Access Journals (Sweden)

    Ruth Callaway

    2016-08-01

    Full Text Available Baseline surveys form the cornerstone of coastal impact studies where altered conditions, for example through new infrastructure development, are assessed against a temporal reference state. They are snapshots taken before construction. Due to scarcity of relevant data prior to baseline surveys long-term trends can often not be taken into account. Particularly in heavily modified waterbodies this would however be desirable to control for changes in anthropogenic use over time as well as natural ecological variation. Here, the benthic environment of an industrialized embayment was investigated (Swansea Bay, Wales, UK where it is proposed to build a tidal lagoon that would generate marine renewable energy from the tidal range. Since robust long-term baseline data was not available, the value of unpublished historical benthos information from 1984 by a regional water company was assessed with the aim to improve certainty about the persistence of current benthic community patterns. A survey of 101 positions in 2014 identified spatially discrete benthic communities with areas of high and low diversity. Habitat characteristics including sediment properties and the proximity to a sewage outfall explained 17-35% of the variation in the community structure. Comparing the historical information from 1984 with 2014 revealed striking similarity in the benthic communities between those years, not just in their spatial distribution but also to a large extent in the species composition. The 30-year-old information confirmed spatial boundaries of discrete species associations and pinpointed a similar diversity hotspot. A group of five common species was found to be particularly persistent over time (Nucula nitidosa, Spisula elliptica, Spiophanes bombyx, Nephtys hombergii, Diastylis rathkei. According to the Infauna Quality Index (IQI linked to the EU Water Framework Directive (WFD the average ecological status for 2014 was ‘moderate’, but eleven samples

  18. Persistent Mullerian Duct Syndrome with Transverse Testicular ...

    African Journals Online (AJOL)

    Eastham JA, McEvoy K, Sullivan R, Chandrasoma P. A case of simultaneous bilateral nonseminomatous testicular tumors in persistent müllerian duct syndrome. J Urol 1992;148:407-8. 8. Shinmura Y, Yokoi T, Tsutsui Y. A case of clear cell adenocarcinoma of the müllerian duct in persistent müllerian duct syndrome: The first ...

  19. The Impact of Student Services on First Year Persistence from Emancipated Foster Care Community College Students' Perceptions

    Science.gov (United States)

    Murphy, Ralph Frederick, II

    2016-01-01

    The abysmal persistence to completion rate for at-risk student populations is a concern for higher education leaders; especially, emancipated foster care community college students. Multiple data sources indicate foster care youth are more likely to enroll at community colleges than four-year universities. For this reason, the first-year…

  20. Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires.

    Directory of Open Access Journals (Sweden)

    Mikhail V Pogorelyy

    2017-07-01

    Full Text Available The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which together constitute a "public" repertoire of abundant clonotypes. The TCR repertoire is initially formed prenatally, when the enzyme inserting random nucleotides is downregulated, producing a limited diversity subset. By statistically analyzing deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, we show that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age. Our results suggest that large, low-diversity public clones are created during pre-natal life, and survive over long periods, providing the basis of the public repertoire.

  1. Persistent insomnia is associated with mortality risk.

    Science.gov (United States)

    Parthasarathy, Sairam; Vasquez, Monica M; Halonen, Marilyn; Bootzin, Richard; Quan, Stuart F; Martinez, Fernando D; Guerra, Stefano

    2015-03-01

    Insomnia has been associated with mortality risk, but whether this association is different in subjects with persistent vs intermittent insomnia is unclear. Additionally, the role of systemic inflammation in such an association is unknown. We used data from a community-based cohort to determine whether persistent or intermittent insomnia, defined based on persistence of symptoms over a 6-year period, was associated with death during the following 20 years of follow-up. We also determined whether changes in serum C-reactive protein (CRP) levels measured over 2 decades between study initiation and insomnia determination were different for the persistent, intermittent, and never insomnia groups. The results were adjusted for confounders such as age, sex, body mass index, smoking, physical activity, alcohol, and sedatives. Of the 1409 adult participants, 249 (18%) had intermittent and 128 (9%) had persistent insomnia. During a 20-year follow-up period, 318 participants died (118 due to cardiopulmonary disease). In adjusted Cox proportional-hazards models, participants with persistent insomnia (adjusted hazards ratio [HR] 1.58; 95% confidence interval [CI], 1.02-2.45) but not intermittent insomnia (HR 1.22; 95% CI, 0.86-1.74) were more likely to die than participants without insomnia. Serum CRP levels were higher and increased at a steeper rate in subjects with persistent insomnia as compared with intermittent (P = .04) or never (P = .004) insomnia. Although CRP levels were themselves associated with increased mortality (adjusted HR 1.36; 95% CI, 1.01-1.82; P = .04), adjustment for CRP levels did not notably change the association between persistent insomnia and mortality. In a population-based cohort, persistent, and not intermittent, insomnia was associated with increased risk for all-cause and cardiopulmonary mortality and was associated with a steeper increase in inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Performance Persistence of Equity Funds in Hungary

    Directory of Open Access Journals (Sweden)

    Dariusz Filip

    2011-03-01

    Full Text Available This study examines the phenomenon of performance persistence of equity funds in Hungary in two time perspectives: 1-year and 6-month perspectives. The empirical results confirm the occurrence of performance dependence in consecutive periods. There is also a strong evidence of short-term persistence in the total horizon of the study (from the beginning of 2000 to the end of 2009, and in several sub-periods. The 1-year persistence was also found in the tested sample and, in general, depended on the measure applied. Furthermore, I observed performance reversal, which can be partly explained by trend changes in the financial markets. The persistence of equity funds performance in Hungary is shaped by market factors rather than the diversity of managerial characteristics.

  3. Transcriptional and physiological changes during Mycobacterium tuberculosis reactivation from non-replicating persistence

    Directory of Open Access Journals (Sweden)

    Peicheng Du

    2016-08-01

    Full Text Available Mycobacterium tuberculosis can persist for years in the hostile environment of the host in a non-replicating or slowly replicating state. While active disease predominantly results from reactivation of a latent infection, the molecular mechanisms of M. tuberculosis reactivation are still poorly understood. We characterized the physiology and global transcriptomic profiles of M. tuberculosis during reactivation from hypoxia-induced non-replicating persistence. We found that M. tuberculosis reactivation upon reaeration was associated with a lag phase, in which the recovery of cellular physiological and metabolic functions preceded the resumption of cell replication. Enrichment analysis of the transcriptomic dynamics revealed changes to many metabolic pathways and transcription regulons/subnetworks that orchestrated the metabolic and physiological transformation in preparation for cell division. In particular, we found that M. tuberculosis reaeration lag phase is associated with down-regulation of persistence-associated regulons/subnetworks, including DosR, MprA, SigH, SigE and ClgR, as well as metabolic pathways including those involved in the uptake of lipids and their catabolism. More importantly, we identified a number of up-regulated transcription regulons and metabolic pathways, including those involved in metal transport and remobilization, second messenger-mediated responses, DNA repair and recombination, and synthesis of major cell wall components. We also found that inactivation of the major alternative sigma factors SigE or SigH disrupted exit from persistence, underscoring the importance of the global transcriptional reprogramming during M. tuberculosis reactivation. Our observations suggest that M. tuberculosis lag phase is associated with a global gene expression reprogramming that defines the initiation of a reactivation process.

  4. Persistence of 14C-labeled atrazine and its residues in a field lysimeter soil after 22 years

    International Nuclear Information System (INIS)

    Jablonowski, Nicolai D.; Koeppchen, Stephan; Hofmann, Diana; Schaeffer, Andreas; Burauel, Peter

    2009-01-01

    Twenty-two years after the last application of ring- 14 C-labeled atrazine at customary rate (1.7 kg ha -1 ) on an agriculturally used outdoor lysimeter, atrazine is still detectable by means of accelerated solvent extraction and LC-MS/MS analysis. Extractions of the 0-10 cm soil layer yielded 60% of the residual 14 C-activity. The extracts contained atrazine (1.0 μg kg -1 ) and 2-hydroxy-atrazine (42.5 μg kg -1 ). Extractions of the material of the lowest layer 55-60 cm consisting of fine gravel yielded 93% of residual 14 C-activity, of which 3.4 μg kg -1 was detected as atrazine and 17.7 μg kg -1 was 2-hydroxy-atrazine. The detection of atrazine in the lowest layer was of almost four times higher mass than in the upper soil layer. These findings highlight the fact that atrazine is unexpectedly persistent in soil. The overall persistence of atrazine in the environment might represent a potential risk for successive groundwater contamination by leaching even after 22 years of environmental exposure. - Atrazine and its metabolite 2-hydroxy-atrazine are still present in soil after long-term aging.

  5. Prevalence and Predictors of Persistent Speech Sound Disorder at Eight Years Old: Findings from a Population Cohort Study

    Science.gov (United States)

    Wren, Yvonne; Miller, Laura L.; Peters, Tim J.; Emond, Alan; Roulstone, Sue

    2016-01-01

    Purpose: The purpose of this study was to determine prevalence and predictors of persistent speech sound disorder (SSD) in children aged 8 years after disregarding children presenting solely with common clinical distortions (i.e., residual errors). Method: Data from the Avon Longitudinal Study of Parents and Children (Boyd et al., 2012) were used.…

  6. Decreased Siglec-9 Expression on Natural Killer Cell Subset Associated With Persistent HBV Replication

    Directory of Open Access Journals (Sweden)

    Di Zhao

    2018-05-01

    Full Text Available Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56dim NK cells. Its role in infection diseases has not been investigated yet. Here, we studied the potential regulatory roles of NK Siglec-9 in the pathogenesis of chronic hepatitis B (CHB infection. Flow cytometry evaluated the expression of Siglec-9 and other receptors on peripheral NK cells. Immunofluorescence staining was used to detect Siglec-9 ligands on liver biopsy tissues and cultured hepatocyte cell lines. Siglec-9 blocking assay was carried out and cytokine synthesis and CD107a degranulation was detected by flow cytometry. Compared to healthy donors, CHB patients had decreased Siglec-9+ NK cells, which reversely correlated with serum hepatitis B e antigen and HBV DNA titer. Siglec-9 expression on NK cells from patients achieving sustained virological response recovered to the level of normal donors. Neutralization of Siglec-9 restored cytokine synthesis and degranulation of NK cells from CHB patients. Immunofluorescence staining showed increased expression of Siglec-9 ligands in liver biopsy tissues from CHB patients and in hepatocyte cell lines infected with HBV or stimulated with inflammatory cytokines (IL-6 or TGF-β. These findings identify Siglec-9 as a negative regulator for NK cells contributing to HBV persistence and the intervention of Siglec-9 signaling might be of potentially translational significance.

  7. Evaluation of the persistence of functional and biological respiratory health effects in clean-up workers 6 years after the Prestige oil spill.

    NARCIS (Netherlands)

    Zock, J.P.; Rodríguez-Trigo, G.; Rodríguez-Rodríguez, E.; Souto-Alonso, A.; Espinosa, A.; Pozo-Rodríguez, F.; Gómez, F.P.; Fuster, C.; Castaño-Vinyals, G.; Antó, J.M.; Barberà, J.A.

    2014-01-01

    Fishermen who had participated in clean-up activities of the Prestige oil spill showed increased bronchial responsiveness and higher levels of respiratory biomarkers 2years later. We aimed to evaluate the persistence of these functional and biological respiratory health effects 6years after clean-up

  8. Autoradiographical in-vitro examination of the cell proliferation of persisting psoriatic plaques in preferred areas under therapy with ultraviolet light: Photochemotherapy (PUVA) and selective ultraviolet phototherapy (SUP)

    International Nuclear Information System (INIS)

    Middendorf, M.

    1982-01-01

    The application of ultraviolet rays (PUVA, SUP) brought significant progress in the treatment of psoriasis. The goal of UV-irradiation is to normalise the epidermal growth conditions. The cell cycle of persisting psoriatic plaque in preferred areas was examined under therapy with PUVA and SUP using an autoradiographic in-vitro method, double labelling with 14 C- and 3 H-thymididin. The results were compared to the known cell-kinetic parameters of psoriasis. The values thus obtained confirm the characteristic changes in the cell cycle of psoriasis. Furthermore, there is a block within the DNA-synthesis phase in the plaques persisting under UV-therapy. The resistence of persisting psoriatic plaques in preferred regions against UV-therapy is regarded as an indication of an extreme disturbance in the proliferation behaviour of the psoriatic skin. (orig./MG) [de

  9. Induction and Maintenance of CX3CR1-Intermediate Peripheral Memory CD8+ T Cells by Persistent Viruses and Vaccines

    Directory of Open Access Journals (Sweden)

    Claire Louse Gordon

    2018-04-01

    Full Text Available Summary: The induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8+ T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when memory is sustained at high levels: memory inflation induced by cytomegalovirus (CMV and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T cells showed sustained high levels of CX3R1int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools, in early memory. In humans, CX3CR1int CD8+ T cells were strongly induced following adenovirus-vectored vaccination for hepatitis C virus (HCV (ChAd3-NSmut and during natural CMV infection and were associated with a memory phenotype similar to that in mice. These data indicate that CX3CR1int cells form an important component of the memory pool in response to persistent viruses and vaccines in both mice and humans. : Gordon et al. demonstrate that CX3CR1int peripheral memory T cells are a substantial component of memory inflation induced by persistent CMVs and adenoviral vaccination. They are characterized by sustained proliferation and an effector-memory phenotype linked to these expanded CD8+ T cell memory responses. Core phenotypic features are shared by humans and mice. Keywords: cytomegalovirus, T cells, memory, adenovirus, vaccination, CX3CR1, memory inflation, mouse, human

  10. Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search.

    Directory of Open Access Journals (Sweden)

    G Matthew Fricke

    2016-03-01

    Full Text Available Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Lévy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1 a lognormal distribution of step lengths, 2 motion that is directionally persistent over short time scales, and 3 heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call "hotspots" within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search.

  11. Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search

    Science.gov (United States)

    Fricke, G. Matthew; Letendre, Kenneth A.; Moses, Melanie E.; Cannon, Judy L.

    2016-01-01

    Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Lévy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1) a lognormal distribution of step lengths, 2) motion that is directionally persistent over short time scales, and 3) heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call “hotspots” within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search. PMID:26990103

  12. Biofilm Formation and Disinfectant Susceptibility of Persistent and Nonpersistent Listeria monocytogenes Isolates from Gorgonzola Cheese Processing Plants.

    Science.gov (United States)

    Costa, Annalisa; Bertolotti, Luigi; Brito, Luisa; Civera, Tiziana

    2016-11-01

    The aim of this study was to investigate whether the biofilm-forming ability and/or the disinfectant susceptibility accounted for the persistence of Listeria monocytogenes in Gorgonzola cheese processing plants. For this purpose, a set of 16 L. monocytogenes isolates collected in the 2004-2007 period was analyzed, including 11 persistent isolates collected in different years, within the collection period, and displaying identical or highly correlated pulsotypes. The evaluation of biofilm-forming ability was assessed using crystal violet (CV) staining and the enumeration of viable cells on stainless steel coupons (SSC). Absorbance values obtained with CV staining for persistent and nonpersistent isolates were not significantly different (rm-ANOVA p > 0.05) and the cell counts from nonpersistent isolates showed to be higher compared with persistent isolates (rm-ANOVA p biofilms on SSC, grown in nutrient-rich (dirty) and limiting (clean) conditions using acid acetic-hydrogen peroxide (P3) and acid citric-hydrogen peroxide (MS) commercial disinfectants. The treatment was considered effective when a 4 Log reduction in viable cell count was observed. The Log reductions of persistent and nonpersistent isolates, obtained with both the assays in clean and dirty conditions, were compared and no significant differences were detected (rm-ANOVA p > 0.05). A greater influence of organic matter on MS could explain why P3 was efficient in reducing to effective levels the majority of the isolates at the lowest concentration suggested by the manufacturer (0.2% [v/v]), while the same purpose required a higher concentration (1% [v/v]) of MS. In conclusion, our results demonstrate that the persistence of these isolates in Gorgonzola cheese processing plants was linked neither to the biofilm-forming ability nor to their susceptibility to hydrogen peroxide-based disinfectants; therefore, other factors should contribute to the persistent colonization of the dairies.

  13. Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence.

    Science.gov (United States)

    Heim, Cortney E; Vidlak, Debbie; Odvody, Jessica; Hartman, Curtis W; Garvin, Kevin L; Kielian, Tammy

    2017-11-15

    Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33 + HLA-DR - CD66b + CD14 -/low granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues. MDSCs inhibit T cell proliferation, which coincided with reduced T cells in PJIs compared to aseptic tissues. IL-10, IL-6, and CXCL1 were significantly elevated in PJI tissues and have been implicated in MDSC inhibitory activity, expansion, and recruitment, respectively, which may account for their preferential increase in PJIs. This bias towards G-MDSC accumulation during human PJI could account for the chronicity of these infections by preventing the pro-inflammatory, antimicrobial actions of immune effector cells. Animal models of PJI have revealed a critical role for MDSCs and IL-10 in promoting infection persistence; however, whether this population is prevalent during human PJI and across distinct bacterial pathogens remains unknown. This study has identified that granulocytic-MDSC infiltrates are unique to human PJIs caused by distinct bacteria, which are not associated with aseptic loosening of prosthetic joints. Better defining the immune status of human PJIs could lead to novel immune-mediated approaches to facilitate PJI clearance in combination with conventional antibiotics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  14. Persistent Hyperprolactinemia and Bilateral Galactocele in a Male Infant

    Directory of Open Access Journals (Sweden)

    Casti Tiziana

    2009-02-01

    Full Text Available Galactocele is a benign breast lesion, usually occurring in nursing women. This lesion is a rare cause of breast enlargement in children. In this paper we describe the case of an infant with hyperprolactinemia (which persisted throughout 15 years of clinical observation and bilateral galactocele. We speculate that a congenital midline defect in our patient might have impaired the normal dopaminergic inhibitory tone on pituitary lactotroph cells, thus leading to an increased prolactin secretion by the pituitary gland; this, in turn, might have favored the development of the galactocele.

  15. Immune Evasion Strategies and Persistence of Helicobacter pylori.

    Science.gov (United States)

    Mejías-Luque, Raquel; Gerhard, Markus

    Helicobacter pylori infection is commonly acquired during childhood, can persist lifelong if not treated, and can cause different gastric pathologies, including chronic gastritis, peptic ulcer disease, and eventually gastric cancer. H. pylori has developed a number of strategies in order to cope with the hostile conditions found in the human stomach as well as successful mechanisms to evade the strong innate and adaptive immune responses elicited upon infection. Thus, by manipulating innate immune receptors and related signaling pathways, inducing tolerogenic dendritic cells and inhibiting effector T cell responses, H. pylori ensures low recognition by the host immune system as well as its persistence in the gastric epithelium. Bacterial virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin A, or gamma-glutamyltranspeptidase have been extensively studied in the context of bacterial immune escape and persistence. Further, the bacterium possesses other factors that contribute to immune evasion. In this chapter, we discuss in detail the main evasion and persistence strategies evolved by the bacterium as well as the specific bacterial virulence factors involved.

  16. Early life innate immune signatures of persistent food allergy.

    Science.gov (United States)

    Neeland, Melanie R; Koplin, Jennifer J; Dang, Thanh D; Dharmage, Shyamali C; Tang, Mimi L; Prescott, Susan L; Saffery, Richard; Martino, David J; Allen, Katrina J

    2017-11-14

    Food allergy naturally resolves in a proportion of food-allergic children without intervention; however the underlying mechanisms governing the persistence or resolution of food allergy in childhood are not understood. This study aimed to define the innate immune profiles associated with egg allergy at age 1 year, determine the phenotypic changes that occur with the development of natural tolerance in childhood, and explore the relationship between early life innate immune function and serum vitamin D. This study used longitudinally collected PBMC samples from a population-based cohort of challenge-confirmed egg-allergic infants with either persistent or transient egg allergy outcomes in childhood to phenotype and quantify the functional innate immune response associated with clinical phenotypes of egg allergy. We show that infants with persistent egg allergy exhibit a unique innate immune signature, characterized by increased numbers of circulating monocytes and dendritic cells that produce more inflammatory cytokines both at baseline and following endotoxin exposure when compared with infants with transient egg allergy. Follow-up analysis revealed that this unique innate immune signature continues into childhood in those with persistent egg allergy and that increased serum vitamin D levels correlate with changes in innate immune profiles observed in children who developed natural tolerance to egg. Early life innate immune dysfunction may represent a key immunological driver and predictor of persistent food allergy in childhood. Serum vitamin D may play an immune-modulatory role in the development of natural tolerance. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Intracellular survival of Staphylococcus aureus during persistent infection in the insect Tenebrio molitor.

    Science.gov (United States)

    McGonigle, John E; Purves, Joanne; Rolff, Jens

    2016-06-01

    Survival of bacteria within host cells and tissues presents a challenge to the immune systems of higher organisms. Escape from phagocytic immune cells compounds this issue, as immune cells become potential vehicles for pathogen dissemination. However, the duration of persistence within phagocytes and its contribution to pathogen load has yet to be determined. We investigate the immunological significance of intracellular persistence within the insect model Tenebrio molitor, assessing the extent, duration and location of bacterial recovery during a persistent infection. Relative abundance of Staphylococcus aureus in both intracellular and extracellular fractions was determined over 21 days, and live S. aureus were successfully recovered from both the hemolymph and within phagocytic immune cells across the entire time course. The proportion of bacteria recovered from within phagocytes also increased over time. Our results show that to accurately estimate pathogen load it is vital to account for bacteria persisting within immune cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Lack of CD4+ T cell percent decrease in alemtuzumab-treated multiple sclerosis patients with persistent relapses.

    Science.gov (United States)

    Rolla, Simona; De Mercanti, Stefania Federica; Bardina, Valentina; Horakova, Dana; Habek, Mario; Adamec, Ivan; Cocco, Eleonora; Annovazzi, Pietro; Vladic, Anton; Novelli, Francesco; Durelli, Luca; Clerico, Marinella

    2017-12-15

    Alemtuzumab, a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), induces lymphopenia especially of CD4+ T cells. Here, we report the atypical CD4+ T population behaviour of two patients with persistent disease activity despite repeated alemtuzumab treatments. Whereas lymphocytes count decreased and fluctuated accordingly to alemtuzumab administration, their CD4+ cell percentage was not or just mildly affected and was slightly below the lowest normal limit already before alemtuzumab. These cases anticipate further studies aimed to investigate whether the evaluation of the CD4+ cell percentage could represent a helpful tool to address the individual clinical response to alemtuzumab. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Including persistency of impairment in mild cognitive impairment classification enhances prediction of 5-year decline.

    Science.gov (United States)

    Vandermorris, Susan; Hultsch, David F; Hunter, Michael A; MacDonald, Stuart W S; Strauss, Esther

    2011-02-01

    Although older adults with Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia as a group, heterogeneity of outcomes is common at the individual level. Using data from a prospective 5-year longitudinal investigation of cognitive change in healthy older adults (N = 262, aged 64-92 years), this study addressed limitations in contemporary MCI identification procedures which rely on single occasion assessment ("Single-Assessment [SA] MCI") by evaluating an alternate operational definition of MCI requiring evidence of persistent cognitive impairment over multiple-testing sessions ("Multiple-Assessment [MA] MCI"). As hypothesized, prevalence of SA-MCI exceeded that of MA-MCI. Further, the MA-MCI groups showed lower baseline cognitive and functional performance and steeper cognitive decline compared with Control and SA-MCI group. Results are discussed with reference to retest effects and clinical implications.

  20. Persistence Mechanisms of Conjugative Plasmids

    DEFF Research Database (Denmark)

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting the suc...

  1. Activated ClpP kills persisters and eradicates a chronic biofilm infection.

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian P.; Nakayasu, Ernesto S.; Fleck, Laura E.; LaFleur, Michael D.; Isabella, Vincent M.; Coleman, K.; Leonard, Steve N.; Smith, Richard D.; Adkins, Joshua N.; Lewis, Kim

    2013-11-21

    The current antibiotic crisis stems from two distinct phenomena-drug resistance, and drug tolerance. Resistance mechanisms such as drug efflux or modification prevent antibiotics from binding to their targets 1, allowing pathogens to grow. Antibiotic tolerance is the property of persister cells, phenotypic variants of regular bacteria 2. Antibiotics kill by corrupting targets, but these are inactive in dormant persisters, leading to tolerance. Persisters were first identified by Joseph Bigger in 1944, when he discovered a surviving sub-population of Staphylococcus following treatment with penicillin3. Persisters are largely responsible for recalcitrance of chronic diseases such as tuberculosis, and various infections associated with biofilms - endocarditis, osteomyelitis, infections of catheters and indwelling devices, and deep-seated infections of soft tissues 4. There are a number of redundant pathways involved in persister formation5,6 precluding development of drugs inhibiting their formation. The acyldepsipeptide antibiotic (ADEP 4) has been shown to activate the ClpP protease resulting in death of growing cells 7. Here we show that ADEP4 activated ClpP becomes a fairly non-specific protease and kills persister cells by degradation of over 400 intracellular targets. clpP mutants are resistant to ADEP4 7, but we find that they display increased susceptibility to killing by a range of conventional antibiotics. Combining ADEP4 with rifampicin leads to eradication of persisters, stationary and biofilm populations of Staphylococcus aureus in vitro and in a deep-seated murine infection. Target corruption/activation provides an approach to killing persisters and eradicating chronic infections.

  2. Herbicide Persistence in Seawater Simulation Experiments.

    Directory of Open Access Journals (Sweden)

    Philip Mercurio

    Full Text Available Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR. The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities. Very little degradation was recorded over the standard 60 d period (Experiment 1 so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated

  3. Herbicide Persistence in Seawater Simulation Experiments

    Science.gov (United States)

    Mercurio, Philip; Mueller, Jochen F.; Eaglesham, Geoff; Flores, Florita; Negri, Andrew P.

    2015-01-01

    Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR). The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities). Very little degradation was recorded over the standard 60 d period (Experiment 1) so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated flood plumes

  4. Species Diversity Effects on Productivity, Persistence and Quality of Multispecies Swards in a Four-Year Experiment

    DEFF Research Database (Denmark)

    Jing, Jingying; Søegaard, Karen; Cong, Wen-Feng

    2017-01-01

    ), neutral detergent fiber (NDF) and crude protein (CP), and a lower concentration of ash than the 10-mix and 12-mix. Slurry application increased annual yield production by 10% and changed the botanical composition, increasing the proportion of grass and decreasing the proportion of legumes. Compared......Plant species diversity may benefit natural grassland productivity, but its effect in managed grassland systems is not well understood. A four-year multispecies grassland experiment was conducted to investigate the effect of species diversity±legumes and non-leguminous forbs±on productivity...... increased sward production and yield persistence under cutting regime. The 12-mix had the highest yield from the second year onwards and no statistically significant yield reduction over four years, while annual yields in the 3-mix and 10-mix decreased significantly with increasing grassland age. The higher...

  5. Alterations in adaptive immunity persist during long-duration spaceflight

    Science.gov (United States)

    Crucian, Brian; Stowe, Raymond P; Mehta, Satish; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

    2015-01-01

    Background: It is currently unknown whether immune system alterations persist during long-duration spaceflight. In this study various adaptive immune parameters were assessed in astronauts at three intervals during 6-month spaceflight on board the International Space Station (ISS). AIMS: To assess phenotypic and functional immune system alterations in astronauts participating in 6-month orbital spaceflight. Methods: Blood was collected before, during, and after flight from 23 astronauts participating in 6-month ISS expeditions. In-flight samples were returned to Earth within 48 h of collection for immediate analysis. Assays included peripheral leukocyte distribution, T-cell function, virus-specific immunity, and mitogen-stimulated cytokine production profiles. Results: Redistribution of leukocyte subsets occurred during flight, including an elevated white blood cell (WBC) count and alterations in CD8+ T-cell maturation. A reduction in general T-cell function (both CD4+ and CD8+) persisted for the duration of the 6-month spaceflights, with differential responses between mitogens suggesting an activation threshold shift. The percentage of CD4+ T cells capable of producing IL-2 was depressed after landing. Significant reductions in mitogen-stimulated production of IFNγ, IL-10, IL-5, TNFα, and IL-6 persisted during spaceflight. Following lipopolysaccharide (LPS) stimulation, production of IL-10 was reduced, whereas IL-8 production was increased during flight. Conclusions: The data indicated that immune alterations persist during long-duration spaceflight. This phenomenon, in the absence of appropriate countermeasures, has the potential to increase specific clinical risks for crewmembers during exploration-class deep space missions. PMID:28725716

  6. Postnatal persistent infection with classical Swine Fever virus and its immunological implications.

    Directory of Open Access Journals (Sweden)

    Sara Muñoz-González

    Full Text Available It is well established that trans-placental transmission of classical swine fever virus (CSFV during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs

  7. Phenotypic and genetic heterogeneity within biofilms with particular emphasis on persistence and antimicrobial tolerance.

    Science.gov (United States)

    Sadiq, Faizan A; Flint, Steve; Li, YanJun; Ou, Kai; Yuan, Lei; He, Guo Qing

    2017-09-01

    Phenotypic changes or phase variation within biofilms is an important feature of bacterial dormant life. Enhanced resistance to antimicrobials is one of the distinct features displayed by a fraction of cells within biofilms. It is believed that persisters are mainly responsible for this phenotypic heterogeneity. However, there is still an unresolved debate on the formation of persisters. In this short review, we highlight all known genomic and proteomic changes encountered by bacterial cells within biofilms. We have also described all phenotypic changes displayed by bacterial cells within biofilms with particular emphasis on enhanced antimicrobial tolerance of biofilms with particular reference to persisters. In addition, all currently known models of persistence have been succinctly discussed.

  8. Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage

    International Nuclear Information System (INIS)

    Shen, Yan Nan; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun-Ran; Kim, Su-Hyeon; Hwang, Sang-Gu; Park, Sang Jun; Kim, Chun-Ho; Lee, Kee-Ho

    2014-01-01

    Highlights: •HAS2 may be a promising target for the radiosensitization of human cancer. •HAS2 is elevated (up to ∼10-fold) in irradiated radioresistant and -sensitive cancer cells. •HAS2 knockdown sensitizes cancer cells to radiation. •HAS2 knockdown potentiates irradiation-induced DNA damage and apoptotic death. •Thus, the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. -- Abstract: Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates various aspects of cancer progression, including migration, invasion and angiogenesis. However, the possible association of HAS2 with the response of cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis in cancer cells. Upon exposure to radiation, all of the tested human cancer cell lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24 h. Inhibition of HAS2 induction significantly reduced the survival of irradiated radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the cells to sustain irradiation-induced DNA damage, thereby leading to an increase of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage, further suggesting that the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. Thus, HAS2 could potentially be targeted for therapeutic interventions aimed at radiosensitizing cancer cells

  9. Persistence of the effect of the Lung Health Study (LHS) smoking intervention over eleven years.

    Science.gov (United States)

    Murray, Robert P; Connett, John E; Rand, Cynthia S; Pan, Wei; Anthonisen, Nicholas R

    2002-10-01

    Research on the long-term persistence of effects of interventions aimed at smoking cessation is limited. This paper examined the quitting behavior of individuals who were randomized to a smoking cessation intervention (SI) or to usual care (UC), at a point approximately 11 years later. The initial sample consisted of 5,887 adult smokers in 10 clinics who had evidence of airways obstruction. Two-thirds of the original participants were offered an intensive 12-week smoking cessation intervention. Of these, 4,517 were enrolled in the long-term follow-up study. Randomized group assignment was a strong predictor of smoking behavior after 11 years, in that 21.9% of SI participants and only 6.0% of UC participants maintained abstinence throughout the interval. Logistic regressions identified covariates associated with abstinence. A higher proportion of abstinence was observed in participants that had been assigned to SI (OR = 4.45), were older (OR = 1.11, increment 5 years), had more years of education (OR = 1.05), and fewer cigarettes/day at baseline (OR = 0.90, increment 10 cigarettes). Smokers exposed to an aggressive smoking intervention program and who sustain abstinence for a five-year period are very likely to still be abstinent after 11 years. Copyright 2002 American Health Foundation and Elsevier Science (USA)

  10. Symptom reduction in young people (15 – 30 years) after a brief behavioral intervention for persistent post-concussion symptoms: An uncontrolled study

    DEFF Research Database (Denmark)

    Thastum, Mille; Rask, Charlotte Ulrikka; Næss-Schmidt, Erhard

    2017-01-01

    on principles from cognitive-behavioral therapy and gradual return to activities. The primary treatment objective was to reduce PCS and prevent chronification of symptoms by reducing negative illness perceptions (eg. beliefs that one cannot control the symptoms and that they will persist), and reducing......Background: About 5 – 15 % of patients with concussion experience persistent post-concussion symptoms (PCS) longer than 3 months post-injury. Currently, treatment options are limited, and no evidence-based intervention is available. Recent studies suggest that cognitive and behavioral processes may...... be involved in symptom maintenance. Aim: To explore in an uncontrolled study design: 1) the overall outcome of a newly developed, brief behavioral intervention in young patients (15 – 30 years) with persistent PCS 3 – 6 months after concussion, and 2) the hypothesised mediators, i.e. illness perceptions...

  11. Photocarcinogenesis and persistent hyperplasia in UV-irradiated SENCAR mouse skin

    International Nuclear Information System (INIS)

    Strickland, P.T.

    1986-01-01

    Susceptibility to photocarcinogenesis has been examined in several mouse strains and stocks including SENCAR, CD-1, BALB/c, C3H, C57Bl, and NZB. SENCAR mice are hypersusceptible to tumorigenesis caused by single high dose exposures to ultraviolet (UV) radiation but not by chronic low-dose exposures. SENCAR mice also exhibit an exaggerated and persistent epidermal hyperplasia in response to UV-induced tissue damage. The persistent hyperplasia is apparently due to a sustained proliferation of the epithelial basal cells, rather than to delayed cell differentiation. SENCAR mice did not exhibit persistent hyperplasia following other forms of tissue damage (surgical or thermal). In related studies, the levels of thymine dimers induced in SENCAR epidermis by UV radiation were comparable to those observed in BALB/c epidermis. In addition, no differences were found in the tissue distribution or persistence of thymine dimers in SENCAR and BALB/c skin

  12. Persistent viral infections and immune aging.

    Science.gov (United States)

    Brunner, Stefan; Herndler-Brandstetter, Dietmar; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

    2011-07-01

    Immunosenescence comprises a set of dynamic changes occurring to both, the innate as well as the adaptive immune system that accompany human aging and result in complex manifestations of still poorly defined deficiencies in the elderly population. One of the most prominent alterations during aging is the continuous involution of the thymus gland which is almost complete by the age of 50. Consequently, the output of naïve T cells is greatly diminished in elderly individuals which puts pressure on homeostatic forces to maintain a steady T cell pool for most of adulthood. In a great proportion of the human population, this fragile balance is challenged by persistent viral infections, especially Cytomegalovirus (CMV), that oblige certain T cell clones to monoclonally expand repeatedly over a lifetime which then occupy space within the T cell pool. Eventually, these inflated memory T cell clones become exhausted and their extensive accumulation accelerates the age-dependent decline of the diversity of the T cell pool. As a consequence, infectious diseases are more frequent and severe in elderly persons and immunological protection following vaccination is reduced. This review therefore aims to shed light on how various types of persistent viral infections, especially CMV, influence the aging of the immune system and highlight potential measures to prevent the age-related decline in immune function. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Missed diagnosis-persistent delirium

    Directory of Open Access Journals (Sweden)

    Aseem Mehra

    2014-01-01

    Full Text Available Delirium is in general considered as an acute short lasting reversible neuropsychiatric syndrome. However, there is some evidence to suggest that in a small proportion of cases delirium may be a chronic or persistent condition. However, making this diagnosis requires clinical suspicion and ruling other differential diagnosis. In this report, we present a case of a 55-year-old man who had cognitive symptoms, psychotic symptoms and depressive symptoms along with persistent hypokalemia and glucose intolerance. He was seen by 3 psychiatrists with these symptoms and was initially diagnosed as having depressive disorder and later diagnosis of bipolar affective disorder (current episode mania, and psychosis were considered by the third psychiatrist. However, despite the presence of persistent neurocognitive deficits, evening worsening of symptoms, hypokalemia and glucose intolerance diagnosis of delirium was not suspected.

  14. Mutant human FUS Is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells.

    Directory of Open Access Journals (Sweden)

    Jamie Rae Acosta

    Full Text Available FUS mutations can occur in familial amyotrophic lateral sclerosis (fALS, a neurodegenerative disease with cytoplasmic FUS inclusion bodies in motor neurons. To investigate FUS pathology, we generated transgenic zebrafish expressing GFP-tagged wild-type or fALS (R521C human FUS. Cell cultures were made from these zebrafish and the subcellular localization of human FUS and the generation of stress granule (SG inclusions examined in different cell types, including differentiated motor neurons. We demonstrate that mutant FUS is mislocalized from the nucleus to the cytosol to a similar extent in motor neurons and all other cell types. Both wild-type and R521C FUS localized to SGs in zebrafish cells, demonstrating an intrinsic ability of human FUS to accumulate in SGs irrespective of the presence of disease-associated mutations or specific cell type. However, elevation in relative cytosolic to nuclear FUS by the R521C mutation led to a significant increase in SG assembly and persistence within a sub population of vulnerable cells, although these cells were not selectively motor neurons.

  15. Quantitative analysis of the acute and long-term CD4(+) T-cell response to a persistent gammaherpesvirus

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to B lymphocytes. The virus-specific CD4(+) T-cell response in C57BL/6 mice challenged intranasally with MHV-68 is detected first...... in the mediastinal lymph nodes and then in the cervical lymph nodes and the spleen. The numbers of MHV-68-specific CD4(+) T cells generated in congenic mice homozygous for disruption of the beta2-microglobulin gene tended to be higher, indicating that the absence of the CD8(+) set in this group resulted...... in a compensatory response. The peak frequency within the splenic CD4(+) T-cell population may reach 1:50 in the acute response; it then drops to 1:400 to 1:500 within 4 months and stays at that level in the very long term. Sorting for L-selectin (CD62L) expression established that all virus-specific CD4(+) T cells...

  16. Thoracoscopic pericardial fenestration for persistent pericardial effusion after radiotherapy for esophageal cancer. Report of a case

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Kazuhiro; Tsuchida, Kazuhito; Ariga, Takamitsu [Yokohama Rosai Hospital (Japan)

    2002-11-01

    We performed thoracoscopic pericardial fenestration for persistent pericardial effusion after radiotherapy for esophageal cancer. An 85-year-old man who had radiation therapy (70.2 Gy) for esophageal cancer was admitted for shortness of breath. Chest computed tomography showed a pericardial effusion. During the 6 months prior to this admission, the patient had undergone percutaneous pericardial drainage 3 times for cardiac tamponade. We performed thoracoscopic partial pericardiectomy with creation of a pleuropericardial window via one access port. Histopathologically, no malignant cells were found in either the resected pericardium or the pericardial effusion. Therefore, we believe the persistent pericardial effusion was secondary to radiotherapy. There was no recurrence of the pericardial effusion for 7 months postoperatively. In summary, thoracoscopic pericardial fenestration is useful in both the diagnosis and treatment of persistent pericardial effusion. (author)

  17. Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway.

    Science.gov (United States)

    Fineran, Paul; Lloyd-Evans, Emyr; Lack, Nathan A; Platt, Nick; Davis, Lianne C; Morgan, Anthony J; Höglinger, Doris; Tatituri, Raju Venkata V; Clark, Simon; Williams, Ian M; Tynan, Patricia; Al Eisa, Nada; Nazarova, Evgeniya; Williams, Ann; Galione, Antony; Ory, Daniel S; Besra, Gurdyal S; Russell, David G; Brenner, Michael B; Sim, Edith; Platt, Frances M

    2016-11-18

    Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis , achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed. Macrophages infected with persistent intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca 2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that persistent intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca 2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria

  18. Cigarette Smoke-Induced Cell Death Causes Persistent Olfactory Dysfunction in Aged Mice

    Directory of Open Access Journals (Sweden)

    Rumi Ueha

    2018-06-01

    Full Text Available Introduction: Exposure to cigarette smoke is a cause of olfactory dysfunction. We previously reported that in young mice, cigarette smoke damaged olfactory progenitors and decreased mature olfactory receptor neurons (ORNs, then, mature ORNs gradually recovered after smoking cessation. However, in aged populations, the target cells in ORNs by cigarette smoke, the underlying molecular mechanisms by which cigarette smoke impairs the regenerative ORNs, and the degree of ORN regeneration after smoking cessation remain unclear.Objectives: To explore the effects of cigarette smoke on the ORN cell system using an aged mouse model of smoking, and to investigate the extent to which smoke-induced damage to ORNs recovers following cessation of exposure to cigarette smoke in aged mice.Methods: We intranasally administered a cigarette smoke solution (CSS to 16-month-old male mice over 24 days, then examined ORN existence, cell survival, changes of inflammatory cytokines in the olfactory epithelium (OE, and olfaction using histological analyses, gene analyses and olfactory habituation/dishabituation tests.Results: CSS administration reduced the number of mature ORNs in the OE and induced olfactory dysfunction. These changes coincided with an increase in the number of apoptotic cells and Tumor necrosis factor (TNF expression and a decrease in Il6 expression. Notably, the reduction in mature ORNs did not recover even on day 28 after cessation of treatment with CSS, resulting in persistent olfactory dysfunction.Conclusion: In aged mice, by increasing ORN death, CSS exposure could eventually overwhelm the regenerative capacity of the OE, resulting in continued reduction in the number of mature ORNs and olfactory dysfunction.

  19. Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of Justice, Shanghai 200063 (China); Liu, Siwen [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Bode, Liv [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Liu, Chengyu [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Zhang, Liang [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Wang, Xiao [Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016 (China); Li, Dan [Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing 400016 (China); Lei, Yang [Department of Internal Medicine, University-Town Hospital of Chongqing Medical University, Chongqing 400016 (China); Peng, Xiaojun [Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou 310018 (China); Cheng, Zhongyi [Advanced Institute of Translational Medicine, Tongji University, Shanghai 200092 (China); and others

    2015-11-15

    Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

  20. Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

    International Nuclear Information System (INIS)

    Liu, Xia; Liu, Siwen; Bode, Liv; Liu, Chengyu; Zhang, Liang; Wang, Xiao; Li, Dan; Lei, Yang; Peng, Xiaojun; Cheng, Zhongyi

    2015-01-01

    Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

  1. Impact of persistence and non-persistence in leisure time physical activity on coronary heart disease and all-cause mortality

    DEFF Research Database (Denmark)

    Schnohr, Peter; O'Keefe, James H.; Lange, Peter

    2017-01-01

    Aims: The aim of this study was to investigate the impact of persistence and non-persistence in leisure time physical activity on coronary heart disease and all-cause mortality. Methods and results: In the Copenhagen City Heart Study, we prospectively followed 12,314 healthy subjects for 33 years...

  2. PDZ binding motif of HTLV-1 Tax promotes virus-mediated T-cell proliferation in vitro and persistence in vivo.

    Science.gov (United States)

    Xie, Li; Yamamoto, Brenda; Haoudi, Abdelali; Semmes, O John; Green, Patrick L

    2006-03-01

    HTLV-1 cellular transformation and disease induction is dependent on expression of the viral Tax oncoprotein. PDZ is a modular protein interaction domain used in organizing signaling complexes in eukaryotic cells through recognition of a specific binding motif in partner proteins. Tax-1, but not Tax-2, contains a PDZ-binding domain motif (PBM) that promotes the interaction with several cellular PDZ proteins. Herein, we investigate the contribution of the Tax-1 PBM in HTLV-induced proliferation and immortalization of primary T cells in vitro and viral survival in an infectious rabbit animal model. We generated several HTLV-1 and HTLV-2 Tax viral mutants, including HTLV-1deltaPBM, HTLV-2+C22(+PBM), and HTLV-2+ C18(deltaPBM). All Tax mutants maintained the ability to significantly activate the CREB/ATF or NFkappaB signaling pathways. Microtiter proliferation assays revealed that the Tax-1 PBM significantly increases both HTLV-1- and HTLV-2-induced primary T-cell proliferation. In addition, Tax-1 PBM was responsible for the micronuclei induction activity of Tax-1 relative to that of Tax-2. Viral infection and persistence were severely attenuated in rabbits inoculated with HTLV-1deltaPBM. Our results provide the first direct evidence suggesting that PBM-mediated associations between Tax-1 and cellular proteins play a key role in HTLV-induced cell proliferation and genetic instability in vitro and facilitate viral persistence in vivo.

  3. Search along persistent random walks

    International Nuclear Information System (INIS)

    Friedrich, Benjamin M

    2008-01-01

    Optimal search strategies and their implementations in biological systems are a subject of active research. Here we study a search problem which is motivated by the hunt of sperm cells for the egg. We ask for the probability for an active swimmer to find a target under the condition that the swimmer starts at a certain distance from the target. We find that success probability is maximal for a certain level of fluctuations characterized by the persistence length of the swimming path of the swimmer. We derive a scaling law for the optimal persistence length as a function of the initial target distance and search time by mapping the search on a polymer physics problem

  4. Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous T-cell lymphoma

    International Nuclear Information System (INIS)

    Lansigan, Frederick; Stearns, Diane M; Foss, Francine

    2010-01-01

    Denileukin diftitox (Ontak ® ) is indicated for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL), a rare lymphoproliferative disorder of the skin. Denileukin diftitox was the first fusion protein toxin approved for the treatment of a human disease. This fusion protein toxin combines the IL2 protein with diphtheria toxin, and targets the CD25 subunit of the IL2 receptor, resulting in the unique delivery of a cytocidal agent to CD-25 bearing T-cells. Historically, immunotherapy targeting malignant T-cells including monoclonal antibodies has been largely ineffective as cytocidal agents compared to immunotherapy directed against B-cells such as rituximab. This review will summarize the development of denileukin diftitox, its proposed mechanism of action, the pivotal clinical trials that led to its FDA approval, the improvements in quality of life, and the common toxicities experienced during the treatment of patients with CTCL. CTCL is often a chronic progressive lymphoma requiring the sequential use of treatments such as retinoids, traditional chemotherapy, or biological response modifiers. The incorporation of the immunotoxin denileukin diftitox into the sequential or combinatorial treatment of CTCL will also be addressed

  5. Sundials in the shade: A study of women's persistence in the first year of a computer science program in a selective university

    Science.gov (United States)

    Powell, Rita Manco

    Currently women are underrepresented in departments of computer science, making up approximately 18% of the undergraduate enrollment in selective universities. Most attrition in computer science occurs early in this major, in the freshman and sophomore years, and women drop out in disproportionately greater numbers than their male counterparts. Taking an ethnographic approach to investigating women's experiences and progress in the first year courses in the computer science major at the University of Pennsylvania, this study examined the pre-college influences that led these women to the major and the nature of their experiences in and outside of class with faculty, peers, and academic support services. This study sought an understanding of the challenges these women faced in the first year of the major with the goal of informing institutional practice about how to best support their persistence. The research reviewed for this study included patterns of leaving majors in science, math and engineering (Seymour & Hewitt 1997), the high school preparation needed to pursue math and engineering majors in college (Strenta, Elliott, Adair, Matier, & Scott, 1994), and intervention programs that have positively impacted persistence of women in computer science (Margolis & Fisher, 2002). The research method of this study employed a series of personal interviews over the course of one calendar year with fourteen first year women who had either declared on intended to declare the computer science major in the School of Engineering and Applied Science at the University of Pennsylvania. Other data sources were focus groups and personal interviews with faculty, administrators, admissions and student life professionals, teaching assistants, female graduate students, and male first year students at the University of Pennsylvania. This study found that the women in this study group came to the University of Pennsylvania with a thorough grounding in mathematics, but many either had

  6. Students' Persistence and Academic Success in a First-Year Professional Bachelor Program: The Influence of Students' Learning Strategies and Academic Motivation

    OpenAIRE

    Vanthournout, Gert; Gijbels, David; Coertjens, Liesje; Donche, Vincent; Van Petegem, Peter

    2012-01-01

    The present study explores whether students' learning strategies and academic motivation predict persistence and academic success in the first year of higher education. Freshmen students in a professional bachelor program in teacher education were questioned on their learning strategy use and motivation at the start and at the end of the academic year. Students' learning strategies were assessed using the inventory of learning styles-SV. Motivation was measured using scales from the self-regu...

  7. Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Florian M. Corvinus

    2005-06-01

    Full Text Available Colorectal carcinoma (CRC is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.

  8. Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus.

    Directory of Open Access Journals (Sweden)

    Taisheng Li

    2006-12-01

    Full Text Available Most of the individuals infected with SARS coronavirus (SARS-CoV spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

  9. Polarized and persistent Ca²⁺ plumes define loci for formation of wall ingrowth papillae in transfer cells.

    Science.gov (United States)

    Zhang, Hui-Ming; Imtiaz, Mohammad S; Laver, Derek R; McCurdy, David W; Offler, Christina E; van Helden, Dirk F; Patrick, John W

    2015-03-01

    Transfer cell morphology is characterized by a polarized ingrowth wall comprising a uniform wall upon which wall ingrowth papillae develop at right angles into the cytoplasm. The hypothesis that positional information directing construction of wall ingrowth papillae is mediated by Ca(2+) signals generated by spatiotemporal alterations in cytosolic Ca(2+) ([Ca(2+)]cyt) of cells trans-differentiating to a transfer cell morphology was tested. This hypothesis was examined using Vicia faba cotyledons. On transferring cotyledons to culture, their adaxial epidermal cells synchronously trans-differentiate to epidermal transfer cells. A polarized and persistent Ca(2+) signal, generated during epidermal cell trans-differentiation, was found to co-localize with the site of ingrowth wall formation. Dampening Ca(2+) signal intensity, by withdrawing extracellular Ca(2+) or blocking Ca(2+) channel activity, inhibited formation of wall ingrowth papillae. Maintenance of Ca(2+) signal polarity and persistence depended upon a rapid turnover (minutes) of cytosolic Ca(2+) by co-operative functioning of plasma membrane Ca(2+)-permeable channels and Ca(2+)-ATPases. Viewed paradermally, and proximal to the cytosol-plasma membrane interface, the Ca(2+) signal was organized into discrete patches that aligned spatially with clusters of Ca(2+)-permeable channels. Mathematical modelling demonstrated that these patches of cytosolic Ca(2+) were consistent with inward-directed plumes of elevated [Ca(2+)]cyt. Plume formation depended upon an alternating distribution of Ca(2+)-permeable channels and Ca(2+)-ATPase clusters. On further inward diffusion, the Ca(2+) plumes coalesced into a uniform Ca(2+) signal. Blocking or dispersing the Ca(2+) plumes inhibited deposition of wall ingrowth papillae, while uniform wall formation remained unaltered. A working model envisages that cytosolic Ca(2+) plumes define the loci at which wall ingrowth papillae are deposited. © The Author 2014. Published by Oxford

  10. Prenatal exposure to persistent organochlorine pollutants is associated with high insulin levels in 5-year-old girls

    DEFF Research Database (Denmark)

    Tang-Péronard, Jeanett L.; Heitmann, Berit L.; Jensen, Tina K.

    2015-01-01

    ® technology. Insulin and leptin concentrations were transformed from continuous to binary variables, using the 75th percentile as a cut-off point. Multiple logistic regression was used to investigate associations between prenatal POP exposures and non-fasting serum concentrations of insulin and leptin at age......BACKGROUND: Several persistent organochlorine pollutants (POPs) possess endocrine disrupting abilities, thereby potentially leading to an increased risk of obesity and metabolic diseases, especially if the exposure occurs during prenatal life. We have previously found associations between prenatal......-year-old children, thus possibly mediating the association with overweight and obesity at 7 years of age. METHODS: The analyses were based on a prospective Faroese Birth Cohort (n=656), recruited between 1997 and 2000. Major POPs, polychlorinated biphenyls (PCBs), p...

  11. No Exit: Predicting Student Persistence. AIR 1990 Annual Forum Paper.

    Science.gov (United States)

    Beil, Cheryl; Shope, Janet H.

    A longitudinal study was conducted to determine the factors influencing college student persistence in remaining in school. Persistence was examined at two points: after the first year and 4 years after enrollment. The study was conducted at an urban university using the American College Testing's Entering Student Survey and Student Opinion…

  12. Evolution of the persistence of snow over Sierra Nevada Mountain (southern, Spain) in the last 55 years

    Science.gov (United States)

    Pimentel, Rafael; José Pérez-Palazón, María; Herrero, Javier; José Polo, María

    2016-04-01

    Snow plays a crucial role in mountainous areas, not only as water resources for human supply, irrigation and energy production, but also for the ecosystem, flora and fauna, over these areas. Sierra Nevada Mountains, southern Spain, constitutes a rich reservoir of endemic wildlife species, and it is considered the most important center of biodiversity in the wester Mediterranean region. The highest regions of the range were declared UNESCO Biosphere Reserve, Natural and National Parks. Climate trends over the last decades put a lot of pressure on both snowfall occurrence and snow persistence; this poses a risk for biodiversity and has led to its inclusion in the Global Change Observatory Network. This work quantifies the evolution of the persistence of snow over the Sierra Nevada area during the last fifty-five years (1960-2015) as a basis to assess the vulnerability of its ecosystem services. For this, the spatial distribution of the annual number of days with snow, SDS, was analyzed over a study area of 4583 km2 (140-3479 m.a.s.l.), which comprises the head of the five basins in these mountains. The following indicator variables were studied over the whole area and each one of the five head regions identified: 1) the trend of SDS; 2) the annual area where SDS exceeded selected percentiles in its distribution; and 3) the annual minimum altitude where SDS exceeded those percentiles. SDS was obtained during the study period by means of the snow module in WiMMed (Watershed Integrated Model in Mediterranean Environment), a physically-based hydrological model developed, calibrated and validated in the area; the model is based on an energy-mass balance over the snowpack that is spatially distributed through the use of depletion curves, and is operational at hourly and daily scales. A general decreasing trend of SDS (0.25 days year-1) was found over the whole study area for the study period. This value is higher in the more humid basins (0.45 and 0.41 days year-1) than in

  13. Persistent and recurrent hyperparathyroidism.

    Science.gov (United States)

    Guerin, Carole; Paladino, Nunzia Cinzia; Lowery, Aoife; Castinetti, Fréderic; Taieb, David; Sebag, Fréderic

    2017-06-01

    Despite remarkable progress in imaging modalities and surgical management, persistence or recurrence of primary hyperparathyroidism (PHPT) still occurs in 2.5-5% of cases of PHPT. The aim of this review is to expose the management of persistent and recurrent hyperparathyroidism. A literature search was performed on MEDLINE using the search terms "recurrent" or "persistent" and "hyperparathyroidism" within the past 10 years. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Before considering reoperation, the surgeon must confirm the diagnosis of PHPT. Then, the patient must be evaluated with new imaging modalities. A single adenoma is found in 68% of cases, multiglandular disease in 28%, and parathyroid carcinoma in 3%. Others causes (<1%) include parathyromatosis and graft recurrence. The surgeon must balance the benefits against the risks of a reoperation (permanent hypocalcemia and recurrent laryngeal nerve palsy). If surgery is necessary, a focused approach can be considered in cases of significant imaging foci, but in the case of multiglandular disease, a bilateral neck exploration could be necessary. Patients with multiple endocrine neoplasia syndromes are at high risk of recurrence and should be managed regarding their hereditary pathology. The cure rate of persistent-PHPT or recurrent-PHPT in expert centers is estimated from 93 to 97%. After confirming the diagnosis of PHPT, patients with persistent-PHPT and recurrent-PHPT should be managed in an expert center with all dedicated competencies.

  14. Clinical isolates of GB virus type C vary in their ability to persist and replicate in peripheral blood mononuclear cell cultures

    International Nuclear Information System (INIS)

    George, Sarah L.; Xiang Jinhua; Stapleton, Jack T.

    2003-01-01

    GB virus C/hepatitis G virus (GBV-C) replication in vitro is inefficient and inconsistent. In this study, clinical isolates of GBV-C were evaluated using peripheral blood mononuclear cell (PBMC) based culture methods. Isolates varied consistently in their ability to persistently replicate, and yield increased in cells grown without PHA/IL-2 stimulation. The deduced polyprotein sequence of an isolate that replicated well was determined (GenBank AY196904) and compared to 20 full-length GBV-C sequences. Fourteen of the 16 unique amino acid polymorphisms identified were in the coding regions for nonstructural proteins associated with interferon resistance and RNA replication. These data indicate that clinical GBV-C isolates vary in their ability to persist in culture, do not require PHA/IL-2 stimulation, and that sequence variability in key regulatory regions may affect growth in PBMC cultures. Since GBV-C appears to inhibit HIV replication in a coinfection model, these studies should facilitate determination of the mechanism of this interaction

  15. Predictors of Persistent Anaemia in the First Year of Antiretroviral Therapy: A Retrospective Cohort Study from Goma, the Democratic Republic of Congo.

    Directory of Open Access Journals (Sweden)

    Pierre Zalagile Akilimali

    Full Text Available Anaemia is associated with adverse outcomes including early death in the first year of antiretroviral therapy (ART. This study reports on the factors associated with persistent anaemia among HIV-infected patients initiating ART in the Democratic Republic of Congo (DR Congo.We conducted a retrospective cohort study and analyzed data from patients receiving HIV care between January 2004 and December 2012 at two major hospitals in Goma, DR Congo. Haemoglobin concentrations of all patients on ART regimen were obtained prior to and within one year of ART initiation. A logistic regression model was used to identify the predictors of persistent anaemia after 12 months of ART.Of 756 patients, 69% of patients were anaemic (IC95%: 65.7-72.3 at baseline. After 12 months of follow up, there was a 1.2 g/dl average increase of haemoglobin concentration (P < 0.001 with differences depending on the therapeutic regimen. Patients who received zidovudine (AZT gained less than those who did not receive AZT (0.99 g/dl vs 1.33 g/dl; p< 0.001. Among 445 patient who had anaemia at the beginning, 33% (147/445 had the condition resolved. Among patients with anaemia at ART initiation, those who did not receive cotrimoxazole prophylaxis before starting ART(AOR 3.89; 95% CI 2.09-7.25; P < 0.001 and a AZT initial regimen (AOR 2.19; 95% CI 1.36-3.52; P < 0.001 were significantly at risk of persistent anaemia.More than two thirds of patients had anaemia at baseline. The AZT-containing regimen and absence of cotrimoxazole prophylaxis before starting ART were associated with persistent anaemia 12 months, after initiation of treatment. Considering the large proportion of patients with persistence of anaemia at 12 months, we suggest that it is necessary to conduct a large study to assess anaemia among HIV-infected patients in Goma.

  16. Induction and persistence of chromosome aberrations in human lymphocytes exposed to neutrons in vitro or in vivo: Implications of findings in 'retrospective' biological dosimetry

    International Nuclear Information System (INIS)

    Littlefield, L.G.; McFee, A.F.; Sayer, A.M.; O'Neill, J.P.; Kleinerman, R.A.; Maor, M.H.

    2000-01-01

    The induction and persistence were evaluated of chromosome aberrations in lymphocytes exposed in vitro to highly efficient 1 MeV monoenergetic neutrons and in patients who received fast neutrons as therapy for tumours. For the in vitro studies, lymphocytes were exposed to various doses of neutrons and cultured for one or 20 cell cycles. Aberrations were quantified in painted chromosome pairs 1, 2 or 4. These 1 MeV neutrons were highly efficient in inducing aberrations, and dicentrics as well as one-way and two-way translocations increased as a linear function of dose. About 30% of the aberrant metaphases displayed complex aberrations. After multiple in vitro cell divisions, virtually all asymmetrical aberrations had been eliminated from the cell population, and the frequency of one-way translocations was reduced dramatically. In contrast, most two-way translocations apparently survived through multiple cell divisions and still displayed excellent correlation with dose after 20 cell cycles. Classical methods were used to evaluate persistence of aberrations in patients who received fractionated neutron therapy to tumours located in many different sites. Neutron induced dicentrics and rings disappeared from the peripheral circulation within the first three years after exposure, while translocations persisted for more than 17 y. However, considerable variability in numbers of aberrations were observed between patients who had received similar 'average bone marrow doses'. Results of these studies are discussed in relation to the possible use of translocations as retrospective dosemeters in persons exposed to radiation many years ago. (author)

  17. Persistence of foot-and mouth disease virus in ruminants

    DEFF Research Database (Denmark)

    Stenfeldt, Carolina; Belsham, Graham; Tjørnehøj, Kirsten

    squamous epithelia of the coronary bands and oral cavity within a few days of infection. Viremia occurs within 2-3 days of infection, but is rapidly cleared through the effect of circulating antibodies of the adaptive immune response. The host response involves initial activation of the innate immune...... response, with activation and recruitment of effector-cells, and subsequent activation of T- and B-cells, leading to the production of circulating antibodies, as well as activation of cytotoxic T-cells. In ruminants, approximately 50% of animals infected with FMDV develop into persistently infected carrier...... animals, with intermittent excretion of live virus, whilst remaining animals clear the infection effectively. Previous experiments have indicated that the site of persistent viral replication is located in pharyngeal lymphoid tissue, as well as the basal epithelia of the dorsal soft palate...

  18. Do gender disparities persist in gastroenterology after 10 years of practice?

    Science.gov (United States)

    Singh, Aparajita; Burke, Carol A; Larive, Brett; Sastri, Suriya V

    2008-07-01

    Cross-sectional studies confirm gender disparity in many aspects of the practice of medicine and surgery. Some data suggest the disparities diminish after 10 yr of practice. This study aims to examine gender discrepancies in income, social, and professional status of gastroenterologists after 10 yr of practice. Prospective, observational, cohort study of gastroenterologists incepted upon graduation from a U.S. GI fellowship program in 1993 and 1995. A 36-item questionnaire was sent to the cohort at 3, 5, and 10 yr after graduation from GI fellowship training. The following are the results of the final, 10th year survey. A total of 168 men and 25 women (mean age 45.5 yr) responded. Men and women were equally likely to be board certified and married, however, women had fewer children. Men earned a mean annual gross income of $375,000 versus$245,000 for women (P= 0.001). After adjusting for practice setting, work hours, practice-ownership, free endoscopy center practice, and vacation time, female gastroenterologists earned $82,000 (22%) less per year than their male colleagues (95% CI $34,000-130,000, P= 0.001). Women were more frequently in academic practice (38%vs 17%), but were less likely to hold the most advanced academic positions. After 10 yr of practice, significant economic, professional, and social disparities persist between male and female gastroenterologists in this cohort. Women were more likely to practice in a setting with flexible work hours, a family leave provision, and in a practice with other women. Initiatives to equalize pay and ensure opportunities for professional advancement for women may diminish the significant practice disparities incurred by women in gastroenterology.

  19. Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence.

    Science.gov (United States)

    Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Charleston, Bryan; Juleff, Nicholas

    2016-05-15

    Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more

  20. Reduced Inferior and Orbital Frontal Thickness in Adolescent Bulimia Nervosa Persists Over Two-Year Follow-Up.

    Science.gov (United States)

    Cyr, Marilyn; Kopala-Sibley, Daniel C; Lee, Seonjoo; Chen, Chen; Stefan, Mihaela; Fontaine, Martine; Terranova, Kate; Berner, Laura A; Marsh, Rachel

    2017-10-01

    Cross-sectional data suggest functional and anatomical disturbances in inferior and orbital frontal regions in bulimia nervosa (BN). Using longitudinal data, we investigated whether reduced cortical thickness (CT) in these regions arises early and persists over adolescence in BN, independent of symptom remission, and whether CT reductions are markers of BN symptoms. A total of 33 adolescent females with BN symptoms (BN or other specified feeding or eating disorder) and 28 healthy adolescents participated in this study. Anatomical magnetic resonance imaging and clinical data were acquired at 3 time points within 2-year intervals over adolescence, with 31% average attrition between assessments. Using a region-of-interest approach, we assessed group differences in CT at baseline and over time, and tested whether between- and within-subject variations in CT were associated with the frequency of BN symptoms. Reduced CT in the right inferior frontal gyrus persisted over adolescence in BN compared to healthy adolescents, even in those who achieved full or partial remission. Within the BN group, between-subject variations in CT in the inferior and orbital frontal regions were inversely associated with specific BN symptoms, suggesting, on average over time, greater CT reductions in individuals with more frequent BN symptoms. Reduced CT in inferior frontal regions may contribute to illness persistence into adulthood. Reductions in the thickness of the inferior and orbital frontal regions may be markers of specific BN symptoms. Because our sample size precluded correcting for multiple comparisons, these findings should be replicated in a larger sample. Future study of functional changes in associated fronto-striatal circuits could identify potential circuit-based intervention targets. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms.

    Directory of Open Access Journals (Sweden)

    Nicolas Barraud

    Full Text Available The failure of antibiotic therapies to clear Pseudomonas aeruginosa lung infection, the key mortality factor for cystic fibrosis (CF patients, is partly attributed to the high tolerance of P. aeruginosa biofilms. Mannitol has previously been found to restore aminoglycoside sensitivity in Escherichia coli by generating a proton-motive force (PMF, suggesting a potential new strategy to improve antibiotic therapy and reduce disease progression in CF. Here, we used the commonly prescribed aminoglycoside tobramycin to select for P. aeruginosa persister cells during biofilm growth. Incubation with mannitol (10-40 mM increased tobramycin sensitivity of persister cells up to 1,000-fold. Addition of mannitol to pre-grown biofilms was able to revert the persister phenotype and improve the efficacy of tobramycin. This effect was blocked by the addition of a PMF inhibitor or in a P. aeruginosa mutant strain unable to metabolise mannitol. Addition of glucose and NaCl at high osmolarity also improved the efficacy of tobramycin although to a lesser extent compared to mannitol. Therefore, the primary effect of mannitol in reverting biofilm associated persister cells appears to be an active, physiological response, associated with a minor contribution of osmotic stress. Mannitol was tested against clinically relevant strains, showing that biofilms containing a subpopulation of persister cells are better killed in the presence of mannitol, but a clinical strain with a high resistance to tobramycin was not affected by mannitol. Overall, these results suggest that in addition to improvements in lung function by facilitating mucus clearance in CF, mannitol also affects antibiotic sensitivity in biofilms and does so through an active, physiological response.

  2. Increasing persistence in undergraduate science majors: a model for institutional support of underrepresented students.

    Science.gov (United States)

    Toven-Lindsey, Brit; Levis-Fitzgerald, Marc; Barber, Paul H; Hasson, Tama

    2015-01-01

    The 6-yr degree-completion rate of undergraduate science, technology, engineering, and mathematics (STEM) majors at U.S. colleges and universities is less than 40%. Persistence among women and underrepresented minorities (URMs), including African-American, Latino/a, Native American, and Pacific Islander students, is even more troubling, as these students leave STEM majors at significantly higher rates than their non-URM peers. This study utilizes a matched comparison group design to examine the academic achievement and persistence of students enrolled in the Program for Excellence in Education and Research in the Sciences (PEERS), an academic support program at the University of California, Los Angeles, for first- and second-year science majors from underrepresented backgrounds. Results indicate that PEERS students, on average, earned higher grades in most "gatekeeper" chemistry and math courses, had a higher cumulative grade point average, completed more science courses, and persisted in a science major at significantly higher rates than the comparison group. With its holistic approach focused on academics, counseling, creating a supportive community, and exposure to research, the PEERS program serves as an excellent model for universities interested in and committed to improving persistence of underrepresented science majors and closing the achievement gap. © 2015 B. Toven-Lindsey et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. A four-year follow-up controlled study of stress response and symptom persistence in Brazilian children and adolescents with attention deficit disorder and hyperactivity (ADHD).

    Science.gov (United States)

    Palma, Sonia Maria Motta; Natale, Ana Carolina Motta Palma; Calil, Helena Maria

    2015-12-15

    This study evaluated children and adolescents with Attention Deficit Disorder andHyperactivity Disorder (ADHD), reassessing them at a four-year follow-up. Their cortisol response to a stress stimulus was measured twice. ADHD symptom persistence, development of comorbidities, and psychostimulant usage were also reassessed. The initial sample consisted of 38 ADHD patients and 38 healthy controls, age ranging 6-14. At the follow-up, there were 37 ADHD patients and 22 healthy controls, age ranging 10-18. ADHD was classified as persistent if the patients fulfilled all DSM IV criteria for syndromic or subthreshold or had functional impairment. Salivary cortisol samples were collected prior to the application of a cognitive stressor (Continuous Performance Test - CPT), and at three time intervals afterwards at baseline and at the follow-up. Their reassessment showed that 75% had persistent symptoms, psychiatric comorbidities (oppositional defiant and behavioral disorders), functional and academic impairement. Only seven patients were on medication. The ADHD group's cortisol levels were lower than those measured four years earlier, but cortisol concentrations were similar for both ADHD and control groups at the four-year follow-up. The cortisol results suggest that HPA axis reactivity could be a marker differentiating ADHD from ADHD with comorbidities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Curcumin targets breast cancer stem-like cells with microtentacles that persist in mammospheres and promote reattachment.

    Science.gov (United States)

    Charpentier, Monica S; Whipple, Rebecca A; Vitolo, Michele I; Boggs, Amanda E; Slovic, Jana; Thompson, Keyata N; Bhandary, Lekhana; Martin, Stuart S

    2014-02-15

    Cancer stem-like cells (CSC) and circulating tumor cells (CTC) have related properties associated with distant metastasis, but the mechanisms through which CSCs promote metastasis are unclear. In this study, we report that breast cancer cell lines with more stem-like properties display higher levels of microtentacles (McTN), a type of tubulin-based protrusion of the plasma cell membrane that forms on detached or suspended cells and aid in cell reattachment. We hypothesized that CSCs with large numbers of McTNs would more efficiently attach to distant tissues, promoting metastatic efficiency. The naturally occurring stem-like subpopulation of the human mammary epithelial (HMLE) cell line presents increased McTNs compared with its isogenic non-stem-like subpopulation. This increase was supported by elevated α-tubulin detyrosination and vimentin protein levels and organization. Increased McTNs in stem-like HMLEs promoted a faster initial reattachment of suspended cells that was inhibited by the tubulin-directed drug, colchicine, confirming a functional role for McTNs in stem cell reattachment. Moreover, live-cell confocal microscopy showed that McTNs persist in breast stem cell mammospheres as flexible, motile protrusions on the surface of the mammosphere. Although exposed to the environment, they also function as extensions between adjacent cells along cell-cell junctions. We found that treatment with the breast CSC-targeting compound curcumin rapidly extinguished McTN in breast CSC, preventing reattachment from suspension. Together, our results support a model in which breast CSCs with cytoskeletal alterations that promote McTNs can mediate attachment and metastasis but might be targeted by curcumin as an antimetastatic strategy. ©2013 AACR.

  5. Near Infrared-Emitting Cr3+/Eu3+ Co-doped Zinc Gallogermanate Persistence Luminescent Nanoparticles for Cell Imaging

    Science.gov (United States)

    Wang, Qiaoqiao; Zhang, Shuyun; Li, Zhiwei; Zhu, Qi

    2018-02-01

    Near infrared (NIR)-emitting persistent luminescent nanoparticles have been developed as potential agents for bioimaging. However, synthesizing uniform nanoparticles with long afterglow for long-term imaging is lacking. Here, we demonstrated the synthesis of spinel structured Zn3Ga2Ge2O10:Cr3+ (ZGGO:Cr3+) and Zn3Ga2Ge2O10:Cr3+,Eu3+ (ZGGO:Cr3+,Eu3+) nanoparticles by a sol-gel method in combination with a subsequent reducing atmosphere-free calcination. The samples were investigated via detailed characterizations by combined techniques of XRD, TEM, STEM, selected area electron diffraction, photoluminescence excitation (PLE)/photoluminescence (PL) spectroscopy, and temperature-dependent PL analysis. The single-crystalline nanoparticles are homogeneous solid solution, possessing uniform cubic shape and lateral size of 80-100 nm. Upon UV excitation at 273 nm, ZGGO:Cr3+,Eu3+ exhibited a NIR emission band at 697 nm (2E → 4A2 transition of distorted Cr3+ ions in gallogermanate), in the absence of Eu3+ emission. NIR persistent luminescence of the sample can last longer than 7200 s and still hold intense intensity. Eu3+ incorporation increased the persistent luminescence intensity and the afterglow time of ZGGO:Cr3+, but it did not significantly affect the thermal stability. The obtained ZGGO:Cr3+,Eu3+-NH2 nanoparticles possessed an excellent imaging capacity for cells in vitro.

  6. Persistent Hiccups Following Stapedectomy

    Directory of Open Access Journals (Sweden)

    Aidonis I

    2010-10-01

    Full Text Available Objective: We report a case of a 37 year-old man who developed persistent hiccups after elective stapedectomy. Method and Results: The diagnostic approach is discussed as well as the non-pharmacologic and pharmacologic treatments and overall management. The aim is to stress that there is a variety of potential factors that can induce hiccups perioperatively and in cases like this a step by step approach must be taken. Conclusion: Persistent hiccups are very rare following stapedectomy, control of them is crucial for the successful outcome. The trigger may be more than one factors and the good response to treatment may be due to dealing successfully with more than one thing.

  7. Persistent Transmissible Gastroenteritis Virus Infection Enhances Enterotoxigenic Escherichia coli K88 Adhesion by Promoting Epithelial-Mesenchymal Transition in Intestinal Epithelial Cells.

    Science.gov (United States)

    Xia, Lu; Dai, Lei; Yu, Qinghua; Yang, Qian

    2017-11-01

    Transmissible gastroenteritis virus (TGEV) is a coronavirus characterized by diarrhea and high morbidity rates, and the mortality rate is 100% in piglets less than 2 weeks old. Pigs infected with TGEV often suffer secondary infection by other pathogens, which aggravates the severity of diarrhea, but the mechanisms remain unknown. Here, we hypothesized that persistent TGEV infection stimulates the epithelial-mesenchymal transition (EMT), and thus enterotoxigenic Escherichia coli (ETEC) can more easily adhere to generating cells. Intestinal epithelial cells are the primary targets of TGEV and ETEC infections. We found that TGEV can persistently infect porcine intestinal columnar epithelial cells (IPEC-J2) and cause EMT, consistent with multiple changes in key cell characteristics. Infected cells display fibroblast-like shapes; exhibit increases in levels of mesenchymal markers with a corresponding loss of epithelial markers; have enhanced expression levels of interleukin-1β (IL-1β), IL-6, IL-8, transforming growth factor β (TGF-β), and tumor necrosis factor alpha (TNF-α) mRNAs; and demonstrate increases in migratory and invasive behaviors. Additional experiments showed that the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways via TGF-β is critical for the TGEV-mediated EMT process. Cellular uptake is also modified in cells that have undergone EMT. TGEV-infected cells have higher levels of integrin α5 and fibronectin and exhibit enhanced ETEC K88 adhesion. Reversal of EMT reduces ETEC K88 adhesion and inhibits the expression of integrin α5 and fibronectin. Overall, these results suggest that TGEV infection induces EMT in IPEC-J2 cells, increasing the adhesion of ETEC K88 in the intestine and facilitating dual infection. IMPORTANCE Transmissible gastroenteritis virus (TGEV) causes pig diarrhea and is often followed by secondary infection by other pathogens. In this study, we showed

  8. Physiology, anaerobes, and the origin of mitosing cells 50 years on.

    Science.gov (United States)

    Martin, William F

    2017-12-07

    Endosymbiotic theory posits that some organelles or structures of eukaryotic cells stem from free-living prokaryotes that became endosymbionts within a host cell. Endosymbiosis has a long and turbulent history of controversy and debate going back over 100 years. The 1967 paper by Lynn Sagan (later Lynn Margulis) forced a reluctant field to take endosymbiotic theory seriously and to incorporate it into the fabric of evolutionary thinking. Margulis envisaged three cellular partners associating in series at eukaryotic origin: the host (an engulfing bacterium), the mitochondrion (a respiring bacterium), and the flagellum (a spirochaete), with lineages descended from that flagellated eukaryote subsequently acquiring plastids from cyanobacteria, but on multiple different occasions in her 1967 account. Today, the endosymbiotic origin of mitochondria and plastids (each single events, the data now say) is uncontested textbook knowledge. The host has been more elusive, recent findings identifying it as a member of the archaea, not as a sister group of the archaea. Margulis's proposal for a spirochaete origin of flagellae was abandoned by everyone except her, because no data ever came around to support the idea. Her 1967 proposal that mitochondria and plastids arose from different endosymbionts was novel. The paper presented an appealing narrative that linked the origin of mitochondria with oxygen in Earth history: cyanobacteria make oxygen, oxygen starts accumulating in the atmosphere about 2.4 billion years ago, oxygen begets oxygen-respiring bacteria that become mitochondria via symbiosis, followed by later (numerous) multiple, independent symbioses involving cyanobacteria that brought photosynthesis to eukaryotes. With the focus on oxygen, Margulis's account of eukaryote origin was however unprepared to accommodate the discovery of mitochondria in eukaryotic anaerobes. Today's oxygen narrative has it that the oceans were anoxic up until about 580 million years ago, while

  9. Inefficiency persistence and heterogeneity in Colombian electricity utilities

    International Nuclear Information System (INIS)

    Galán, Jorge E.; Pollitt, Michael G.

    2014-01-01

    The electricity reform in Colombia has exhibited gains in terms of reliability but its effects on firm efficiency and service quality have not been clear. Previous studies evaluating the performance of distribution companies after the reform have not found evidence of improvements, although large differences in efficiency have been found among firms. This suggests high inefficiency persistence and heterogeneity in the Colombian distribution sector. In this paper, we propose an extension of dynamic stochastic frontier models that accounts for unobserved heterogeneity in the inefficiency persistence and in the technology. The model incorporates total expenses, service quality and energy losses in an efficiency analysis of Colombian distributors over fifteen years after the reform. We identify the presence of high inefficiency persistence in the sector, and important differences between firms. In particular, rural companies and firms with small customers present low persistence and evidence the largest gains in efficiency during the period. However, increases in efficiency are only manifested during thelast five years when the main improvements in service quality and energy losses are presented. Overall, inefficiency persistence, customer density and consumption density are found to be important criteria to be considered for regulatory purposes. - Highlights: • We evaluate efficiency of Colombian electricity distributors after the reform. • We use a stochastic frontier model with dynamic effects and heterogeneity. • We find high inefficiency persistence but important differences among firms. • High persistent and low efficient firms should draw the attention of the regulator. • Recent regulation in quality has increased not only efficiency but also tariffs

  10. Treatment of acral persistent papular mucinosis with electrocoagulation.

    Science.gov (United States)

    André Jorge, Flávia; Mimura Cortez, Tatiana; Guadalini Mendes, Fabiana; Esther Alencar Marques, Mariângela; Amante Miot, Hélio

    2011-01-01

    Acral persistent papular mucinosis is a rare localized form of lichen myxedematosus with few case reports and no documented therapeutic options. To report full resolution of acral persistent papular mucinosis after electrocoagulation. Case report of a 51-year-old white female diagnosed with an acral persistent papular mucinosis. The clinical and histopathologic features, treatment provided, and response to treatment are detailed. Acral persistent papular mucinosis presented as multiple asymptomatic normochromic papules on the wrists. Treatment with topical and intralesional steroids was unsatisfactory. Gentle electrocoagulation led to complete resolution of the lesions and negligible scarring. The favorable results remained for 6 months of follow-up, and no new lesions have emerged. Our case of acral persistent papular mucinosis was successfully treated with electrocoagulation and long-lasting, excellent cosmetic results.

  11. Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

    Science.gov (United States)

    Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

    2017-08-01

    To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

  12. Persistent infection with ebola virus under conditions of partial immunity.

    Science.gov (United States)

    Gupta, Manisha; Mahanty, Siddhartha; Greer, Patricia; Towner, Jonathan S; Shieh, Wun-Ju; Zaki, Sherif R; Ahmed, Rafi; Rollin, Pierre E

    2004-01-01

    Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective immunity are not well defined. Using a mouse model, we determined the role of the immune system in clearance of and protection against Ebola virus. All CD8 T-cell-deficient mice succumbed to subcutaneous infection and had high viral antigen titers in tissues, whereas mice deficient in B cells or CD4 T cells cleared infection and survived, suggesting that CD8 T cells, independent of CD4 T cells and antibodies, are critical to protection against subcutaneous Ebola virus infection. B-cell-deficient mice that survived the primary subcutaneous infection (vaccinated mice) transiently depleted or not depleted of CD4 T cells also survived lethal intraperitoneal rechallenge for >/==" BORDER="0">25 days. However, all vaccinated B-cell-deficient mice depleted of CD8 T cells had high viral antigen titers in tissues following intraperitoneal rechallenge and died within 6 days, suggesting that memory CD8 T cells by themselves can protect mice from early death. Surprisingly, vaccinated B-cell-deficient mice, after initially clearing the infection, were found to have viral antigens in tissues later (day 120 to 150 post-intraperitoneal infection). Furthermore, following intraperitoneal rechallenge, vaccinated B-cell-deficient mice that were transiently depleted of CD4 T cells had high levels of viral antigen in tissues earlier (days 50 to 70) than vaccinated undepleted mice. This demonstrates that under certain immunodeficiency conditions, Ebola virus can persist and that loss of primed CD4 T cells accelerates the course of persistent infections. These data show that CD8 T cells play an important role in protection against acute disease, while both CD4 T cells and antibodies are required for long-term protection, and they provide evidence of persistent infection by Ebola virus suggesting

  13. Hyperthyroidism as a cause of persistent vomiting.

    Science.gov (United States)

    Hoogendoorn, E H; Cools, B M

    2004-09-01

    A 32-year-old woman presented with persistent vomiting, epigastric pain and weight loss. A sinus tachycardia was the clue to the diagnosis of hyperthyroidism due to Graves' disease. On treatment with propylthiouracil and a beta-blocking agent, her symptoms resolved within one day, even though her free thyroxine level was still high. Hyperthyroidism is an uncommon, but previously reported cause of persistent vomiting.

  14. Hyperthyroidism as a cause of persistent vomiting.

    OpenAIRE

    Hoogendoorn, E.H.; Cools, B.M.

    2004-01-01

    A 32-year-old woman presented with persistent vomiting, epigastric pain and weight loss. A sinus tachycardia was the clue to the diagnosis of hyperthyroidism due to Graves' disease. On treatment with propylthiouracil and a beta-blocking agent, her symptoms resolved within one day, even though her free thyroxine level was still high. Hyperthyroidism is an uncommon, but previously reported cause of persistent vomiting.

  15. Impact of innate and environmental factors on wheezing persistence during childhood.

    Science.gov (United States)

    Just, Jocelyne; Belfar, Samira; Wanin, Stéphanie; Pribil, Céline; Grimfeld, Alain; Duru, Gérard

    2010-05-01

    Persistent asthma in adults starts often early in childhood and is associated with alterations in respiratory function that occur early in life. The aim of this study was to evaluate the importance of innate and environmental factors associated with occurrence of asthma during childhood in a population of recurrent wheezing infants followed prospectively. A cohort of infants less than 30 months old with recurrent wheezing was established in order to assess severity of respiratory symptoms and to look for the presence of atopy and environmental risk factors. At the age of 6 years, they were reevaluated with respect to remission or persistence of wheezing over the previous 12-month period. Data were available for 219 subjects aged 15 +/- 5 months. In 27% of the infants with recurrent wheeze, wheezing persisted until the age of 6 years. In multivariate analysis, stepwise logit analysis showed that the risk factors for persistent wheezing are eosinophilia >or=470/mm(3), allergenic sensitization, and a father with asthma. Environmental factors present during the first year of life that protect from persistence of wheezing are ( 1 ) breastfeeding for longer than 3 months, ( 2 ) pets at home, and ( 3 ) >or=3 siblings. The detection rate for persistent wheezing in this model is 72%. The persistence score showed good specificity 91% but low sensitivity 35%. This study confirms the role of atopic host factors on wheezing persistence during childhood and detected protective environmental factors.

  16. Predictive features of persistent activity emergence in regular spiking and intrinsic bursting model neurons.

    Directory of Open Access Journals (Sweden)

    Kyriaki Sidiropoulou

    Full Text Available Proper functioning of working memory involves the expression of stimulus-selective persistent activity in pyramidal neurons of the prefrontal cortex (PFC, which refers to neural activity that persists for seconds beyond the end of the stimulus. The mechanisms which PFC pyramidal neurons use to discriminate between preferred vs. neutral inputs at the cellular level are largely unknown. Moreover, the presence of pyramidal cell subtypes with different firing patterns, such as regular spiking and intrinsic bursting, raises the question as to what their distinct role might be in persistent firing in the PFC. Here, we use a compartmental modeling approach to search for discriminatory features in the properties of incoming stimuli to a PFC pyramidal neuron and/or its response that signal which of these stimuli will result in persistent activity emergence. Furthermore, we use our modeling approach to study cell-type specific differences in persistent activity properties, via implementing a regular spiking (RS and an intrinsic bursting (IB model neuron. We identify synaptic location within the basal dendrites as a feature of stimulus selectivity. Specifically, persistent activity-inducing stimuli consist of activated synapses that are located more distally from the soma compared to non-inducing stimuli, in both model cells. In addition, the action potential (AP latency and the first few inter-spike-intervals of the neuronal response can be used to reliably detect inducing vs. non-inducing inputs, suggesting a potential mechanism by which downstream neurons can rapidly decode the upcoming emergence of persistent activity. While the two model neurons did not differ in the coding features of persistent activity emergence, the properties of persistent activity, such as the firing pattern and the duration of temporally-restricted persistent activity were distinct. Collectively, our results pinpoint to specific features of the neuronal response to a given

  17. Persistence of radiation-induced chromosome aberrations in a long-term cell culture.

    Science.gov (United States)

    Duran, Assumpta; Barquinero, Joan Francesc; Caballín, María Rosa; Ribas, Montserrat; Barrios, Leonardo

    2009-04-01

    The aim of the present study was to evaluate the persistence of chromosome aberrations induced by X rays. FISH painting and mFISH techniques were applied to long-term cultures of irradiated cells. With painting, at 2 Gy the frequency of apparently simple translocations remained almost invariable during all the culture, whereas at 4 Gy a rapid decline was observed between the first and the second samples, followed by a slight decrease until the end of the culture. Apparently simple dicentrics and complex aberrations disappeared after the first sample at 2 and 4 Gy. By mFISH, at 2 Gy the frequency of complete plus one-way translocations remained invariable between the first and last sample, but at 4 Gy a 60% decline was observed. True incomplete simple translocations disappeared at 2 and 4 Gy, indicating that incompleteness could be a factor to consider when the persistence of translocations is analyzed. The analysis by mFISH showed that the frequency of complex aberrations and their complexity increased with dose and tended to disappear in the last sample. Our results indicate that the influence of dose on the decrease in the frequency of simple translocations with time postirradiation cannot be fully explained by the disappearance of true incomplete translocations and complex aberrations. The chromosome involvement was random for radiation-induced exchange aberrations and non-random for total aberrations. Chromosome 7 showed the highest deviations from expected, being less and more involved than expected in the first and last samples, respectively. Some preferential chromosome-chromosome associations were observed, including a coincidence with a cluster from radiogenic chromosome aberrations described in other studies.

  18. Persistence of mucosal T-cell responses to herpes simplex virus type 2 in the female genital tract.

    Science.gov (United States)

    Posavad, C M; Zhao, L; Mueller, D E; Stevens, C E; Huang, M L; Wald, A; Corey, L

    2015-01-01

    Relatively little is known about the human T-cell response to herpes simplex virus type 2 (HSV-2) in the female genital tract, a major site of heterosexual HSV-2 acquisition, transmission, and reactivation. In order to understand the role of local mucosal immunity in HSV-2 infection, T-cell lines were expanded from serial cervical cytobrush samples from 30 HSV-2-infected women and examined for reactivity to HSV-2. Approximately 3% of the CD3+ T cells isolated from the cervix were HSV-2 specific and of these, a median of 91.3% were CD4+, whereas a median of 3.9% were CD8+. HSV-2-specific CD4+ T cells expanded from the cervix were not only more frequent than CD8+ T cells but also exhibited greater breadth in terms of antigenic reactivity. T cells directed at the same HSV-2 protein were often detected in serial cervical cytobrush samples and in blood. Thus, broad and persistent mucosal T-cell responses to HSV-2 were detected in the female genital tract of HSV-2+ women suggesting that these cells are resident at the site of HSV-2 infection. Understanding the role of these T cells at this biologically relevant site will be central to the elucidation of adaptive immune mechanisms involved in controlling HSV-2 disease.

  19. Cell-Specific PKM Isoforms Contribute to the Maintenance of Different Forms of Persistent Long-Term Synaptic Plasticity.

    Science.gov (United States)

    Hu, Jiangyuan; Adler, Kerry; Farah, Carole Abi; Hastings, Margaret H; Sossin, Wayne S; Schacher, Samuel

    2017-03-08

    -term plasticity. This study provides evidence that the cell-specific activities of different PKM isoforms generated from PKCs by calpain-mediated cleavage maintain two forms of persistent synaptic plasticity, which are the cellular analogs of two forms of long-term memory. Moreover, we found that the activation of specific calpains depends on the features of the stimuli evoking the different forms of synaptic plasticity. Given the recent controversy over the role of PKMζ maintaining memory, these findings are significant in identifying roles of multiple PKMs in the retention of memory. Copyright © 2017 the authors 0270-6474/17/372746-18$15.00/0.

  20. Conditions of persistent oil on beaches in Prince William Sound 26 years after the Exxon Valdez spill

    Science.gov (United States)

    Lindeberg, Mandy R.; Maselko, Jacek; Heintz, Ron A.; Fugate, Corey J.; Holland, Larry

    2018-01-01

    On March 24, 1989, the Exxon Valdez grounded on Bligh Reef in Prince William Sound, Alaska, spilling an estimated 10.8 million gallons of crude oil. Contrary to early projections, subsequent studies over several decades have shown subsurface oil persisting on impacted beaches. Here we present findings from a lingering oil survey conducted during the summer of 2015 at a small set of beaches in Prince William Sound known to have persistent subsurface Exxon Valdez oil. The objectives of the survey were to estimate how much oil remains at these sites, the oil composition, and oil retention rates compared to previous studies. Results from the survey found lingering oil was present at 8 of 9 sites that were revisited. Surveys revealed little evidence of change in oil area or mass over the last 14 years, nor has there been a change in the distribution of oiling intensities or their location on the beach. Detailed analysis of the oil indicated it has not weathered since 2001. Subsurface oils collected in 2015 have enriched concentrations of phenanthrenes and chrysenes relative to oil originating in the cargo hold indicating that buried oil has retained some toxic potential over the last two decades, but it is not currently bioavailable. Subsurface oil appears to be sequestered in sediments and protected from hydrological washing and low oxygen and nutrient levels inhibiting biodegradation. These findings are consistent with previous surveys and predictive geomorphic models suggesting the estimated 0.6% Exxon Valdez oil remaining is sequestered and not bioavailable unless disturbed and will likely persist in the environment on a decadal scale.

  1. A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2015-03-01

    Full Text Available A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing.

  2. Spike persistence and normalization in benign epilepsy with centrotemporal spikes - Implications for management.

    Science.gov (United States)

    Kim, Hunmin; Kim, Soo Yeon; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Dlugos, Dennis J

    2018-05-10

    This study was performed 1) to determine the timing of spike normalization in patients with benign epilepsy with centrotemporal spikes (BECTS); 2) to identify relationships between age of seizure onset, age of spike normalization, years of spike persistence and treatment; and 3) to assess final outcomes between groups of patients with or without spikes at the time of medication tapering. Retrospective analysis of BECTS patients confirmed by clinical data, including age of onset, seizure semiology and serial electroencephalography (EEG) from diagnosis to remission. Age at spike normalization, years of spike persistence, and time of treatment onset to spike normalization were assessed. Final seizure and EEG outcome were compared between the groups with or without spikes at the time of AED tapering. One hundred and thirty-four patients were included. Mean age at seizure onset was 7.52 ± 2.11 years. Mean age at spike normalization was 11.89 ± 2.11 (range: 6.3-16.8) years. Mean time of treatment onset to spike normalization was 4.11 ± 2.13 (range: 0.24-10.08) years. Younger age of seizure onset was correlated with longer duration of spike persistence (r = -0.41, p < 0.001). In treated patients, spikes persisted for 4.1 ± 1.95 years, compared with 2.9 ± 1.97 years in untreated patients. No patients had recurrent seizures after AED was discontinued, regardless of the presence/absence of spikes at time of AED tapering. Years of spike persistence was longer in early onset BECTS patients. Treatment with AEDs did not shorten years of spike persistence. Persistence of spikes at time of treatment withdrawal was not associated with seizure recurrence. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. Persistent currents in three-dimensional shell-doped nanorings

    International Nuclear Information System (INIS)

    Ning, Xu; Jian-Wen, Ding; Hong-Bo, Chen; Ming-Ming, Ma

    2009-01-01

    The persistent current in three-dimensional (P × N 2 ) nanorings as a function of the unit cell number (P), the channel number (M = N 2 ), surface disorder (ξ), and temperature (T) is theoretically investigated in terms of rotational symmetry. On the whole, the typical current increases linearly with √M but decreases exponentially with P, while wide fluctuations exist therein. In the presence of surface disorder, the persistent current decreases with ξ in the regime of weak disorder but increases in the regime of strong disorder. In addition, it is found that the persistent current in perfect rings decreases exponentially with temperature even at T * , while in most disorder rings, the typical current decreases slightly with temperature at T *

  4. HIV Persistence in Adipose Tissue Reservoirs.

    Science.gov (United States)

    Couturier, Jacob; Lewis, Dorothy E

    2018-02-01

    The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and

  5. Real-world persistence with fingolimod for the treatment of multiple sclerosis: A systematic review and meta-analysis.

    Science.gov (United States)

    Kantor, Daniel; Johnson, Kristen; Vieira, Maria Cecilia; Signorovitch, James; Li, Nanxin; Gao, Wei; Koo, Valerie; Duchesneau, Emilie; Herrera, Vivian

    2018-05-15

    To systematically review reports of fingolimod persistence in the treatment of relapsing-remitting multiple sclerosis (RRMS) across data sources and practice settings, and to develop a consensus estimate of the 1-year real-world persistence rate. A systematic literature review was conducted (MEDLINE, EMBASE, and abstracts from selected conferences [2013-2015]) to identify observational studies reporting 1-year fingolimod persistence among adult patients with RRMS (sample size ≥50). A random-effects meta-analysis was performed to estimate a synthesized 1-year persistence rate and to assess heterogeneity across studies. Of 527 publications identified, 25 real-world studies reporting 1-year fingolimod persistence rates were included. The studies included patients from different data sources (e.g., administrative claims, electronic medical records, or registries), used different definitions of persistence (e.g., based on prescriptions refills, patient report, or prescription orders), and spanned multiple geographic regions. Reported 1-year persistence rates ranged from 72%-100%, and exhibited statistical evidence of heterogeneity (I 2  = 93% of the variability due to heterogeneity across studies). The consensus estimate of the 1-year persistence rate was 82% (95% confidence interval: 79%-85%). Across heterogeneous study designs and patient populations found in real-world studies, the consensus 1-year fingolimod persistence rate exceeded 80%, consistent with persistence rates identified in the recently-completed trial, PREFERMS. Copyright © 2018. Published by Elsevier B.V.

  6. Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy.

    Directory of Open Access Journals (Sweden)

    Wooseong Kim

    Full Text Available Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7. In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 108 CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.

  7. Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy.

    Science.gov (United States)

    Kim, Wooseong; Conery, Annie L; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Ausubel, Frederick M; Mylonakis, Eleftherios

    2015-01-01

    Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA) persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7). In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 108 CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.

  8. Nanohybrids with Magnetic and Persistent Luminescence Properties for Cell Labeling, Tracking, In Vivo Real-Time Imaging, and Magnetic Vectorization.

    Science.gov (United States)

    Teston, Eliott; Maldiney, Thomas; Marangon, Iris; Volatron, Jeanne; Lalatonne, Yoann; Motte, Laurence; Boisson-Vidal, Catherine; Autret, Gwennhael; Clément, Olivier; Scherman, Daniel; Gazeau, Florence; Richard, Cyrille

    2018-04-01

    Once injected into a living organism, cells diffuse or migrate around the initial injection point and become impossible to be visualized and tracked in vivo. The present work concerns the development of a new technique for therapeutic cell labeling and subsequent in vivo visualization and magnetic retention. It is hypothesized and subsequently demonstrated that nanohybrids made of persistent luminescence nanoparticles and ultrasmall superparamagnetic iron oxide nanoparticles incorporated into a silica matrix can be used as an effective nanoplatform to label therapeutic cells in a nontoxic way in order to dynamically track them in real-time in vitro and in living mice. As a proof-of-concept, it is shown that once injected, these labeled cells can be visualized and attracted in vivo using a magnet. This first step suggests that these nanohybrids represent efficient multifunctional nanoprobes for further imaging guided cell therapies development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Association of hypovitaminosis Dwith persistent non-specific musculoskeletal pains

    International Nuclear Information System (INIS)

    Alam, H.M.A.; Kamran, M.; Rehman, S.U.; Khan, D.A.; Hussain, K.

    2017-01-01

    The study was conducted in Pakistani population to find association of vitamin D deficiency with persistent non-specific musculoskeletal pains by comparing with pain free controls. Study Design: Case control study. Material and Methods: Patients aged 12 years or more presenting to Medical OPD with persistent nonspecific musculoskeletal pains for more than 3 months were selected as cases, while healthy individuals served as controls Results: A total of 60 cases (patients with persistent non-specific pains) presenting to medical outpatients department at Military Hospital Rawalpindi and 60 controls were studied. Mean age of cases was 43.9 +- 14.0 years and amongst controls were 33.2 +- 17.8 years. Mean serum vitamin D level of 32.8 nmol/L was reported in cases whereas mean serum vitamin D level amongst controls was 26.7 +- 17.8 nmol/L. Hypovitaminosis D amongst cases and controls was 86.6% and 95% respectively. The proportion of vitamin D deficiency did not differ significantly as compared to controls. There was non-significant difference in proportion of deficiency amongst cases and controls. Conclusion: Overall there was no association between persistent non-specific musculoskeletal pains and vitamin D deficiency. (author)

  10. Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

    Directory of Open Access Journals (Sweden)

    Michael E. Hasselmo

    2008-01-01

    Full Text Available The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.

  11. WWC Review of the Report "Freshman Year Financial Aid Nudges: An Experiment to Increase FAFSA Renewal and College Persistence." What Works Clearinghouse Single Study Review

    Science.gov (United States)

    What Works Clearinghouse, 2014

    2014-01-01

    The 2014 study, Freshman Year Financial Aid Nudges: An Experiment to Increase FAFSA Renewal and College Persistence, measured the impact of sending text message reminders regarding annual Free Application for Federal Student Aid (FAFSA) renewal to first-year college students who were already receiving financial aid. The study sample included 808…

  12. Interaction between Galectin-9/TIM-3 pathway and follicular helper CD4+ T cells contributes to viral persistence in chronic hepatitis C.

    Science.gov (United States)

    Zhuo, Ya; Zhang, Yi-Fu; Wu, Hong-Jie; Qin, Lei; Wang, Yan-Ping; Liu, A-Min; Wang, Xin-Hong

    2017-10-01

    Both Galectin 9 (Gal-9)/T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) pathway and follicular helper CD4 + T (Tfh) cells play important roles in persistent hepatitis C virus (HCV) infection. Thus, we aimed to investigate the regulatory role of interaction between Gal-9/TIM-3 pathway and Tfh cells in chronic hepatitis C. A total of 44 chronic hepatitis C patients and 19 normal controls (NCs) were enrolled in this study. Purified CD4 + T cells were cultured by TIM-3 Fc protein, recombinant Gal-9, or IL-21 for 48h. TIM-3 expression, Tfh proportion, and IL-21 production was measured, respectively. The immunomodulatory role of Gal-9/TIM-3 and IL-21 was also investigated in HCV cell culture system in vitro. We found that the percentage corresponding to both TIM-3-positive and CXCR5 + ICOS + Tfh cells within CD4 + T cells, which correlated with HCV RNA replication, was significantly elevated in patients with chronic hepatitis C in comparison with those in NCs. Moreover, blockade of Gal-9/TIM-3 pathway by TIM-3 Fc protein increased Tfh cells proportion, IL-21 mRNA and protein expression within purified CD4 + T cells, while activation of Gal-9/TIM-3 signaling by Gal-9 stimulation decreased IL-21 production in both patients with chronic HCV infection and healthy individuals. Meanwhile, high concentrations (100 and 200ng/mL) of IL-21 stimulation also elevated TIM-3 expression on CD4 + T cells in chronic hepatitis C. Furthermore, TIM-3 blockage and IL-21 stimulation suppressed mRNA expressions of HCV-induced antiviral proteins (myxovirus resistance A and oligoadenylate synthetase) in Huh7.5 cells without affecting viral replication in HCV cell culture system. The interaction between Gal-9/TIM-3 pathway and Tfh cells contributed to viral persistent in chronic HCV infection, which might be pivotal for development of new therapeutic approaches for chronic hepatitis C. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Bacterial biofilm mechanical properties persist upon antibiotic treatment and survive cell death

    International Nuclear Information System (INIS)

    Zrelli, K; Galy, O; Henry, N; Latour-Lambert, P; Ghigo, J M; Beloin, C; Kirwan, L

    2013-01-01

    Bacteria living on surfaces form heterogeneous three-dimensional consortia known as biofilms, where they exhibit many specific properties one of which is an increased tolerance to antibiotics. Biofilms are maintained by a polymeric network and display physical properties similar to that of complex fluids. In this work, we address the question of the impact of antibiotic treatment on the physical properties of biofilms based on recently developed tools enabling the in situ mapping of biofilm local mechanical properties at the micron scale. This approach takes into account the material heterogeneity and reveals the spatial distribution of all the small changes that may occur in the structure. With an Escherichia coli biofilm, we demonstrate using in situ fluorescent labeling that the two antibiotics ofloxacin and ticarcillin—targeting DNA replication and membrane assembly, respectively—induced no detectable alteration of the biofilm mechanical properties while they killed the vast majority of the cells. In parallel, we show that a proteolytic enzyme that cleaves extracellular proteins into short peptides, but does not alter bacterial viability in the biofilm, clearly affects the mechanical properties of the biofilm structure, inducing a significant increase of the material compliance. We conclude that conventional biofilm control strategy relying on the use of biocides targeting cells is missing a key target since biofilm structural integrity is preserved. This is expected to efficiently promote biofilm resilience, especially in the presence of persister cells. In contrast, the targeting of polymer network cross-links—among which extracellular proteins emerge as major players—offers a promising route for the development of rational multi-target strategies to fight against biofilms. (paper)

  14. Bacterial biofilm mechanical properties persist upon antibiotic treatment and survive cell death

    Science.gov (United States)

    Zrelli, K.; Galy, O.; Latour-Lambert, P.; Kirwan, L.; Ghigo, J. M.; Beloin, C.; Henry, N.

    2013-12-01

    Bacteria living on surfaces form heterogeneous three-dimensional consortia known as biofilms, where they exhibit many specific properties one of which is an increased tolerance to antibiotics. Biofilms are maintained by a polymeric network and display physical properties similar to that of complex fluids. In this work, we address the question of the impact of antibiotic treatment on the physical properties of biofilms based on recently developed tools enabling the in situ mapping of biofilm local mechanical properties at the micron scale. This approach takes into account the material heterogeneity and reveals the spatial distribution of all the small changes that may occur in the structure. With an Escherichia coli biofilm, we demonstrate using in situ fluorescent labeling that the two antibiotics ofloxacin and ticarcillin—targeting DNA replication and membrane assembly, respectively—induced no detectable alteration of the biofilm mechanical properties while they killed the vast majority of the cells. In parallel, we show that a proteolytic enzyme that cleaves extracellular proteins into short peptides, but does not alter bacterial viability in the biofilm, clearly affects the mechanical properties of the biofilm structure, inducing a significant increase of the material compliance. We conclude that conventional biofilm control strategy relying on the use of biocides targeting cells is missing a key target since biofilm structural integrity is preserved. This is expected to efficiently promote biofilm resilience, especially in the presence of persister cells. In contrast, the targeting of polymer network cross-links—among which extracellular proteins emerge as major players—offers a promising route for the development of rational multi-target strategies to fight against biofilms.

  15. Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx.

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    Michael Eschbaumer

    Full Text Available In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated were challenged with FMDV A24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467 had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response-such as chemokines, cytokines and genes regulating T and B cells-were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97, indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E2 production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.

  16. Microbial Biofilms: Persisters, Tolerance and Dosing

    Science.gov (United States)

    Cogan, N. G.

    2005-03-01

    Almost all moist surfaces are colonized by microbial biofilms. Biofilms are implicated in cross-contamination of food products, biofouling, medical implants and various human infections such as dental cavities, ulcerative colitis and chronic respiratory infections. Much of current research is focused on the recalcitrance of biofilms to typical antibiotic and antimicrobial treatments. Although the polymer component of biofilms impedes the penetration of antimicrobials through reaction-diffusion limitation, this does not explain the observed tolerance, it merely delays the action of the agent. Heterogeneities in growth-rate also slow the eradication of the bacteria since most antimicrobials are far less effective for non-growing, or slowly growing bacteria. This also does not fully describe biofilm tolerance, since heterogeneities arr primairly a result of nutrient consumption. In this investigation, we describe the formation of `persister' cells which neither grow nor die in the presence of antibiotics. We propose that the cells are of a different phenotype than typical bacterial cells and the expression of the phenotype is regulated by the growth rate and the antibiotic concentration. We describe several experiments which describe the dynamics of persister cells and which motivate a dosing protocol that calls for periodic dosing of the population. We then introduce a mathematical model, which describes the effect of such a dosing regiment and indicates that the relative dose/withdrawal times are important in determining the effectiveness of such a treatment. A reduced model is introduced and the similar behavior is demonstrated analytically.

  17. A 20-year study of persistence of lower urinary tract symptoms and urinary incontinence in young women treated in childhood.

    Science.gov (United States)

    Petrangeli, F; Capitanucci, M L; Marciano, A; Mosiello, G; Alvaro, R; Zaccara, A; Finazzi-Agro, E; De Gennaro, M

    2014-06-01

    To determine whether urinary incontinence (UI) and lower urinary tract symptoms (LUTS) persist over years, patients treated for UI and LUTS in childhood were re-evaluated in adulthood. Forty-seven women (cases) treated in childhood for daytime UI/LUTS (group A) and nocturnal enuresis (group B) self-completed (average age: 24.89 ± 3.5 years) the International Consultation on Incontinence Questionnaire for Female with LUTS (ICIQ-FLUTS). ICIQ-FLUTS was self-administered to 111 healthy women (average age: 23 ± 5.1 years) from a nursing school as a control group. Data obtained from ICIQ-FLUTS and quality of life (QoL) score (0-10) were compared (Fisher's exact test) between patients and controls, and between group A (n = 28) and group B (n = 19). Prevalence of LUTS was higher in patients than in controls. The difference between patients and controls was statistically significant (p = 0.0001) for UI (34% vs. 7%) and feeling of incomplete bladder emptying (49% vs. 28%). QoL score was >5 in 59% of patients and 1% of controls (p = 0.0001). No significant differences were found between groups A and B. UI and LUTS are confirmed in young women who suffered for the same condition in childhood. Longitudinal studies are needed to assess if these symptoms persist or are newly onset. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  18. Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid

    International Nuclear Information System (INIS)

    Wnek, S.M.; Medeiros, M.K.; Eblin, K.E.; Gandolfi, A.J.

    2009-01-01

    Malignant transformation was demonstrated in UROtsa cells following 52-weeks of exposure to 50 nM monomethylarsonous acid (MMA III ); the result was the malignantly transformed cell line, URO-MSC. URO-MSC cells were used to study the induction of DNA damage and the alteration of DNA repair enzymes in both the presence of MMA III [URO-MSC(+)] and after subsequent removal of MMA III [URO-MSC(-)] following chronic, low-level exposure. In the presence of MMA III , URO-MSC(+) cells demonstrated a sustained increase in DNA damage following 12-weeks of exposure; in particular, a significant increase in DNA single-strand breaks at 12-weeks of exposure consistently elevated through 52 weeks. The persistence of DNA damage in URO-MSC cells was assessed after a 2-week removal of MMA III . URO-MSC(-) cells demonstrated a decrease in DNA damage compared to URO-MSC(+); however, DNA damage in URO-MSC(-) remained significantly elevated when compared to untreated UROtsa and increased in a time-dependent manner. Reactive oxygen species (ROS) were demonstrated to be a critical component in the generation of DNA damage determined through the incubation of ROS scavengers with URO-MSC cells. Poly (ADP-ribose) polymerase (PARP) is a key repair enzyme in DNA single-strand break repair. URO-MSC(+) resulted in a slight increase in PARP activity after 36-weeks of MMA III exposure, suggesting the presence of MMA III is inhibiting the increase in PARP activity. In support, PARP activity in URO-MSC(-) increased significantly, coinciding with a subsequent decrease in DNA damage demonstrated in URO-MSC(-) compared to URO-MSC(+). These data demonstrate that chronic, low-level exposure of UROtsa cells to 50 nM MMA III results in: the induction of DNA damage that remains elevated upon removal of MMA III ; increased levels of ROS that play a role in MMA III induced-DNA damage; and decreased PARP activity in the presence of MMA III .

  19. Trends in the treatment changes and medication persistence of chronic myeloid leukemia in Taiwan from 1997 to 2007: a longitudinal population database analysis

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    Chang Chao-Sung

    2012-10-01

    Full Text Available Abstract Background Few studies have examined the longitudinal changes in the patterns, selection, and utilization of treatments for chronic myeloid leukemia (CML in routine clinical practice since the introduction of imatinib. Therefore, we investigated the trends in CML therapy, including changes, patterns, and persistence to imatinib therapy among patients with newly diagnosed CML. Methods We conducted a cross-sectional and longitudinal analysis of 11 years of claims data for patients with newly diagnosed CML included in the Taiwan National Health Insurance program. Pharmacy and diagnosis claims for newly diagnosed CML recorded between 1997 and 2007 year were extracted from the database. Annual overall use, new use of CML therapy, and persistence to imatinib therapy were estimated. The Anatomical Therapeutic Chemical codes for CML therapy [i.e., imatinib and conventional therapy: busulfan, hydroxyurea, interferon-α (IFNα, and cytarabine], and the process code for hematopoietic stem cell transplantation were used to categorize treatment patterns. Associations with patients characteristics were analyzed by multivariate logistic regression. Results Overall, the proportion of patients with newly diagnosed CML to all patients with CML increased by approximately 4-fold between 1998 and 2007. There were steady increases in the proportions of all treated patients and those starting therapy from 2003 to 2007. Fewer comorbid conditions and lower severity of CML were associated with treatment initiation. Medication persistence varied according to treatment duration, as 38.7% patients continued imatinib for ≥ 18 months without interruption but only 7.7% continued imatinib for ≥ 5 years. Factors associated with persistence to imatinib therapy were removal of the need for prior authorization for imatinib, and prior use of hydroxyurea and IFNα, whereas having undergone hematopoietic stem cell transplantation led to reduced likelihood

  20. Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells.

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    Shanaz A Ghandhi

    Full Text Available We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI. We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI.

  1. Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells.

    Science.gov (United States)

    Ghandhi, Shanaz A; Turner, Helen C; Shuryak, Igor; Dugan, Gregory O; Bourland, J Daniel; Olson, John D; Tooze, Janet A; Morton, Shad R; Batinic-Haberle, Ines; Cline, J Mark; Amundson, Sally A

    2018-01-01

    We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN) assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI. We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI.

  2. Extending and implementing the Persistent ID pillars

    Science.gov (United States)

    Car, Nicholas; Golodoniuc, Pavel; Klump, Jens

    2017-04-01

    The recent double decade anniversary of scholarly persistent identifier use has triggered journal special editions such as "20 Years of Persistent Identifiers". For such a publication, it is apt to consider the longevity of some persistent identifier (PID) mechanisms (Digital Object Identifiers) and the partial disappearance of others (Life Sciences IDs). We have previously postulated a set of "PID Pillars" [1] which are design principles aimed at ensuring PIDs can survive technology and social change and thus persist for the long term that we have drawn from our observations of PIDs at work over many years. The principles: describe how to ensure identifiers' system and organisation independence; codify the delivery of essential PID system functions; mandate a separation of PID functions from data delivery mechanisms; and require generation of policies detailing how change is handled. In this presentation, first we extend on our previous work of introducing the pillars by refining their descriptions, giving specific suggestions for each and presenting some work that addresses them. Second, we propose a baseline data model for persistent identifiers that, if used, would assist the separation of PID metadata and PID system functioning. This would allow PID system function specifics to change over time (e.g. resolver services or even resolution protocols) and yet preserve the PIDs themselves. Third, we detail our existing PID system — the PID Service [2] — that partially implements the pillars and describe both its successes and shortcomings. Finally, we describe our planned next-generation system that will aim to use the baseline data model and fully implement the pillars.

  3. Biomorphic Multi-Agent Architecture for Persistent Computing

    Science.gov (United States)

    Lodding, Kenneth N.; Brewster, Paul

    2009-01-01

    A multi-agent software/hardware architecture, inspired by the multicellular nature of living organisms, has been proposed as the basis of design of a robust, reliable, persistent computing system. Just as a multicellular organism can adapt to changing environmental conditions and can survive despite the failure of individual cells, a multi-agent computing system, as envisioned, could adapt to changing hardware, software, and environmental conditions. In particular, the computing system could continue to function (perhaps at a reduced but still reasonable level of performance) if one or more component( s) of the system were to fail. One of the defining characteristics of a multicellular organism is unity of purpose. In biology, the purpose is survival of the organism. The purpose of the proposed multi-agent architecture is to provide a persistent computing environment in harsh conditions in which repair is difficult or impossible. A multi-agent, organism-like computing system would be a single entity built from agents or cells. Each agent or cell would be a discrete hardware processing unit that would include a data processor with local memory, an internal clock, and a suite of communication equipment capable of both local line-of-sight communications and global broadcast communications. Some cells, denoted specialist cells, could contain such additional hardware as sensors and emitters. Each cell would be independent in the sense that there would be no global clock, no global (shared) memory, no pre-assigned cell identifiers, no pre-defined network topology, and no centralized brain or control structure. Like each cell in a living organism, each agent or cell of the computing system would contain a full description of the system encoded as genes, but in this case, the genes would be components of a software genome.

  4. Lesion progression in post-treatment persistent endodontic lesions.

    Science.gov (United States)

    Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

    2012-10-01

    Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Persisting nutritional neuropathy amongst former war prisoners.

    OpenAIRE

    Gill, G V; Bell, D R

    1982-01-01

    Of 898 former Far East prisoners of war, assessed between 1968 and 1981, 49 (5.5%) had evidence of persisting symptomatic neurological disease dating back to their periods of malnutrition in captivity. The commonest syndromes were peripheral neuropathy (often of "burning foot" type), optic atrophy, and sensori-neural deafness. Though nutritional neuropathies disappeared soon after release in most ex-Far East prisoners of war, in some they have persisted up to 36 years since exposure to the nu...

  6. Persistence of Overseeded Cool-Season Grasses in Bermudagrass Turf

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    Thomas Serensits

    2011-01-01

    Full Text Available Cool-season grass species are commonly overseeded into bermudagrass turf for winter color. When the overseeded grass persists beyond the spring; however, it becomes a weed. The ability of perennial ryegrass, Italian (annual ryegrass, intermediate ryegrass, and hybrid bluegrass to persist in bermudagrass one year after seeding was determined. Perennial ryegrass, intermediate ryegrass, and Italian ryegrass produced acceptable ground cover in the spring after fall seeding. Hybrid bluegrass did not establish well, resulting in unacceptable cover. Perennial ryegrass generally persisted the most one year after seeding, either because of summer survival of plants or because of new germination the following fall. Plant counts one year after seeding were greater in the higher seeding rate treatment compared to the lower seeding treatment rate of perennial ryegrass, suggesting new germination had occurred. Plant counts one year after seeding plots with intermediate ryegrass or Italian ryegrass were attributed primarily to latent germination and not summer survival. Applications of foramsulfuron generally did not prevent overseeded species stand one year after seeding, supporting the conclusion of new germination. Although quality is less with intermediate ryegrass compared to perennial ryegrass, it transitions out easier than perennial ryegrass, resulting in fewer surviving plants one year later.

  7. Low volumetric BMD is linked to upper-limb fracture in pubertal girls and persists into adulthood: a seven-year cohort study.

    Science.gov (United States)

    Cheng, Sulin; Xu, Leiting; Nicholson, Patrick H F; Tylavsky, Frances; Lyytikäinen, Arja; Wang, Qingju; Suominen, Harri; Kujala, Urho M; Kröger, Heikki; Alen, Markku

    2009-09-01

    The aetiology of increased incidence of fracture during puberty is unclear. This study aimed to determine whether low volumetric bone mineral density (vBMD) in the distal radius is associated with upper-limb fractures in growing girls, and whether any such vBMD deficit persists into adulthood. Fracture history from birth to 20 years was obtained and verified by medical records in 1034 Finnish girls aged 10-13 years. Bone density and geometry at distal radius, biomarkers and lifestyle/behavioural factors were assessed in a subset of 396 girls with a 7.5-year follow-up. We found that fracture incidence peaked during puberty (relative risk 3.1 at age of 8-14 years compared to outside this age window), and 38% of fractures were in the upper-limb. Compared to the non-fracture cohort, girls who sustained upper-limb fracture at ages 8-14 years had lower distal radial vBMD at baseline (258.9+/-37.5 vs. 287.5+/-34.1 mg/cm(3), p=0.001), 1-year (252.0+/-29.3 vs. 282.6+/-33.5 mg/cm(3), p=0.001), 2-year (258.9+/-32.2 vs. 289.9+/-40.1 mg/cm(3), p=0.003), and 7-year follow-ups (early adulthood, 307.6+/-35.9 vs. 343.6+/-40.9 mg/cm(3), p=0.002). There was a consistent trend towards larger bone cross-sectional area in the fracture cohort compared to non-fracture. In a logistic regression model, lower vBMD (p=0.001) was the only significant predictor of upper-limb fracture during the period of 8-14 years. Our results indicate that low BMD is an important factor underlying elevated upper-limb fracture risk during puberty, and that low BMD in pubertal girls with fracture persists into adulthood. Hence low vBMD during childhood is not a transient deficit. Methods to monitor vBMD and to maximise bone mineral accrual and reduce risks of falling in childhood should be developed.

  8. The fusion protein of wild-type canine distemper virus is a major determinant of persistent infection

    International Nuclear Information System (INIS)

    Plattet, Philippe; Rivals, Jean-Paul; Zuber, BenoIt; Brunner, Jean-Marc; Zurbriggen, Andreas; Wittek, Riccardo

    2005-01-01

    The wild-type A75/17 canine distemper virus (CDV) strain induces a persistent infection in the central nervous system but infects cell lines very inefficiently. In contrast, the genetically more distant Onderstepoort CDV vaccine strain (OP-CDV) induces extensive syncytia formation. Here, we investigated the roles of wild-type fusion (F WT ) and attachment (H WT ) proteins in Vero cells expressing, or not, the canine SLAM receptor by transfection experiments and by studying recombinants viruses expressing different combinations of wild-type and OP-CDV glycoproteins. We show that low fusogenicity is not due to a defect of the envelope proteins to reach the cell surface and that H WT determines persistent infection in a receptor-dependent manner, emphasizing the role of SLAM as a potent enhancer of fusogenicity. However, importantly, F WT reduced cell-to-cell fusion independently of the cell surface receptor, thus demonstrating that the fusion protein of the neurovirulent A75/17-CDV strain plays a key role in determining persistent infection

  9. NH125 kills methicillin-resistant Staphylococcus aureus persisters by lipid bilayer disruption.

    Science.gov (United States)

    Kim, Wooseong; Fricke, Nico; Conery, Annie L; Fuchs, Beth Burgwyn; Rajamuthiah, Rajmohan; Jayamani, Elamparithi; Vlahovska, Petia M; Ausubel, Frederick M; Mylonakis, Eleftherios

    2016-01-01

    NH125, a known WalK inhibitor kills MRSA persisters. However, its precise mode of action is still unknown. The mode of action of NH125 was investigated by comparing its spectrum of antimicrobial activity and its effects on membrane permeability and giant unilamellar vesicles (GUVs) with walrycin B, a WalR inhibitor and benzyldimethylhexadecylammonium chloride (16-BAC), a cationic surfactant. NH125 killed persister cells of a variety of Staphylococcus aureus strains. Similar to 16-BAC, NH125 killed MRSA persisters by inducing rapid membrane permeabilization and caused the rupture of GUVs, whereas walrycin B did not kill MRSA persisters or induce membrane permeabilization and did not affect GUVs. NH125 kills MRSA persisters by interacting with and disrupting membranes in a detergent-like manner.

  10. Occurrence and persistence of magnetic elements in the quiet Sun

    Science.gov (United States)

    Giannattasio, F.; Berrilli, F.; Consolini, G.; Del Moro, D.; Gošić, M.; Bellot Rubio, L.

    2018-03-01

    Context. Turbulent convection efficiently transports energy up to the solar photosphere, but its multi-scale nature and dynamic properties are still not fully understood. Several works in the literature have investigated the emergence of patterns of convective and magnetic nature in the quiet Sun at spatial and temporal scales from granular to global. Aims: To shed light on the scales of organisation at which turbulent convection operates, and its relationship with the magnetic flux therein, we studied characteristic spatial and temporal scales of magnetic features in the quiet Sun. Methods: Thanks to an unprecedented data set entirely enclosing a supergranule, occurrence and persistence analysis of magnetogram time series were used to detect spatial and long-lived temporal correlations in the quiet Sun and to investigate their nature. Results: A relation between occurrence and persistence representative for the quiet Sun was found. In particular, highly recurrent and persistent patterns were detected especially in the boundary of the supergranular cell. These are due to moving magnetic elements undergoing motion that behaves like a random walk together with longer decorrelations ( 2 h) with respect to regions inside the supergranule. In the vertices of the supegranular cell the maximum observed occurrence is not associated with the maximum persistence, suggesting that there are different dynamic regimes affecting the magnetic elements.

  11. Pluripotent stem cells: the last 10 years.

    Science.gov (United States)

    Kimbrel, Erin A; Lanza, Robert

    2016-12-01

    Pluripotent stem cells (PSCs) can differentiate into virtually any cell type in the body, making them attractive for both regenerative medicine and drug discovery. Over the past 10 years, technological advances and innovative platforms have yielded first-in-man PSC-based clinical trials and opened up new approaches for disease modeling and drug development. Induced PSCs have become the foremost alternative to embryonic stem cells and accelerated the development of disease-in-a-dish models. Over the years and with each new discovery, PSCs have proven to be extremely versatile. This review article highlights key advancements in PSC research, from 2006 to 2016, and how they will guide the direction of the field over the next decade.

  12. EBV induces persistent NF-κB activation and contributes to survival of EBV-positive neoplastic T- or NK-cells.

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    Honami Takada

    Full Text Available Epstein-Barr virus (EBV has been detected in several T- and NK-cell neoplasms such as extranodal NK/T-cell lymphoma nasal type, aggressive NK-cell leukemia, EBV-positive peripheral T-cell lymphoma, systemic EBV-positive T-cell lymphoma of childhood, and chronic active EBV infection (CAEBV. However, how this virus contributes to lymphomagenesis in T or NK cells remains largely unknown. Here, we examined NF-κB activation in EBV-positive T or NK cell lines, SNT8, SNT15, SNT16, SNK6, and primary EBV-positive and clonally proliferating T/NK cells obtained from the peripheral blood of patients with CAEBV. Western blotting, electrophoretic mobility shift assays, and immunofluorescent staining revealed persistent NF-κB activation in EBV-infected cell lines and primary cells from patients. Furthermore, we investigated the role of EBV in infected T cells. We performed an in vitro infection assay using MOLT4 cells infected with EBV. The infection directly induced NF-κB activation, promoted survival, and inhibited etoposide-induced apoptosis in MOLT4 cells. The luciferase assay suggested that LMP1 mediated NF-κB activation in MOLT4 cells. IMD-0354, a specific inhibitor of NF-κB that suppresses NF-κB activation in cell lines, inhibited cell survival and induced apoptosis. These results indicate that EBV induces NF-κB-mediated survival signals in T and NK cells, and therefore, may contribute to the lymphomagenesis of these cells.

  13. Chronic hepatitis caused by persistent parvovirus B19 infection

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    Mogensen Trine H

    2010-08-01

    Full Text Available Abstract Background Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions. Case Presentation Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection. Conclusions In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual

  14. Exoproteome analysis reveals higher abundance of proteins linked to alkaline stress in persistent Listeria monocytogenes strains.

    Science.gov (United States)

    Rychli, Kathrin; Grunert, Tom; Ciolacu, Luminita; Zaiser, Andreas; Razzazi-Fazeli, Ebrahim; Schmitz-Esser, Stephan; Ehling-Schulz, Monika; Wagner, Martin

    2016-02-02

    The foodborne pathogen Listeria monocytogenes, responsible for listeriosis a rare but severe infection disease, can survive in the food processing environment for month or even years. So-called persistent L. monocytogenes strains greatly increase the risk of (re)contamination of food products, and are therefore a great challenge for food safety. However, our understanding of the mechanism underlying persistence is still fragmented. In this study we compared the exoproteome of three persistent strains with the reference strain EGDe under mild stress conditions using 2D differential gel electrophoresis. Principal component analysis including all differentially abundant protein spots showed that the exoproteome of strain EGDe (sequence type (ST) 35) is distinct from that of the persistent strain R479a (ST8) and the two closely related ST121 strains 4423 and 6179. Phylogenetic analyses based on multilocus ST genes showed similar grouping of the strains. Comparing the exoproteome of strain EGDe and the three persistent strains resulted in identification of 22 differentially expressed protein spots corresponding to 16 proteins. Six proteins were significantly increased in the persistent L. monocytogenes exoproteomes, among them proteins involved in alkaline stress response (e.g. the membrane anchored lipoprotein Lmo2637 and the NADPH dehydrogenase NamA). In parallel the persistent strains showed increased survival under alkaline stress, which is often provided during cleaning and disinfection in the food processing environments. In addition, gene expression of the proteins linked to stress response (Lmo2637, NamA, Fhs and QoxA) was higher in the persistent strain not only at 37 °C but also at 10 °C. Invasion efficiency of EGDe was higher in intestinal epithelial Caco2 and macrophage-like THP1 cells compared to the persistent strains. Concurrently we found higher expression of proteins involved in virulence in EGDe e.g. the actin-assembly-inducing protein ActA and the

  15. Autologous Blood Pleurodesis In Patients With Persistent Air Leaks

    Directory of Open Access Journals (Sweden)

    Agkajanzadeh M

    2003-10-01

    Full Text Available Persistent air leaks occur after Spontaneous pneumothorax both primary and secondary, and after lungs trauma and lung surgeries are sever problems encountered chest surgeons with. Persistent air leak causes longer patients hospitalization."nMaterials and Methods: We used autologous blood pleurodesis in patients with persistent air leak for 30patients with more than 8 days air leaks, during a three years period 1377-1380 (1999-2002."nResults: The patients had 19 years up to 70 years old. Eight patients had thoracotomy and lobectomy and /or segmentectomies 6 with primary pneumothorax, 10 with secondary pneumothorax, and four with penetrated or blunt thoracic traumas. Blood was obtained from femoral or brachial veins and 70-150 mis. Injected in chest tubes. Chest bottle was first lied 80cm higher than body levels. After 24 hours repositioned in normal levels, and patients were supervised. Via chest tube we injected blood 70-100ml.for young patients, and 100-150 ml for older patients into intra pleural space. There were no clamped chest tubes. There were no pain, respiratory distress, fever, or cough in pleurodesized patients. The only patient's complaint was local pain in femoral vein or brachial vein because blood sampling and blood obtaining, although there was no local visible complication as hematoma or bleeding. After 48 hours in 24 patients air leak ceased. In six patients because persistent air leak autologous blood pleurodesis repeated, two patients after 48hours"nair leak ceased, remaining four patients underwent for thoracotomies, success rate"nwas 86.6%."nConclusion: According above success rate we suggest autologous blood pleurodesis in patients with persistent air leak is a reliable, effective, and no complicated procedure for persistent air leaks.

  16. Higher persistence with valsartan compared with enalapril in daily practice

    Directory of Open Access Journals (Sweden)

    Satu J Siiskonen

    2008-01-01

    Full Text Available Satu J Siiskonen1, Nancy S Breekveldt-Postma1, Gábor Vincze2, Zeba M Khan3, Joëlle A Erkens1, Ron MC Herings11PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAObjective: To compare persistence with valsartan and enalapril in daily practice.Methods: The PHARMO Record Linkage System includes various data registries including drug dispensing and hospitalizations for ≥2 million subjects in the Netherlands. Patients newly treated with valsartan or enalapril in the period of 1999–2002 were selected. Persistence was calculated by summing up the number of days of continuous treatment. Patients who remained on therapy with valsartan or enalapril for 12 or 24 months were defined as persistent at 1 or 2 years, respectively.Results: 3364 patients received valsartan and 9103 patients received enalapril. About 62% of patients treated with valsartan and 55% of patients treated with enalapril remained on therapy at 12 months after the initial dispensing, while 48% of patients treated with valsartan and 43% of patients treated with enalapril were persistent at 24 months. Patients treated with valsartan were about 20% more likely to stay on treatment than patients treated with enalapril (1 year RRadj: 1.23, 95% CI: 1.16–1.32; 2 years RRadj: 1.16, 95% CI: 1.11–1.23.Conclusions: Real-life persistence is higher with valsartan than with enalapril. The results of this and other studies on persistence in daily practice should be taken into account when deciding upon drug treatment for hypertension.Keywords: persistence, antihypertensive, valsartan, enalapril, angiotensin-converting enzyme inhibitors, angiotensin-2-receptor blockers

  17. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.

    Science.gov (United States)

    Cruz, Conrad Russell Y; Micklethwaite, Kenneth P; Savoldo, Barbara; Ramos, Carlos A; Lam, Sharon; Ku, Stephanie; Diouf, Oumar; Liu, Enli; Barrett, A John; Ito, Sawa; Shpall, Elizabeth J; Krance, Robert A; Kamble, Rammurti T; Carrum, George; Hosing, Chitra M; Gee, Adrian P; Mei, Zhuyong; Grilley, Bambi J; Heslop, Helen E; Rooney, Cliona M; Brenner, Malcolm K; Bollard, Catherine M; Dotti, Gianpietro

    2013-10-24

    Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.

  18. Persistent hyperparathyroidism is a major risk factor for fractures in the five years after kidney transplantation.

    Science.gov (United States)

    Perrin, P; Caillard, S; Javier, R M; Braun, L; Heibel, F; Borni-Duval, C; Muller, C; Olagne, J; Moulin, B

    2013-10-01

    The risk of fractures after kidney transplantation is high. Hyperparathyroidism frequently persists after successful kidney transplantation and contributes to bone loss, but its impact on fracture has not been demonstrated. This longitudinal study was designed to evaluate hyperparathyroidism and its associations with mineral disorders and fractures in the 5 posttransplant years. We retrospectively analyzed 143 consecutive patients who underwent kidney transplantation between August 2004 and April 2006. The biochemical parameters were determined at transplantation and at 3, 12 and 60 months posttransplantation, and fractures were recorded. The median intact parathyroid hormone (PTH) level was 334 ng/L (interquartile 151-642) at the time of transplantation and 123 ng/L (interquartile 75-224) at 3 months. Thirty fractures occurred in 22 patients. The receiver operating characteristic (ROC) curve analysis for PTH at 3 months (area under the ROC curve = 0.711, p = 0.002) showed that a good threshold for predicting fractures was 130 ng/L (sensitivity = 81%, specificity = 57%). In a multivariable analysis, independent risk factors for fracture were PTH >130 ng/L at 3 months (adjusted hazard ratio [AHR] = 7.5, 95% CI 2.18-25.50), and pretransplant osteopenia (AHR = 2.7, 95% CI 1.07-7.26). In summary, this study demonstrates for the first time that persistent hyperparathyroidism is an independent risk factor for fractures after kidney transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Quantifying the degree of persistence in random amoeboid motion based on the Hurst exponent of fractional Brownian motion.

    Science.gov (United States)

    Makarava, Natallia; Menz, Stephan; Theves, Matthias; Huisinga, Wilhelm; Beta, Carsten; Holschneider, Matthias

    2014-10-01

    Amoebae explore their environment in a random way, unless external cues like, e.g., nutrients, bias their motion. Even in the absence of cues, however, experimental cell tracks show some degree of persistence. In this paper, we analyzed individual cell tracks in the framework of a linear mixed effects model, where each track is modeled by a fractional Brownian motion, i.e., a Gaussian process exhibiting a long-term correlation structure superposed on a linear trend. The degree of persistence was quantified by the Hurst exponent of fractional Brownian motion. Our analysis of experimental cell tracks of the amoeba Dictyostelium discoideum showed a persistent movement for the majority of tracks. Employing a sliding window approach, we estimated the variations of the Hurst exponent over time, which allowed us to identify points in time, where the correlation structure was distorted ("outliers"). Coarse graining of track data via down-sampling allowed us to identify the dependence of persistence on the spatial scale. While one would expect the (mode of the) Hurst exponent to be constant on different temporal scales due to the self-similarity property of fractional Brownian motion, we observed a trend towards stronger persistence for the down-sampled cell tracks indicating stronger persistence on larger time scales.

  20. Persisting nutritional neuropathy amongst former war prisoners.

    Science.gov (United States)

    Gill, G V; Bell, D R

    1982-01-01

    Of 898 former Far East prisoners of war, assessed between 1968 and 1981, 49 (5.5%) had evidence of persisting symptomatic neurological disease dating back to their periods of malnutrition in captivity. The commonest syndromes were peripheral neuropathy (often of "burning foot" type), optic atrophy, and sensori-neural deafness. Though nutritional neuropathies disappeared soon after release in most ex-Far East prisoners of war, in some they have persisted up to 36 years since exposure to the nutritional insult. PMID:6292369

  1. Coral reef fish populations can persist without immigration

    KAUST Repository

    Salles, Océane C.

    2015-11-18

    Determining the conditions under which populations may persist requires accurate estimates of demographic parameters, including immigration, local reproductive success, and mortality rates. In marine populations, empirical estimates of these parameters are rare, due at least in part to the pelagic dispersal stage common to most marine organisms. Here, we evaluate population persistence and turnover for a population of orange clownfish, Amphiprion percula, at Kimbe Island in Papua New Guinea. All fish in the population were sampled and genotyped on five occasions at 2-year intervals spanning eight years. The genetic data enabled estimates of reproductive success retained in the same population (reproductive success to self-recruitment), reproductive success exported to other subpopulations (reproductive success to local connectivity), and immigration and mortality rates of sub-adults and adults. Approximately 50% of the recruits were assigned to parents from the Kimbe Island population and this was stable through the sampling period. Stability in the proportion of local and immigrant settlers is likely due to: low annual mortality rates and stable egg production rates, and the short larval stages and sensory capacities of reef fish larvae. Biannual mortality rates ranged from 0.09 to 0.55 and varied significantly spatially. We used these data to parametrize a model that estimated the probability of the Kimbe Island population persisting in the absence of immigration. The Kimbe Island population was found to persist without significant immigration. Model results suggest the island population persists because the largest of the subpopulations are maintained due to having low mortality and high self-recruitment rates. Our results enable managers to appropriately target and scale actions to maximize persistence likelihood as disturbance frequencies increase.

  2. Neural processes underlying cultural differences in cognitive persistence.

    Science.gov (United States)

    Telzer, Eva H; Qu, Yang; Lin, Lynda C

    2017-08-01

    Self-improvement motivation, which occurs when individuals seek to improve upon their competence by gaining new knowledge and improving upon their skills, is critical for cognitive, social, and educational adjustment. While many studies have delineated the neural mechanisms supporting extrinsic motivation induced by monetary rewards, less work has examined the neural processes that support intrinsically motivated behaviors, such as self-improvement motivation. Because cultural groups traditionally vary in terms of their self-improvement motivation, we examined cultural differences in the behavioral and neural processes underlying motivated behaviors during cognitive persistence in the absence of extrinsic rewards. In Study 1, 71 American (47 females, M=19.68 years) and 68 Chinese (38 females, M=19.37 years) students completed a behavioral cognitive control task that required cognitive persistence across time. In Study 2, 14 American and 15 Chinese students completed the same cognitive persistence task during an fMRI scan. Across both studies, American students showed significant declines in cognitive performance across time, whereas Chinese participants demonstrated effective cognitive persistence. These behavioral effects were explained by cultural differences in self-improvement motivation and paralleled by increasing activation and functional coupling between the inferior frontal gyrus (IFG) and ventral striatum (VS) across the task among Chinese participants, neural activation and coupling that remained low in American participants. These findings suggest a potential neural mechanism by which the VS and IFG work in concert to promote cognitive persistence in the absence of extrinsic rewards. Thus, frontostriatal circuitry may be a neurobiological signal representing intrinsic motivation for self-improvement that serves an adaptive function, increasing Chinese students' motivation to engage in cognitive persistence. Copyright © 2017 Elsevier Inc. All rights

  3. Nutrient transitions are a source of persisters in Escherichia coli biofilms.

    Directory of Open Access Journals (Sweden)

    Stephanie M Amato

    Full Text Available Chronic and recurrent infections have been attributed to persisters in biofilms, and despite this importance, the mechanisms of persister formation in biofilms remain unclear. The plethora of biofilm characteristics that could give rise to persisters, including slower growth, quorum signaling, oxidative stress, and nutrient heterogeneity, have complicated efforts to delineate formation pathways that generate persisters during biofilm development. Here we sought to specifically determine whether nutrient transitions, which are a common metabolic stress encountered within surface-attached communities, stimulate persister formation in biofilms and if so, to then identify the pathway. To accomplish this, we established an experimental methodology where nutrient availability to biofilm cells could be controlled exogenously, and then used that method to discover that diauxic carbon source transitions stimulated persister formation in Escherichia coli biofilms. Previously, we found that carbon source transitions stimulate persister formation in planktonic E. coli cultures, through a pathway that involved ppGpp and nucleoid-associated proteins, and therefore, tested the functionality of that pathway in biofilms. Biofilm persister formation was also found to be dependent on ppGpp and nucleoid-associated proteins, but the importance of specific proteins and enzymes between biofilm and planktonic lifestyles was significantly different. Data presented here support the increasingly appreciated role of ppGpp as a central mediator of bacterial persistence and demonstrate that nutrient transitions can be a source of persisters in biofilms.

  4. Nutrient transitions are a source of persisters in Escherichia coli biofilms.

    Science.gov (United States)

    Amato, Stephanie M; Brynildsen, Mark P

    2014-01-01

    Chronic and recurrent infections have been attributed to persisters in biofilms, and despite this importance, the mechanisms of persister formation in biofilms remain unclear. The plethora of biofilm characteristics that could give rise to persisters, including slower growth, quorum signaling, oxidative stress, and nutrient heterogeneity, have complicated efforts to delineate formation pathways that generate persisters during biofilm development. Here we sought to specifically determine whether nutrient transitions, which are a common metabolic stress encountered within surface-attached communities, stimulate persister formation in biofilms and if so, to then identify the pathway. To accomplish this, we established an experimental methodology where nutrient availability to biofilm cells could be controlled exogenously, and then used that method to discover that diauxic carbon source transitions stimulated persister formation in Escherichia coli biofilms. Previously, we found that carbon source transitions stimulate persister formation in planktonic E. coli cultures, through a pathway that involved ppGpp and nucleoid-associated proteins, and therefore, tested the functionality of that pathway in biofilms. Biofilm persister formation was also found to be dependent on ppGpp and nucleoid-associated proteins, but the importance of specific proteins and enzymes between biofilm and planktonic lifestyles was significantly different. Data presented here support the increasingly appreciated role of ppGpp as a central mediator of bacterial persistence and demonstrate that nutrient transitions can be a source of persisters in biofilms.

  5. Merkel cell polyomavirus infection and Merkel cell carcinoma.

    Science.gov (United States)

    Liu, Wei; MacDonald, Margo; You, Jianxin

    2016-10-01

    Merkel cell polyomavirus is the only polyomavirus discovered to date that is associated with a human cancer. MCPyV infection is highly prevalent in the general population. Nearly all healthy adults asymptomatically shed MCPyV from their skin. However, in elderly and immunosuppressed individuals, the infection can lead to a lethal form of skin cancer, Merkel cell carcinoma. In the last few years, new findings have established links between MCPyV infection, host immune response, and Merkel cell carcinoma development. This review discusses these recent discoveries on how MCPyV interacts with host cells to achieve persistent infection and, in the immunocompromised population, contributes to MCC development. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Melipona quadrifasciata (Hymenoptera: Apidae) fat body persists through metamorphosis with a few apoptotic cells and an increased autophagy.

    Science.gov (United States)

    Santos, Douglas Elias; Azevedo, Dihego Oliveira; Campos, Lúcio Antônio Oliveira; Zanuncio, José Cola; Serrão, José Eduardo

    2015-03-01

    Fat body, typically comprising trophocytes, provides energy during metamorphosis. The fat body can be renewed once the larval phase is complete or recycled and relocated to form the fat body of the adult insect. This study aims to identify the class of programmed cell death that occurs within the fat body cells during the metamorphosis of the stingless bee Melipona quadrifasciata. Using immunodetection techniques, the fat body of the post-defecating larvae and the white-, pink-, brown-, and black-eyed pupae were tested for cleaved caspase-3 and DNA integrity, followed by ultrastructural analysis and identification of autophagy using RT-PCR for the Atg1 gene. The fat body of M. quadrifasciata showed some apoptotic cells positive for cleaved caspase-3, although without DNA fragmentation. During development, the fat body cells revealed an increased number of mitochondria and free ribosomes, in addition to higher amounts of autophagy Atg1 mRNA, than that of the pupae. The fat body of M. quadrifasciata showed few cells which underwent apoptosis, but there was evidence of increased autophagy at the completion of the larval stage. All together, these data show that some fat body cells persist during metamorphosis in the stingless bee M. quadrifasciata.

  7. Long-term persistence with injectable therapy in relapsing-remitting multiple sclerosis: an 18-year observational cohort study.

    Directory of Open Access Journals (Sweden)

    Simon Zhornitsky

    Full Text Available Disease modifying therapies (DMTs reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS. Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA or interferon-β 1a/1b (IFN-β between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2% were lost to follow-up and 160 (11% moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54% started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

  8. Sputum Neutrophilia in Severe Persistent Asthmatics

    International Nuclear Information System (INIS)

    Naseem, A.; Zaidi, S. B. H.; Liaqat, J.; Iftikhar, R.

    2014-01-01

    Objective: To determine the frequency of sputum neutrophilia in patients with severe persistent bronchial asthma. Study Design: A cross-sectional study. Place and Duration of Study: Department of Medicine, Military Hospital, Rawalpindi, from November 2009 to November 2010. Methodology: Cases of severe persistent bronchial asthma, aged between 12 and 40 years, were included. Sputum samples were collected by induction with hypertonic saline (4.5%). All samples were centrifuged and differential neutrophil count was calculated. Data was analyzed using SPSS 11. Results: Out of 195 patients, there were 129 (66.2%) males and 66 (33.8%) females. The mean age was 27.01 A +- 6.92 years. Mean sputum neutrophilic count was 126.47 A +- 16.52 x 106/ml and the mean neutrophilic percentage was 63.187 A +- 8.3363. Sputum neutrophilia was present in 84 patients (43.1%), out of whom, 56 were males and 28 females. In patients with sputum neutrophilia, mean neutrophilic count was 142.40 A +- 8.49 x 106/ml and the mean neutrophilic percentage was 71.2024 A +- 4.2441%. Conclusion: Sputum neutrophilia is a frequent finding in cases with severe persistent bronchial asthma. Presence of sputum neutrophilia in such cases can lessen the inappropriate use of corticosteroids with their associated long-term side effects. (author)

  9. Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.

    Science.gov (United States)

    Cotugno, Nicola; De Armas, Lesley; Pallikkuth, Suresh; Rinaldi, Stefano; Issac, Biju; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-01-01

    Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27 + CD21 - ) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27 + CD21 + ) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses ( APRIL, BTK, BLIMP1 ) and

  10. Is Farm Management Skill Persistent?

    OpenAIRE

    Li, Xin; Paulson, Nicholas

    2014-01-01

    Farm management skills can affect farm managers' performance. In this article, farm management performance is analyzed based on yearly Illinois Farm Business Farm Management (FBFM) panel data across 6,760 farms from 1996 through 2011. Two out-of-sample measures of skill are used to analyze the ability of farm managers that consistently perform well over yearly and longer time horizons. Persistence tests show management skills are consistent and predictable. Results also suggest that the most ...

  11. Persistence of the prognostic importance of left ventricular systolic function and heart failure after myocardial infarction: 17-year follow-up of the TRACE register.

    Science.gov (United States)

    Kümler, Thomas; Gislason, Gunnar Hilmar; Køber, Lars; Torp-Pedersen, Christian

    2010-08-01

    Left ventricular systolic function and presence of heart failure (HF) are important prognostic factors and dictate future therapeutic strategies after myocardial infarction (MI). We evaluated persistence of the prognostic importance of left ventricular dysfunction and HF in consecutive MI patients screened for entry in the Trandolopril Cardiac Evaluation Registry (TRACE) study. The study population comprised 6676 MI patients screened for entry into the TRACE study, a double-blind, randomized, parallel group, placebo-controlled study of trandolapril vs. placebo in patients with left ventricular dysfunction after MI. In unadjusted analysis, patients with reduced left ventricular function and HF continued to show increased mortality. Landmark analysis and Cox proportional-hazards models showed that wall motion index (WMI) was a significant prognostic factor until 10 years of follow-up with hazard ratios ranging between 0.74 [confidence interval (CI) 0.71-0.78] and 0.90 (CI 0.82-0.98) associated with a 12% improvement in left ventricular ejection fraction (0.4 WMI units). The prognostic significance of HF persisted for 8 years with hazard ratios between 1.47 (CI 1.21-1.78) and 2.62 (95% CI 2.30-2.98) for the first 8 years. When assessed during the index MI, WMI and HF carry prognostic information for up to 10 years.

  12. Persistence of enteric viruses within oysters (Crassostrea virginica)

    Science.gov (United States)

    It is well known that water-borne enteric viruses are concentrated by bivalves. Why these viruses are selectively retained and remain infectious within shellfish tissues for extended periods is unknown. Our current hypothesis is that phagocytic hemocytes (blood cells) are a site of virus persiste...

  13. Self-Rated Health Trajectories among Married Americans: Do Disparities Persist over 20 Years?

    Directory of Open Access Journals (Sweden)

    Terceira A. Berdahl

    2018-01-01

    Full Text Available The purpose of this study is to understand self-rated health (SRH trajectories by social location (race/ethnicity by gender by social class among married individuals in the United States. We estimate multilevel models of SRH using six observations from 1980 to 2000 from a nationally representative panel of married individuals initially aged 25–55 (Marital Instability Over the Life Course Study. Results indicate that gender, race/ethnicity, and social class are associated with initial SRH disparities. Women are less healthy than men; people of color are less healthy than whites; lower educated individuals are less healthy than higher educated individuals. Women’s health declined slower than men’s but did not differ by race/ethnicity or education. Results from complex intersectional models show that white men with any college had the highest initial SRH. Only women with any college had significantly slower declines in SRH compared to white men with any college. For married individuals of all ages, most initial SRH disparities persist over twenty years. Intersecting statuses show that education provides uneven health benefits across racial/ethnic and gender subgroups.

  14. Phenotypes and functions of persistent Sendai virus-induced antibody forming cells and CD8+ T cells in diffuse nasal-associated lymphoid tissue typify lymphocyte responses of the gut.

    Science.gov (United States)

    Rudraraju, Rajeev; Surman, Sherri; Jones, Bart; Sealy, Robert; Woodland, David L; Hurwitz, Julia L

    2011-02-20

    Lymphocytes of the diffuse nasal-associated lymphoid tissue (d-NALT) are uniquely positioned to tackle respiratory pathogens at their point-of-entry, yet are rarely examined after intranasal (i.n.) vaccinations or infections. Here we evaluate an i.n. inoculation with Sendai virus (SeV) for elicitation of virus-specific antibody forming cells (AFCs) and CD8(+) T cells in the d-NALT. Virus-specific AFCs and CD8(+) T cells each appeared by day 7 after SeV inoculation and persisted for 8 months, explaining the long-sustained protection against respiratory virus challenge conferred by this vaccine. AFCs produced IgM, IgG1, IgG2a, IgG2b and IgA, while CD8+ T cells were cytolytic and produced low levels of cytokines. Phenotypic analyses of virus-specific T cells revealed striking similarities with pathogen-specific immune responses in the intestine, highlighting some key features of adaptive immunity at a mucosal site. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic Escherichia coli.

    Science.gov (United States)

    Molina-Quiroz, Roberto C; Silva-Valenzuela, Cecilia; Brewster, Jennifer; Castro-Nallar, Eduardo; Levy, Stuart B; Camilli, Andrew

    2018-01-09

    Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli , as measured by survival after exposure to a β-lactam antibiotic. This phenotype is regulated by a set of genes leading to an oxidative stress response and SOS-dependent DNA repair. Thus, persister cells tolerant to cell wall-acting antibiotics must cope with oxidative stress and DNA damage and these processes are regulated by cyclic AMP in uropathogenic E. coli IMPORTANCE Bacterial persister cells are important in relapsing infections in patients treated with antibiotics and also in the emergence of antibiotic resistance. Our results show that in uropathogenic E. coli , the second messenger cyclic AMP negatively regulates persister cell formation, since in its absence much more persister cells form that are tolerant to β-lactams antibiotics. We reveal the mechanism to be decreased levels of reactive oxygen species, specifically hydroxyl radicals, and SOS-dependent DNA repair. Our findings suggest that the oxidative stress response and DNA repair are relevant pathways to target in the design of persister-specific antibiotic compounds. Copyright © 2018 Molina-Quiroz et al.

  16. Persistence of Breakage in Specific Chromosome Bands 6 Years after Acute Exposure to Oil.

    Directory of Open Access Journals (Sweden)

    Alexandra Francés

    Full Text Available The identification of breakpoints involved in chromosomal damage could help to detect genes involved in genetic disorders, most notably cancer. Until now, only one published study, carried out by our group, has identified chromosome bands affected by exposure to oil from an oil spill. In that study, which was performed two years after the initial oil exposure in individuals who had participated in clean-up tasks following the wreck of the Prestige, three chromosomal bands (2q21, 3q27, 5q31 were found to be especially prone to breakage. A recent follow-up study, performed on the same individuals, revealed that the genotoxic damage had persisted six years after oil exposure.To determine whether there exist chromosome bands which are especially prone to breakages and to know if there is some correlation with those detected in the previous study. In addition, to investigate if the DNA repair problems detected previously persist in the present study.Follow-up study performed six years after the Prestige oil spill.Fishermen cooperatives in coastal villages.Fishermen highly exposed to oil spill who participated in previous genotoxic study six years after the oil.Chromosome damage in peripheral lymphocytes. For accurate identification of the breakpoints involved in chromosome damage of circulating lymphocytes, a sequential stain/G-banding technique was employed. To determine the most break-prone chromosome bands, two statistical methods, the Fragile Site Multinomial and the chi-square tests (where the bands were corrected by their length were used. To compare the chromosome lesions, structural chromosome alterations and gaps/breaks between two groups of individuals we used the GEE test which takes into account a possible within-individual correlation. Dysfunctions in DNA repair mechanisms, expressed as chromosome damage, were assessed in cultures with aphidicolin by the GEE test.Cytogenetic analyses were performed in 47 exposed individuals. A total of

  17. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer.

    Science.gov (United States)

    Priceman, Saul J; Gerdts, Ethan A; Tilakawardane, Dileshni; Kennewick, Kelly T; Murad, John P; Park, Anthony K; Jeang, Brook; Yamaguchi, Yukiko; Yang, Xin; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E; Wu, Anna M; Brown, Christine E; Forman, Stephen J

    2018-01-01

    Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies.

  18. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer

    Science.gov (United States)

    Priceman, Saul J.; Gerdts, Ethan A.; Tilakawardane, Dileshni; Kennewick, Kelly T.; Murad, John P.; Park, Anthony K.; Jeang, Brook; Yamaguchi, Yukiko; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E.; Brown, Christine E.; Forman, Stephen J.

    2018-01-01

    ABSTRACT Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. PMID:29308300

  19. Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome.

    Science.gov (United States)

    Rasmussen, Thomas A; McMahon, James; Chang, J Judy; Symons, Jori; Roche, Michael; Dantanarayana, Ashanti; Okoye, Afam; Hiener, Bonnie; Palmer, Sarah; Lee, Wen Shi; Kent, Stephen J; Van Der Weyden, Carrie; Prince, H Miles; Cameron, Paul U; Lewin, Sharon R

    2017-08-24

    To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4 T cells. Case report. Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR-VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in total CD4 T cells, in sorted malignant and nonmalignant CD4 T cells, was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing. HIV-hepatitis B virus coinfection was diagnosed and antiretroviral therapy initiated 4 years prior to presentation with Sezary syndrome and primary cutaneous anaplastic large cell lymphoma. The patient received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4 T cells, consistent with expansion of a noninfected CD4 T-cell clone. Full-length HIV-DNA sequencing demonstrated multiple defective viruses but no identical or expanded sequences. Alemtuzumab extensively depleted T cells, including more than 1 log reduction in total T cells and more than 3 log reduction in CD4 T cells. Finally, alemtuzumab decreased HIV-DNA in CD4 T cells by 57% but HIV-DNA remained detectable at low levels even after depletion of nearly all CD4 T cells. Alemtuzumab extensively depleted multiple T-cell subsets and decreased the frequency of but did not eliminate HIV-infected CD4 T cells. Studying the effects on HIV persistence following immune recovery in HIV-infected individuals who require alemtuzumab for malignancy or in animal studies may provide further insights into novel cure strategies.

  20. Hepatitis E virus persists in the presence of a type III interferon response.

    Science.gov (United States)

    Yin, Xin; Li, Xinlei; Ambardekar, Charuta; Hu, Zhimin; Lhomme, Sébastien; Feng, Zongdi

    2017-05-01

    The RIG-I-like RNA helicase (RLR)-mediated interferon (IFN) response plays a pivotal role in the hepatic antiviral immunity. The hepatitis A virus (HAV) and the hepatitis C virus (HCV) counter this response by encoding a viral protease that cleaves the mitochondria antiviral signaling protein (MAVS), a common signaling adaptor for RLRs. However, a third hepatotropic RNA virus, the hepatitis E virus (HEV), does not appear to encode a functional protease yet persists in infected cells. We investigated HEV-induced IFN responses in human hepatoma cells and primary human hepatocytes. HEV infection resulted in persistent virus replication despite poor spread. This was companied by a type III IFN response that upregulated multiple IFN-stimulated genes (ISGs), but type I IFNs were barely detected. Blocking type III IFN production or signaling resulted in reduced ISG expression and enhanced HEV replication. Unlike HAV and HCV, HEV did not cleave MAVS; MAVS protein size, mitochondrial localization, and function remained unaltered in HEV-replicating cells. Depletion of MAVS or MDA5, and to a less extent RIG-I, also diminished IFN production and increased HEV replication. Furthermore, persistent activation of the JAK/STAT signaling rendered infected cells refractory to exogenous IFN treatment, and depletion of MAVS or the receptor for type III IFNs restored the IFN responsiveness. Collectively, these results indicate that unlike other hepatotropic RNA viruses, HEV does not target MAVS and its persistence is associated with continuous production of type III IFNs.

  1. Daikenchuto ameliorates muscle hypercontractility in a murine T-cell-mediated persistent gut motor dysfunction model.

    Science.gov (United States)

    Akiho, Hirotada; Nakamura, Kazuhiko

    2011-01-01

    Low-grade inflammation and immunological alterations are evident in functional gastrointestinal disorders such as irritable bowel syndrome (IBS). We evaluated the effects of daikenchuto (DKT), a pharmaceutical grade Japanese herbal medicine, on the hypercontractility of intestinal smooth muscle persisting after acute inflammation induced by a T-cell-activating anti-CD3 antibody (αCD3). BALB/c mice were injected with αCD3 (12.5 μg, i.p.), and DKT (2.7 g/kg) was administered orally once daily for 1 week. The contraction of isolated small intestinal muscle strips and muscle cells was examined on day 7 after αCD3 injection. The gene and protein expressions in the small intestines were evaluated by real-time PCR and multiplex immunoassays, respectively, on days 1, 3 and 7 after αCD3 injection. αCD3 injection resulted in significant increases in carbachol-evoked contractility in the muscle strips and isolated smooth muscle cells on day 7. DKT ameliorated the αCD3-induced muscle hypercontractility on day 7 in both the muscle strips and smooth muscle cells. αCD3 injection rapidly up- and downregulated the mRNA and protein expressions of pro- and anti-inflammatory cytokines, respectively. Although the influence of DKT on the mRNA expressions was moderate, the protein expressions of IL-13 and IL-17 were significantly decreased. We observed changes in the intestinal muscle contractility in muscle strips and muscle cells following resolution of inflammation in a T-cell-mediated model of enteropathy. The observed modulation of cytokine expression and function by DKT may lead to the development of new pharmacotherapeutic strategies aimed at a wide variety of gut motor dysfunction disorders. Copyright © 2011 S. Karger AG, Basel.

  2. Hallucinogen persisting perception disorder after psilocybin consumption: a case study.

    Science.gov (United States)

    Espiard, Marie-Laure; Lecardeur, Laurent; Abadie, Pascale; Halbecq, Isabelle; Dollfus, Sonia

    2005-08-01

    The recurrence of flashbacks without acute or chronic hallucinogen consumption has been recognized in the DSM IV criteria as the hallucinogen persisting perception disorder (HPPD). Perceptual disturbances may last for 5 years or more and represent a real psychosocial distress. We reported here a case of a 18-year-old young man presenting HPPD after a mixed intoxication with psylocibin and cannabis. This report shows symptomatic recurrences persisting more than 8 months. Various differential diagnoses were evoked and our therapeutic strategies were described.

  3. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype.

    Directory of Open Access Journals (Sweden)

    Alvar Agustí

    Full Text Available Because chronic obstructive pulmonary disease (COPD is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552.Six inflammatory biomarkers in peripheral blood (white blood cells (WBC count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001 and exacerbation frequency (1.5 (1.5 vs. 0.9 (1.1 per year, p<0.001 compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.

  4. Long-term persistence of immunity and B-cell memory following Haemophilus influenzae type B conjugate vaccination in early childhood and response to booster.

    Science.gov (United States)

    Perrett, K P; John, T M; Jin, C; Kibwana, E; Yu, L-M; Curtis, N; Pollard, A J

    2014-04-01

    Protection against Haemophilus influenzae type b (Hib), a rapidly invading encapsulated bacteria, is dependent on maintenance of an adequate level of serum antibody through early childhood. In many countries, Hib vaccine booster doses have been implemented after infant immunization to sustain immunity. We investigated the long-term persistence of antibody and immunological memory in primary-school children following infant (with or without booster) Hib vaccination. Anti-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) concentration and the frequency of circulating Hib-specific memory B cells were measured before a booster of a Hib-serogroup C meningococcal (MenC) conjugate vaccine and again 1 week, 1 month, and 1 year after the booster in 250 healthy children aged 6-12 years in an open-label phase 4 clinical study. Six to 12 years following infant priming with 3 doses of Hib conjugate vaccine, anti-PRP IgG geometric mean concentrations were 3.11 µg/mL and 0.71 µg/mL and proportions with anti-PRP IgG ≥1.0 µg/mL were 79% and 43% in children who had or had not, respectively, received a fourth Hib conjugate vaccine dose (mean age, 3.9 years). Higher baseline and post-Hib-MenC booster responses (anti-PRP IgG and memory B cells) were found in younger children and in those who had received a fourth Hib dose. Sustained Hib conjugate vaccine-induced immunity in children is dependent on time since infant priming and receipt of a booster. Understanding the relationship between humoral and cellular immunity following immunization with conjugate vaccines may direct vaccine design and boosting strategies to sustain individual and population immunity against encapsulated bacteria in early childhood. Clinical Trials Registration ISRCTN728588998.

  5. The Economy of Persistence: Mario the Tailor

    Directory of Open Access Journals (Sweden)

    Prudence Black

    2016-03-01

    Full Text Available Mario Conte has had a tailor shop in King Street, Newtown since the mid 1960s. Taking an interview with Mario as its point of departure, this article describes the persistence of a skilled worker whose practices and techniques remain the same in a world that has long changed. While inattentive to what rules might be used to decorate a shop window, Mario continues to make and sew in the way that he learnt in post-war Italy. Mario’s persistence could be described as all the skills and other elements that need to be in place to keep him working, in particular the tradition of tailoring techniques he has remained true to over the last fifty years. The hand stitching of his tailoring is like a metronome of that persistence.

  6. Defining Persistent Hotspots: Areas That Fail to Decrease Meaningfully in Prevalence after Multiple Years of Mass Drug Administration with Praziquantel for Control of Schistosomiasis.

    Science.gov (United States)

    Kittur, Nupur; Binder, Sue; Campbell, Carl H; King, Charles H; Kinung'hi, Safari; Olsen, Annette; Magnussen, Pascal; Colley, Daniel G

    2017-12-01

    Preventive chemotherapy with praziquantel for schistosomiasis morbidity control is commonly done by mass drug administration (MDA). MDA regimen is usually based on prevalence in a given area, and effectiveness is evaluated by decreases in prevalence and/or intensity of infection after several years of implementation. Multiple studies and programs now find that even within well-implemented, multiyear, annual MDA programs there often remain locations that do not decline in prevalence and/or intensity to expected levels. We term such locations "persistent hotspots." To study and address persistent hotspots, investigators and neglected tropical disease (NTD) program managers need to define them based on changes in prevalence and/or intensity. But how should the data be analyzed to define a persistent hotspot? We have analyzed a dataset from an operational research study in western Tanzania after three annual MDAs using four different approaches to define persistent hotspots. The four approaches are 1) absolute percent change in prevalence; 2) percent change in prevalence; 3) change in World Health Organization guideline categories; 4) change (absolute or percent) in both prevalence and intensity. We compare and contrast the outcomes of these analyses. Our intent is to show how the same dataset yields different numbers of persistent hotspots depending on the approach used to define them. We suggest that investigators and NTD program managers use the approach most suited for their study or program, but whichever approach is used, it should be clearly stated so that comparisons can be made within and between studies and programs.

  7. Persistent discharges in dentate gyrus perisoma-inhibiting interneurons require hyperpolarization-activated cyclic nucleotide-gated channel activation.

    Science.gov (United States)

    Elgueta, Claudio; Köhler, Johannes; Bartos, Marlene

    2015-03-11

    Parvalbumin (PV)-expressing perisoma-inhibiting interneurons (PIIs) of the dentate gyrus integrate rapidly correlated synaptic inputs and generate short-duration action potentials that propagate along the axon to their output synapses, supporting fast inhibitory signaling onto their target cells. Here we show that PV-PIIs in rat and mouse dentate gyrus (DG) integrate their intrinsic activity over time and can turn into a persistent firing mode characterized by the ability to generate long-lasting trains of action potentials at ∼50 Hz in the absence of additional inputs. Persistent firing emerges in the axons remote from the axon initial segment and markedly depends on hyperpolarization-activated cyclic nucleotide-gated channel (HCNC) activation. Persistent firing properties are modulated by intracellular Ca(2+) levels and somatic membrane potential. Detailed computational single-cell PIIs models reveal that HCNC-mediated conductances can contribute to persistent firing during conditions of a shift in their voltage activation curve to more depolarized potentials. Paired recordings from PIIs and their target granule cells show that persistent firing supports strong inhibitory output signaling. Thus, persistent firing may emerge during conditions of intense activation of the network, thereby providing silencing to the circuitry and the maintenance of sparse activity in the dentate gyrus. Copyright © 2015 the authors 0270-6474/15/354131-09$15.00/0.

  8. Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients.

    Science.gov (United States)

    Balti, Eric V; Vandemeulebroucke, Evy; Weets, Ilse; Van De Velde, Ursule; Van Dalem, Annelien; Demeester, Simke; Verhaeghen, Katrijn; Gillard, Pieter; De Block, Christophe; Ruige, Johannes; Keymeulen, Bart; Pipeleers, Daniel G; Decochez, Katelijn; Gorus, Frans K

    2015-02-01

    In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D). The design is a registry-based study. Functional tests were performed in a hospital setting. Persistently autoAb(+) first-degree relatives of patients with T1D (n = 81; age 5-39 years). We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC(5-10 min); min 5-10) was determined in all relatives and second-phase release (AUC(120-150 min); min 120-150) in those aged 12-39 years (n = 62). Overall, the predictive ability of AUC(5-10 min) was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80-0.98] vs 0.81 [0.70-0.93]). Fasting blood glucose (FBG) and AUC(5-10 min) provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84-1.00]). In multivariate Cox regression analysis, AUC(5-10 min)) (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC(5-10 min) below percentile 10 of controls was associated with 50-70% progression to T1D regardless of age. Similar results were obtained for AUC(120-150 min). Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb(+) offspring and siblings of T1D patients to predict impending diabetes.

  9. A population-based study of dosing and persistence with anti-dementia medications.

    LENUS (Irish Health Repository)

    Brewer, Linda

    2013-02-27

    PURPOSE: Cholinesterase inhibitors and memantine are the mainstay of pharmacological intervention for the cognitive symptoms of Alzheimer\\'s disease (AD). This study assessed the adequacy of dosing and persistence with AD medications and the predictors of these variables in the \\'real world\\' (outside the clinical trial setting). METHODS: The Health Service Executive-Primary Care Reimbursement Services prescription claims database in the Republic of Ireland contains prescription information for 1.6 million people. Patients aged >70 years who received at least two prescriptions for donepezil, rivastigmine, galantamine and memantine between January 2006 and December 2010 were included in the study. Rates of dose-maximisation were recorded by examining the initiation dose of each AD drug commenced during the study period and any subsequent dose titrations. Non-persistence was defined by a gap in prescribing of more than 63 consecutive days. Predictors of dose-maximisation and non-persistence were also analysed. RESULTS: Between January 2006 and December 2010, 20,729 patients aged >70 years received a prescription for an AD medication. Despite most patients on donepezil and memantine receiving a prescription for the maximum drug dose, this dose was maintained for 2 consecutive months in only two-thirds of patients. Patients were significantly more likely to have their doses of donepezil and memantine maximised if prescribed in more recent years (2010 vs. 2007). Rates of non-persistence were 30.1 % at 6 months and 43.8 % at 12 months. Older age [75+ vs. <75 years; hazards ratio (HR) 1.16, 95 % confidence interval (CI) 1.06-1.27] and drug type (rivastigmine vs. donepezil; HR 1.15, 95 % CI 1.03-1.27) increased the risk of non-persistence. Non-persistence was lower for those commencing therapy in more recent years (2010 vs. 2007; HR 0.81, 95 % CI 0.73-0.89, p < 0.001) and for those on multiple anti-dementia medications (HR 0.59, 95 % CI 0

  10. Persistent pain is common 1 year after ankle and wrist fracture surgery: a register-based questionnaire study

    DEFF Research Database (Denmark)

    Friesgaard, Kristian Dahl; Gromov, Kirill; Knudsen, Lone

    2016-01-01

    BACKGROUND: Substantial literature documents that persistent postsurgical pain is a possible outcome of many common surgical procedures. As fracture-related surgery implies a risk of developing neuropathic pain and complex regional pain syndrome (CRPS), further studies investigating the prevalence...... and pain characteristics are required. METHODS: All patients undergoing primary surgery because of ankle or wrist fracture at Hvidovre and Odense University Hospitals, Denmark, between April 15, 2013 and April 15, 2014, were identified from the Danish Fracture Database. A questionnaire regarding pain...... be informed about the substantial risk of developing persistent postsurgical pain. Future studies investigating risk factors for persistent postsurgical pain that include both surgically and conservatively treated fractures are required....

  11. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    International Nuclear Information System (INIS)

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

    2015-01-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm

  12. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E., E-mail: claudia.ruebe@uks.eu

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  13. Distribution, persistence and interchange of Epstein-Barr virus strains among PBMC, plasma and saliva of primary infection subjects.

    Science.gov (United States)

    Kwok, Hin; Chan, Koon Wing; Chan, Kwok Hung; Chiang, Alan Kwok Shing

    2015-01-01

    Our study aimed at investigating the distribution, persistence and interchange of viral strains among peripheral blood mononuclear cells (PBMC), plasma and saliva of primary Epstein-Barr virus (EBV) infection subjects. Twelve infectious mononucleosis (IM) patients and eight asymptomatic individuals (AS) with primary EBV infection were followed longitudinally at several time points for one year from the time of diagnosis, when blood and saliva samples were collected and separated into PBMC, plasma and saliva, representing circulating B cell, plasma and epithelial cell compartments, respectively. To survey the viral strains, genotyping assays for the natural polymorphisms in two latent EBV genes, EBNA2 and LMP1, were performed and consisted of real-time PCR on EBNA2 to distinguish type 1 and 2 viruses, fluorescent-based 30-bp typing assay on LMP1 to distinguish deletion and wild type LMP1, and fluorescent-based heteroduplex tracking assays on both EBNA2 and LMP1 to distinguish defined polymorphic variants. No discernible differences were observed between IM patients and AS. Multiple viral strains were acquired early at the start of infection. Stable persistence of dominant EBV strains in the same tissue compartment was observed throughout the longitudinal samples. LMP1-defined strains, China 1, China 2 and Mediterranean+, were the most common strains observed. EBNA2-defined groups 1 and 3e predominated the PBMC and saliva compartments. Concordance of EBNA2 and LMP1 strains between PBMC and saliva suggested ready interchange of viruses between circulating B cell and epithelial cell pools, whilst discordance of viral strains observed between plasma and PBMC/saliva indicated presence of viral pools in other undetermined tissue compartments. Taken together, the results indicated that the distribution, persistence and interchange of viral strains among the tissue compartments are more complex than those proposed by the current model of EBV life cycle.

  14. Persistent 'hotspots' of lymphatic filariasis microfilaraemia despite 14 years of mass drug administration in Ghana.

    Science.gov (United States)

    Biritwum, Nana-Kwadwo; Yikpotey, Paul; Marfo, Benjamin K; Odoom, Samuel; Mensah, Ernest O; Asiedu, Odame; Alomatu, Bright; Hervie, Edward T; Yeboah, Abednego; Ade, Serge; Hinderaker, Sven G; Reid, Anthony; Takarinda, Kudakwashe C; Koudou, Benjamin; Koroma, Joseph B

    2016-12-01

    Among the 216 districts in Ghana, 98 were declared endemic for lymphatic filariasis in 1999 after mapping. Pursuing the goal of elimination, WHO recommends annual treatment using mass drugs administration (MDA) for at least 5 years. MDA was started in the country in 2001 and reached national coverage in 2006. By 2014, 69 districts had 'stopped-MDA' (after passing the transmission assessment survey) while 29 others remained with persistent microfilaraemia (mf) prevalence (≥1%) despite more than 11 years of MDA and were classified as 'hotspots'. An ecological study was carried out to compare baseline mf prevalence and anti-microfilaria interventions between hotspot and stopped-MDA districts. Baseline mf prevalence was significantly higher in hotspots than stopped-MDA districts (photspot districts, but it was still higher than in stopped-MDA districts. The number of MDA rounds was slightly higher in hotspot districts (photspots and stopped-MDA districts was a high baseline mf prevalence. This finding indicates that the recommended 5-6 rounds annual treatment may not achieve interruption of transmission. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

    Directory of Open Access Journals (Sweden)

    Sally N. Adebamowo

    2017-06-01

    Full Text Available BackgroundRecent studies have suggested that the vaginal microenvironment plays a role in persistence of high-risk human papillomavirus (hrHPV infection and thus cervical carcinogenesis. Furthermore, it has been shown that some mycoplasmas are efficient methylators and may facilitate carcinogenesis through methylation of hrHPV and cervical somatic cells. We examined associations between prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and prevalent as well as persistent hrHPV infections.MethodsWe examined 194 Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal microbiota established by sequencing the V3–V4 hypervariable regions of the 16S rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV based on positive result of baseline tests, while persistence was defined as positive results from two consecutive tests. We used exact logistic regression models to estimate associations between Mycoplasma spp. and hrHPV infections.ResultsThe mean (SD age of the study participants was 38 (8 years, 71% were HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV positive at baseline. At follow-up, 16% of the women remained positive for M. genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI 1.49–51.6, p 0.01. Women who were positive for HIV and had persistent M. hominis had threefold increase in the odds of having persistent hrHPV infection (OR 3.28, 95% CI 1.31–8.74, p 0.008, compared to women who were negative for both.ConclusionWe found significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but we could not rule out reverse causation. Our findings need to be replicated in larger, longitudinal studies and if confirmed

  16. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney.

    Directory of Open Access Journals (Sweden)

    Troy Camarata

    Full Text Available New nephron formation (nephrogenesis ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.

  17. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney.

    Science.gov (United States)

    Camarata, Troy; Howard, Alexis; Elsey, Ruth M; Raza, Sarah; O'Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

    2016-01-01

    New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.

  18. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney

    Science.gov (United States)

    Camarata, Troy; Howard, Alexis; Elsey, Ruth M.; Raza, Sarah; O’Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

    2016-01-01

    New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population. PMID:27144443

  19. Transposon mutagenesis identifies novel genes associated with Staphylococcus aureus persister formation

    Directory of Open Access Journals (Sweden)

    Wang ewenjie

    2015-12-01

    Full Text Available Pathogenic bacterial persisters are responsible for the recalcitrance of chronic and persistent infections to antimicrobial therapy. Although the mechanisms of persister formation and survival have been widely studied in Escherichia coli, persistence mechanisms in S. aureus remain largely unknown. Here, we screened a transposon mutant library of a clinical methicillin-resistant Staphylococcus aureus(MRSA)strain, USA500 (ST8, under antibiotic pressure and identified 13 genes whose insertion mutations resulted in a defect in persistence. These candidate genes were further confirmed by evaluating the survival of the mutants upon exposure to levofloxacin and several other stress conditions. We found 13 insertion mutants with significantly lower persister numbers under several stress conditions, including sdhA, sdhB, ureG, mnhG1, fbaA, ctaB, clpX, parE, HOU_0223, HOU_0587, HOU_2091, HOU_2315 and HOU_2346, which mapped into pathways of oxidative phosphorylation, TCA cycle, glycolysis, cell cycle and ABC transporters, suggesting that these genes and pathways may play an important role in persister formation and survival. The newly constructed knockout strains of ureG, sdhA and sdhB and their complemented strains were also tested for defect in persisters following exposure to levofloxacin and several other stress conditions. The results from these experiments were consistent with the screening results, which indicated that deletion of these genes in MRSA USA500 leads to persister defect. These findings provide novel insights into the mechanisms of persister formation and survival in S. aureus and offer new targets for the development of persister-directed antibiotics for the improved treatment of chronic and persistent infections.

  20. Patterns of persistence with pharmacological treatment among patients with current depressive episode and their impact on long-term outcome: a naturalistic study with 5-year follow-up

    Directory of Open Access Journals (Sweden)

    Li K

    2018-05-01

    Full Text Available Kanglai Li,1,* Jiong Tao,2,* Yuemei Li,3 Minhua Chen,2 Xiuhua Wu,2 Yingtao Liao,2 Xiaolan Lin,4 Zhaoyu Gan2 1Department of Very Important Patient, the 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Psychiatry, the 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Obstetrics, Wuzhou Gongren Hospital, Wuzhou, People’s Republic of China; 4Department of Infectious Diseases, the 3rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: The aim of the study was to describe and compare the patterns of medication persistence among patients with unipolar depression (UD or bipolar depression in a 5-year follow-up, and explore their impact on long-term outcome. Patients and methods: A total of 333 eligible patients with current major depressive episode were observed and followed up from the first index prescription for 5 years. Lack of persistence or treatment interruption was defined as a gap of at least 2 consecutive months without taking any medication. Time to lack of persistence in the first (TLP1 and the second (TLP2 episode of treatment, number of visits before the first treatment interruption (NV and number of treatment interruptions (NTI were measured. Results: During the 5-year follow-up, nearly 50% of patients experienced at least two times of treatment interruption. Pattern of medication persistence did not significantly differ between UD and bipolar disorder (BD patients. TLP1 was positively associated with TLP2. Shorter TLP1 predicted a higher possibility of subsequent visits because of recurrence or relapse and more NTI meant a lower likelihood of achieving full remission in the fifth year for both UD and BD patients. For UD patients, shorter TLP1 or less NV predicted a lower chance of achieving remission, while for BD patients

  1. Identifying Stem-like Cells Using Mitochondrial Membrane Potential | Center for Cancer Research

    Science.gov (United States)

    Therapies that are based on living cells promise to improve treatments for metastatic cancer and for many degenerative diseases. Lasting treatment of these maladies may require the durable persistence of cells. Long-term engraftment of cells – for months or years – and the generation of large numbers of progeny are characteristics of stem cells. Most approaches to isolate

  2. Persistence of urinary excretion products of benzo(a)pyrene

    International Nuclear Information System (INIS)

    Uziel, M.; Haglund, R.; White, D.A.

    1988-01-01

    Persistence of DNA-adducts has been observed in a variety of experimental circumstances and has been suggested as one potential mechanism for explaining the long-term delay before expression of proliferative disease. In this concept, a stable DNA-adduct, which is a remnant of a prior exposure in a nondividing cell, would not express the genotoxic effect until the cells were stimulated to divide, and thus explain the long-term delay in expression of cancer. An alternative view of the observation of persistent DNA-adducts, described in this communication, is the continuing replenishment of DNA adducts by formation and turnover of these adducts from exposure to a constant supply of the ultimate carcinogenic species derived from a prior exposure. It is of interest to note that virtually all experiments where ''persistent'' adducts have been observed have been high dose exposures. During the course of experiments designed to develop improved methods for detection of DNA adducts and related derivatives derived from polynuclear aromatic hydrocarbons (PAH), we observed that there was a continuous excretion of urinary derivatives of the injected benzo(a)pyrene (BaP) beyond the initial burst of detoxification. This report describes the time dependent distribution of those derivatives in blood, urine, feces, and at the site of injection. 11 refs., 5 figs., 4 tabs

  3. Clinical progress of human papillomavirus genotypes and their persistent infection in subjects with atypical squamous cells of undetermined significance cytology: Statistical and latent Dirichlet allocation analysis

    Science.gov (United States)

    Kim, Yee Suk; Lee, Sungin; Zong, Nansu; Kahng, Jimin

    2017-01-01

    The present study aimed to investigate differences in prognosis based on human papillomavirus (HPV) infection, persistent infection and genotype variations for patients exhibiting atypical squamous cells of undetermined significance (ASCUS) in their initial Papanicolaou (PAP) test results. A latent Dirichlet allocation (LDA)-based tool was developed that may offer a facilitated means of communication to be employed during patient-doctor consultations. The present study assessed 491 patients (139 HPV-positive and 352 HPV-negative cases) with a PAP test result of ASCUS with a follow-up period ≥2 years. Patients underwent PAP and HPV DNA chip tests between January 2006 and January 2009. The HPV-positive subjects were followed up with at least 2 instances of PAP and HPV DNA chip tests. The most common genotypes observed were HPV-16 (25.9%, 36/139), HPV-52 (14.4%, 20/139), HPV-58 (13.7%, 19/139), HPV-56 (11.5%, 16/139), HPV-51 (9.4%, 13/139) and HPV-18 (8.6%, 12/139). A total of 33.3% (12/36) patients positive for HPV-16 had cervical intraepithelial neoplasia (CIN)2 or a worse result, which was significantly higher than the prevalence of CIN2 of 1.8% (8/455) in patients negative for HPV-16 (Paged ≥51 years (38.7%) than in those aged ≤50 years (20.4%; P=0.036). Progression from persistent infection to CIN2 or worse (19/34, 55.9%) was higher than clearance (0/105, 0.0%; Page and long infection period with a clinical progression of CIN2 or worse. Therefore, LDA results may be presented as explanatory evidence during time-constrained patient-doctor consultations in order to deliver information regarding the patient's status. PMID:28587376

  4. The persistent stereotype: children's images of scientists

    Science.gov (United States)

    Emens McAdam, Janice

    1990-03-01

    Through their reading children learn to regard scientists as eccentrics. It is shown that this stereotype has persisted for over thirty years and affects many adult attitudes. Some methods of breaking the author-reader cycle are suggested.

  5. Associations between Exposure to Persistent Organic Pollutants in Childhood and Overweight up to 12 Years Later in a Low Exposed Danish Population

    DEFF Research Database (Denmark)

    Tang-Péronard, Jeanett L; Jensen, Tina K; Andersen, Helle R

    2015-01-01

    BACKGROUND: Persistent organic pollutants (POPs) have metabolic disrupting abilities and are suggested to contribute to the obesity epidemic. We investigated whether serum concentrations of POPs at 8-10 years of age were associated with subsequent development of overweight at age 14-16 and 20......-22 years. METHODS: The study was based on data from the European Youth Heart Study, Danish component (1997). Concentrations of several polychlorinated biphenyls (PCBs) and the organochlorine pesticides p,p-dichlorodiphenyldichloroethylene (DDE) and hexachlorobenzene (HCB) were measured in serum from...... children aged 8-10 years (n = 509). Information on BMI z-scores, waist circumference and % body fat were collected at clinical examinations at ages 8-10, 14-16 and 20-22 years. Multiple linear regression analyses were performed taking potential confounders into account. RESULTS: Overall, POP serum...

  6. Persistent postsurgical pain

    DEFF Research Database (Denmark)

    Werner, Mads Utke; Bischoff, Joakim Mutahi

    2014-01-01

    The prevalences of severe persistent postsurgical pain (PPP) following breast cancer surgery (BCS), groin hernia repair (GHR), and lung cancer surgery (LCS) are 13, 2, and 4-12 %, respectively. Estimates indicate that 80,000 patients each year in the U.S.A. are affected by severe pain...... duration of surgery, repeat surgery, more invasive surgical techniques, and intraoperative nerve lesion have been associated with PPP. One of the most consistent predictive factors for PPP is high intensity acute postsurgical pain, but also psychological factors including anxiety, catastrophizing trait...

  7. Return Persistence and Fund Flows in the Worst Performing Mutual Funds

    OpenAIRE

    Jonathan B. Berk; Ian Tonks

    2007-01-01

    We document that the observed persistence amongst the worst performing actively managed mutual funds is attributable to funds that have performed poorly both in the current and prior year. We demonstrate that this persistence results from an unwillingness of investors in these funds to respond to bad performance by withdrawing their capital. In contrast, funds that only performed poorly in the current year have a significantly larger (out)flow of funds/return sensitivity and consequently show...

  8. Persistence of canine distemper virus in the Greater Yellowstone Ecosystem's carnivore community

    Science.gov (United States)

    Almberg, E.S.; Cross, P.C.; Smith, D.W.

    2010-01-01

    Canine distemper virus (CDV) is an acute, highly immunizing pathogen that should require high densities and large populations of hosts for long-term persistence, yet CDV persists among terrestrial carnivores with small, patchily distributed groups. We used CDV in the Greater Yellowstone ecosystem's (GYE) wolves (Canis lupus) and coyotes (Canis latrans) as a case study for exploring how metapopulation structure, host demographics, and multi-host transmission affect the critical community size and spatial scale required for CDV persistence. We illustrate how host spatial connectivity and demographic turnover interact to affect both local epidemic dynamics, such as the length and variation in inter-epidemic periods, and pathogen persistence using stochastic, spatially explicit susceptible-exposed-infectious-recovered simulation models. Given the apparent absence of other known persistence mechanisms (e.g., a carrier or environmental state, densely populated host, chronic infection, or a vector), we suggest that CDV requires either large spatial scales or multi-host transmission for persistence. Current GYE wolf populations are probably too small to support endemic CDV. Coyotes are a plausible reservoir host, but CDV would still require 50 000-100 000 individuals for moderate persistence (>50% over 10 years), which would equate to an area of 1-3 times the size of the GYE (60000-200000 km2). Coyotes, and carnivores in general, are not uniformly distributed; therefore, this is probably a gross underestimate of the spatial scale of CDV persistence. However, the presence of a second competent host species can greatly increase the probability of long-term CDV persistence at much smaller spatial scales. Although no management of CDV is currently recommended for the GYE, wolf managers in the region should expect periodic but unpredictable CDV-related population declines as often as every 2-5 years. Awareness and monitoring of such outbreaks will allow corresponding

  9. Persistence of canine distemper virus in the Greater Yellowstone ecosystem's carnivore community.

    Science.gov (United States)

    Almberg, Emily S; Cross, Paul C; Smith, Douglas W

    2010-10-01

    Canine distemper virus (CDV) is an acute, highly immunizing pathogen that should require high densities and large populations of hosts for long-term persistence, yet CDV persists among terrestrial carnivores with small, patchily distributed groups. We used CDV in the Greater Yellowstone ecosystem's (GYE) wolves (Canis lupus) and coyotes (Canis latrans) as a case study for exploring how metapopulation structure, host demographics, and multi-host transmission affect the critical community size and spatial scale required for CDV persistence. We illustrate how host spatial connectivity and demographic turnover interact to affect both local epidemic dynamics, such as the length and variation in inter-epidemic periods, and pathogen persistence using stochastic, spatially explicit susceptible-exposed-infectious-recovered simulation models. Given the apparent absence of other known persistence mechanisms (e.g., a carrier or environmental state, densely populated host, chronic infection, or a vector), we suggest that CDV requires either large spatial scales or multi-host transmission for persistence. Current GYE wolf populations are probably too small to support endemic CDV. Coyotes are a plausible reservoir host, but CDV would still require 50000-100000 individuals for moderate persistence (> 50% over 10 years), which would equate to an area of 1-3 times the size of the GYE (60000-200000 km2). Coyotes, and carnivores in general, are not uniformly distributed; therefore, this is probably a gross underestimate of the spatial scale of CDV persistence. However, the presence of a second competent host species can greatly increase the probability of long-term CDV persistence at much smaller spatial scales. Although no management of CDV is currently recommended for the GYE, wolf managers in the region should expect periodic but unpredictable CDV-related population declines as often as every 2-5 years. Awareness and monitoring of such outbreaks will allow corresponding adjustments

  10. Persistence of Overseeded Cool-Season Grasses in Bermudagrass Turf

    OpenAIRE

    Thomas Serensits; Matthew Cutulle; Jeffrey F. Derr

    2011-01-01

    Cool-season grass species are commonly overseeded into bermudagrass turf for winter color. When the overseeded grass persists beyond the spring; however, it becomes a weed. The ability of perennial ryegrass, Italian (annual) ryegrass, intermediate ryegrass, and hybrid bluegrass to persist in bermudagrass one year after seeding was determined. Perennial ryegrass, intermediate ryegrass, and Italian ryegrass produced acceptable ground cover in the spring after fall seeding. Hybrid bluegrass di...

  11. A 9-year follow-up of a self-management group intervention for persistent neck pain in primary health care: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Gustavsson C

    2016-12-01

    Full Text Available Catharina Gustavsson,1,2 Lena von Koch1,3,4 1Center for Clinical Research Dalarna, Department of Public Health and Caring Science, Uppsala University, Uppsala, 2School of Education, Health and Social Studies, Dalarna University, Falun, 3Department of Neurobiology, Care Science and Society, Karolinska Institutet, 4Department of Neurology, Karolinska University Hospital, Stockholm, Sweden Background and objective: In previous short-term and 2-year follow-ups, a pain and stress self-management group intervention (PASS had better effect on pain-related disability, self-efficacy, catastrophizing, and perceived pain control than individually administered physiotherapy (IAPT for patients with persistent tension-type neck pain. Studies that have evaluated long-term effects of self-management approaches toward persistent neck pain are sparse. The objective of this study was to compare pain-related disability, self-efficacy for activities of daily living (ADL, catastrophizing, pain, pain control, use of analgesics, and health care utilization in people with persistent tension-type neck pain 9 years after they received the PASS or IAPT. Materials and methods: Of 156 people (PASS, n = 77; IAPT, n = 79 originally included in a randomized controlled trial, 129 people (PASS, n = 63; IAPT, n = 66 were eligible and were approached for the 9-year follow-up. They were sent a self-assessment questionnaire, comprising the Neck Disability Index, the Self-Efficacy Scale, the Coping Strategies Questionnaire, and questions regarding pain, analgesics, and health care utilization. Mixed linear models for repeated measures analysis or generalized estimating equations were used to evaluate the differences between groups and within groups over time (baseline, previous follow-ups, and 9-year follow-up and the interaction effect of “time by group”. Results: Ninety-four participants (73% responded (PASS, n = 48; IAPT, n = 46. At 9 years, PASS participants reported less

  12. IL-17A and serum amyloid A are elevated in a cigarette smoke cessation model associated with the persistence of pigmented macrophages, neutrophils and activated NK cells.

    Directory of Open Access Journals (Sweden)

    Michelle J Hansen

    Full Text Available While global success in cessation advocacy has seen smoking rates fall in many developed countries, persistent lung inflammation in ex-smokers is an increasingly important clinical problem whose mechanistic basis remains poorly understood. In this study, candidate effector mechanisms were assessed in mice exposed to cigarette smoke (CS for 4 months following cessation from long term CS exposure. BALF neutrophils, CD4+ and CD8+ T cells and lung innate NK cells remained significantly elevated following smoking cessation. Analysis of neutrophil mobilization markers showed a transition from acute mediators (MIP-2α, KC and G-CSF to sustained drivers of neutrophil and macrophage recruitment and activation (IL-17A and Serum Amyoid A (SAA. Follicle-like lymphoid aggregates formed with CS exposure and persisted with cessation, where they were in close anatomical proximity to pigmented macrophages, whose number actually increased 3-fold following CS cessation. This was associated with the elastolytic protease, MMP-12 (macrophage metallo-elastase which remained significantly elevated post-cessation. Both GM-CSF and CSF-1 were significantly increased in the CS cessation group relative to the control group. In conclusion, we show that smoking cessation mediates a transition to accumulation of pigmented macrophages, which may contribute to the expanded macrophage population observed in COPD. These macrophages together with IL-17A, SAA and innate NK cells are identified here as candidate persistence determinants and, we suggest, may represent specific targets for therapies directed towards the amelioration of chronic airway inflammation.

  13. Salt stress-induced transcription of σB- and CtsR-regulated genes in persistent and non-persistent Listeria monocytogenes strains from food processing plants.

    Science.gov (United States)

    Ringus, Daina L; Ivy, Reid A; Wiedmann, Martin; Boor, Kathryn J

    2012-03-01

    Listeria monocytogenes is a foodborne pathogen that can persist in food processing environments. Six persistent and six non-persistent strains from fish processing plants and one persistent strain from a meat plant were selected to determine if expression of genes in the regulons of two stress response regulators, σ(B) and CtsR, under salt stress conditions is associated with the ability of L. monocytogenes to persist in food processing environments. Subtype data were also used to categorize the strains into genetic lineages I or II. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure transcript levels for two σ(B)-regulated genes, inlA and gadD3, and two CtsR-regulated genes, lmo1138 and clpB, before and after (t=10 min) salt shock (i.e., exposure of exponential phase cells to BHI+6% NaCl for 10 min at 37°C). Exposure to salt stress induced higher transcript levels relative to levels under non-stress conditions for all four stress and virulence genes across all wildtype strains tested. Analysis of variance (ANOVA) of induction data revealed that transcript levels for one gene (clpB) were induced at significantly higher levels in non-persistent strains compared to persistent strains (p=0.020; two-way ANOVA). Significantly higher transcript levels of gadD3 (p=0.024; two-way ANOVA) and clpB (p=0.053; two-way ANOVA) were observed after salt shock in lineage I strains compared to lineage II strains. No clear association between stress gene transcript levels and persistence was detected. Our data are consistent with an emerging model that proposes that establishment of L. monocytogenes persistence in a specific environment occurs as a random, stochastic event, rather than as a consequence of specific bacterial strain characteristics.

  14. Mycobacterium Lysine ε-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level.

    Science.gov (United States)

    Duan, Xiangke; Li, Yunsong; Du, Qinglin; Huang, Qinqin; Guo, Siyao; Xu, Mengmeng; Lin, Yanping; Liu, Zhidong; Xie, Jianping

    2016-01-25

    Bacterial persisters, usually slow-growing, non-replicating cells highly tolerant to antibiotics, play a crucial role contributing to the recalcitrance of chronic infections and treatment failure. Understanding the molecular mechanism of persister cells formation and maintenance would obviously inspire the discovery of new antibiotics. The significant upregulation of Mycobacterium tuberculosis Rv3290c, a highly conserved mycobacterial lysine ε-aminotransferase (LAT) during hypoxia persistent model, suggested a role of LAT in persistence. To test this, a lat deleted Mycobacterium smegmatis was constructed. The expression of transcriptional regulator leucine-responsive regulatory protein (LrpA) and the amino acids abundance in M. smegmatis lat deletion mutants were lowered. Thus, the persistence capacity of the deletion mutant was impaired upon norfloxacin exposure under nutrient starvation. In summary, our study firstly reported the involvement of mycobacterium LAT in persister formation, and possibly through altering the intracellular amino acid metabolism balance.

  15. Measuring landscape-scale spread and persistence of an invaded submerged plant community from airborne remote sensing.

    Science.gov (United States)

    Santos, Maria J; Khanna, Shruti; Hestir, Erin L; Greenberg, Jonathan A; Ustin, Susan L

    2016-09-01

    Processes of spread and patterns of persistence of invasive species affect species and communities in the new environment. Predicting future rates of spread is of great interest for timely management decisions, but this depends on models that rely on understanding the processes of invasion and historic observations of spread and persistence. Unfortunately, the rates of spread and patterns of persistence are difficult to model or directly observe, especially when multiple rates of spread and diverse persistence patterns may be co-occurring over the geographic distribution of the invaded ecosystem. Remote sensing systematically acquires data over large areas at fine spatial and spectral resolutions over multiple time periods that can be used to quantify spread processes and persistence patterns. We used airborne imaging spectroscopy data acquired once a year for 5 years from 2004 to 2008 to map an invaded submerged aquatic vegetation (SAV) community across 2220 km 2 of waterways in the Sacramento-San Joaquin River Delta, California, USA, and measured its spread rate and its persistence. Submerged aquatic vegetation covered 13-23 km 2 of the waterways (6-11%) every year. Yearly new growth accounted for 40-60% of the SAV area, ~50% of which survived to following year. Spread rates were overall negative and persistence decreased with time. From this dataset, we were able to identify both radial and saltatorial spread of the invaded SAV in the entire extent of the Delta over time. With both decreasing spread rate and persistence, it is possible that over time the invasion of this SAV community could decrease its ecological impact. A landscape-scale approach allows measurements of all invasion fronts and the spatial anisotropies associated with spread processes and persistence patterns, without spatial interpolation, at locations both proximate and distant to the focus of invasion at multiple points in time. © 2016 by the Ecological Society of America.

  16. Spatial patterns of persistent neural activity vary with the behavioral context of short-term memory.

    Science.gov (United States)

    Daie, Kayvon; Goldman, Mark S; Aksay, Emre R F

    2015-02-18

    A short-term memory can be evoked by different inputs and control separate targets in different behavioral contexts. To address the circuit mechanisms underlying context-dependent memory function, we determined through optical imaging how memory is encoded at the whole-network level in two behavioral settings. Persistent neural activity maintaining a memory of desired eye position was imaged throughout the oculomotor integrator after saccadic or optokinetic stimulation. While eye position was encoded by the amplitude of network activity, the spatial patterns of firing were context dependent: cells located caudally generally were most persistent following saccadic input, whereas cells located rostrally were most persistent following optokinetic input. To explain these data, we computationally identified four independent modes of network activity and found these were differentially accessed by saccadic and optokinetic inputs. These results show how a circuit can simultaneously encode memory value and behavioral context, respectively, in its amplitude and spatial pattern of persistent firing. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation.

    Science.gov (United States)

    Nakai, K; Fujii, H; Ishimura, T; Fujisawa, M; Nishi, S

    Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 ± 74 mo vs 57 ± 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL) 2 , and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Antibody persistence 5 years after vaccination at 2 to 10 years of age with Quadrivalent MenACWY-CRM conjugate vaccine, and responses to a booster vaccination.

    Science.gov (United States)

    Block, Stan L; Christensen, Shane; Verma, Bikash; Xie, Fang; Keshavan, Pavitra; Dull, Peter M; Smolenov, Igor

    2015-04-27

    In a multi-center extension study, children 2-10 years of age, initially vaccinated with one or two doses (2-5 year-olds) or one dose (6-10 year-olds) of quadrivalent meningococcal CRM197-conjugate vaccine (MenACWY-CRM), were assessed five years later for antibody persistence and booster response using serum bactericidal assay with human complement (hSBA). Children 7-10 and 11-15 years of age, who received MenACWY-CRM in the original study, and age-matched vaccine-naïve children, were enrolled in this extension study. After an initial blood draw, children received one dose of MenACWY-CRM as booster or primary dose, with a second blood draw 28 days later. hSBA titers decreased five years after primary vaccination, but were higher than in non-vaccinated controls against serogroups C, W and Y, with substantial proportions having titers ≥8: 7-22% for A, 32-57% for C, 74-83% for W, and 48-54% for Y. Previously-vaccinated children demonstrated booster responses to revaccination against all four serogroups. Responses to primary vaccination in vaccine-naïve controls were lower and similar to primary responses observed in the original study. All vaccinations were generally well tolerated, with no safety concern raised. Approximately half the children vaccinated as 2-10 year-olds maintained protective antibodies against serogroups C, W and Y five years later, but fewer did against serogroup A. Declining titers five years after vaccination and robust booster responses suggest that five years may be an appropriate interval to revaccinate children, subject to epidemiology and delivery considerations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Short-Term Persistence of "DSM-IV" ADHD Diagnoses: Influence of Context, Age, and Gender

    Science.gov (United States)

    Bauermeister, Jose J.; Bird, Hector R.; Shrout, Patrick E.; Chavez, Ligia; Ramirez, Rafael; Canino, Glorisa

    2011-01-01

    Objective: Little is known about the effect of social context and gender on persistence of "attention-deficit/hyperactivity disorder" (ADHD) in children of early and middle school years. The study compared persistence of "DSM-IV" ADHD and ADHD not otherwise specified (NOS) over 2 years in two groups of Puerto Rican children.…

  20. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

    Directory of Open Access Journals (Sweden)

    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  1. Persistent producer-scrounger relationships in bats.

    Science.gov (United States)

    Harten, Lee; Matalon, Yasmin; Galli, Naama; Navon, Hagit; Dor, Roi; Yovel, Yossi

    2018-02-01

    Social foraging theory suggests that group-living animals gain from persistent social bonds, which lead to increased tolerance in competitive foraging and information sharing. Bats are among the most social mammals, often living in colonies of tens to thousands of individuals for dozens of years, yet little is known about their social foraging dynamics. We observed three captive bat colonies for over a year, quantifying >13,000 social foraging interactions. We found that individuals consistently used one of two foraging strategies, either producing (collecting) food themselves or scrounging it directly from the mouth of other individuals. Individual foraging types were consistent over at least 16 months except during the lactation period when females shifted toward producing. Scroungers intentionally selected whom to interact with when socially foraging, thus generating persistent nonrandom social relationships with two to three specific producers. These persistent producer-scrounger relationships seem to reduce aggression over time. Finally, scrounging was highly correlated with vigilance, and we hypothesize that vigilant-prone individuals turn to scrounging in the wild to mitigate the risk of landing on a potentially unsafe fruit tree. We find the bat colony to be a rich and dynamic social system, which can serve as a model to study the role that social foraging plays in the evolution of mammalian sociality. Our results highlight the importance of considering individual tendencies when exploring social behavior patterns of group-living animals. These tendencies further emphasize the necessity of studying social networks over time.

  2. Non-Dipole Features of the Geomagnetic Field May Persist for Millions of Years

    Science.gov (United States)

    Biasi, J.; Kirschvink, J. L.

    2017-12-01

    Here we present paleointensity results from within the South Atlantic Anomaly (SAA), which is a large non-dipole feature of the geomagnetic field. Within the area of the SAA, anomalous declinations, inclinations, and intensities are observed. Our results suggest that the SAA has been present for at least 5 Ma. This is orders-of-magnitude greater than any previous estimate, and suggests that some non-dipole features do not `average out' over geologic time, which is a fundamental assumption in all paleodirectional studies. The SAA has been steadily growing in size since the first magnetic measurements were made in the South Atlantic, and it is widely believed to have appeared 400 years ago. Recent studies from South Africa (Tarduno et al. (2015)) and Tristan da Cunha (Shah et al. (2016)) have suggested that the SAA has persisted for 1 ka and 96 ka respectively. We conducted paleointensity (PI) experiments on basaltic lavas from James Ross Island, on the Antarctic Peninsula. This large shield volcano has been erupting regularly over the last 6+ Ma (dated via Ar/Ar geochronology), and therefore contains the most complete volcanostratigraphic record in the south Atlantic. Our PI experiments used the Thellier-Thellier method, the IZZI protocol, and the same selection criteria as the Lawrence et al. (2009) study of Ross Island lavas (near McMurdo Station), which is the only comparable PI study on the Antarctic continent. We determined an average paleointensity at JRI of 13.8±5.2 μT, which is far lower than what we would expect from a dipole field (55 μT). In addition, this is far lower than the current value over James Ross Island of 36 μT. These results support the following conclusions: The time-averaged field model of Juarez et al. (1998) and Tauxe et al. (2013) is strongly favored by our PI data. The SAA has persisted over James Ross Island for at least 5 Ma, and has not drifted significantly over that time. The strength of non-dipole features such as the SAA

  3. Body fat and dairy product intake in lactase persistent and non-persistent children and adolescents.

    Science.gov (United States)

    Almon, Ricardo; Patterson, Emma; Nilsson, Torbjörn K; Engfeldt, Peter; Sjöström, Michael

    2010-06-16

    Lactase non-persistent (LNP) individuals may be lactose intolerant and therefore on a more restricted diet concerning milk and milk products compared to lactase persistent (LP) individuals. This may have an impact on body fat mass. This study examines if LP and LNP children and adolescents, defined by genotyping for the LCT-13910 C > T polymorphism, differ from each other with regard to milk and milk product intake, and measures of body fat mass. Children (n=298, mean age 9.6 years) and adolescents (n=386, mean age 15.6 years), belonging to the Swedish part of the European Youth Heart Study, were genotyped for the LCT-13910 C > T polymorphism. Dietary intakes of reduced and full-fat dairy varieties were determined. LNP (CC genotype) subjects consumed less milk, soured milk and yoghurt compared to LP (CT/TT genotype) subjects (pproducts than LP children and adolescents (p=0.009 for children and p=0.001 for adolescents). We conclude that LP is linked to an overall higher milk and dairy intake, but is not linked to higher body fat mass in children and adolescents.

  4. Persistent smoking as a predictor of disability pension due to musculoskeletal diagnoses: a 23 year prospective study of Finnish twins.

    Science.gov (United States)

    Ropponen, Annina; Korhonen, Tellervo; Svedberg, Pia; Koskenvuo, Markku; Silventoinen, Karri; Kaprio, Jaakko

    2013-12-01

    To investigate whether stability or changes in smoking predict disability pension (DP) due to low back diagnoses (LBD) and musculoskeletal diagnoses (MSD) after taking familial confounding into account using a co-twin design. Longitudinal smoking patterns and multiple covariates in a population-based cohort of 17,451 Finnish twins (6959 complete pairs) born before 1958 were surveyed through questionnaires in 1975 and 1981. The outcome data were collected from the national pension registers until the end of 2004. Cox proportional hazards regression models were used for statistical analyses. Disability pension due to low back diagnoses was granted to 408 individuals and disability pension due to musculoskeletal diagnoses to 1177 individuals during the follow-up of 23 years. Being a persistent smoker (current smoker both 1975 and 1981) predicted a significantly increased risk for disability pension (hazard ratio 1.69, 95% confidence interval 1.46, 1.97) compared to those individuals who had never smoked. The association remained when several confounding factors, including familial factors, were taken into account. Persistent smoking predicts early disability pension due to musculoskeletal diagnoses and low back diagnoses independently from numerous confounding factors, including familial effects shared by the co-twins. © 2013.

  5. Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity.

    Directory of Open Access Journals (Sweden)

    Melissa Starkey

    2014-08-01

    Full Text Available Etiological agents of acute, persistent, or relapsing clinical infections are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen that causes recalcitrant and severe acute chronic and persistent human infections. Here, we target the MvfR-regulated P. aeruginosa quorum sensing (QS virulence pathway to isolate robust molecules that specifically inhibit infection without affecting bacterial growth or viability to mitigate selective resistance. Using a whole-cell high-throughput screen (HTS and structure-activity relationship (SAR analysis, we identify compounds that block the synthesis of both pro-persistence and pro-acute MvfR-dependent signaling molecules. These compounds, which share a benzamide-benzimidazole backbone and are unrelated to previous MvfR-regulon inhibitors, bind the global virulence QS transcriptional regulator, MvfR (PqsR; inhibit the MvfR regulon in multi-drug resistant isolates; are active against P. aeruginosa acute and persistent murine infections; and do not perturb bacterial growth. In addition, they are the first compounds identified to reduce the formation of antibiotic-tolerant persister cells. As such, these molecules provide for the development of next-generation clinical therapeutics to more effectively treat refractory and deleterious bacterial-human infections.

  6. Trends in prescribing and persistence with antihypertensive therapy: results of the study PAPEETE (Population-based Analysis of Persistence and Economics of treatment with telmisartan study

    Directory of Open Access Journals (Sweden)

    Francesco Vittorio Costa

    2009-12-01

    Full Text Available This paper summarizes the results of the PAPEETE study (Population-based Analysis of PErsistence with treatment and Economics of TElmisartan that assessed trends in prescriptions, determinants and timing of treatment discontinuation and/or changes in antihypertensive drug therapy in a cohort of hypertensive patients living in Pavia. In the study were included all new users 18 years old or over receiving a first prescription for diuretics, beta-blockers, calcium channel-blockers, ACE inhibitors (ACEi or angiotensin receptor blockers (ARBs between 1 January 2003 and 31 December 2006. The follow-up period for each patient was 12 months starting from enrolment date. Based in the presence of continuous therapy, patients were defined as persistent and non-persistent users. A total of 61,493 patients was included in the study of whom 11.2% were persistent. Persistence with the treatment seems to be associated with patient-related factors and with the class of anti-hypertensive drug initially prescribed with the lowest persistence to antihypertensive treatment with diuretics (3.0% and the highest with ARBs (18.8%.

  7. Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

    Science.gov (United States)

    Dunne, Margaret R; Elliott, Louise; Hussey, Seamus; Mahmud, Nasir; Kelly, Jacinta; Doherty, Derek G; Feighery, Conleth F

    2013-01-01

    Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

  8. Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

    Directory of Open Access Journals (Sweden)

    Margaret R Dunne

    Full Text Available Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets, natural killer cells, CD56(+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

  9. Differences in Persistence and Graduation Rates of Black Students in Texas Community Colleges: A Multiyear, Statewide Study

    Science.gov (United States)

    Moss, Sheldon

    2017-01-01

    Purpose: The purpose of this journal-ready dissertation was to examine the 1-year and 2-year persistence rates of Black students in Texas community colleges for the 2007-2008 through the 2014-2015 academic years. Specifically, the relationship of the 1-year and 2-year persistence rates for Black students as a function of their institutional status…

  10. THE MOLECULAR MECHANISMS OF EPSTEINBARR VIRUS PERSISTENCE IN THE HUMAN ORGANISM

    Directory of Open Access Journals (Sweden)

    Volyanskiy A.Yu.

    2014-12-01

    Full Text Available This review describes advances in molecular aspects of EBV infection and disease. We discuss the spectrum of clinical illness due to EBV persistent infection. The main characteristic of Epstein-Barr virus (EBV is that initial infection results in lifelong persistence. EBV infects nearly all humans by the time they reach adulthood. Healthy humans have approximately 1 to 50 infected cells per million leukocytes. EBV is one of the eight known human herpesviruses. EBV virions have a doublestranded linear DNA and 100 genes had been described in virus genome. Initial infection is thought to occur in the oral compartment. The host cells of EBV are mainly lymphocytes and epithelial cells. EBV attaches to B cells via binding of the viral gp350 protein to CD21 receptor. The consequence of EBV infection is cells proliferation and differentiation into memory B lymphocyte in the germinal center. Infected memory B cells are released into the peripheral circulation. EBV persists mostly in the memory B cell. Latency is the state of persistent viral infection without active viral production. In latently infected B cells EBV virus exist as episomes. During the latent phase episomal replication occurs via host DNA polymerase. Genes of the nuclear antigens (EBNA and latent membrane proteins (LMP are transcribed during latency. These include EBNA1, EBNA2, EBNA3A, EBNA3B, EBNA3C, EBNA leader protein (EBNALP, LMP1 and LMP2 genes. All nuclear antigens are transcription transactivators which bind to cis-regulatory DNA elements of cell or virus genomes directly or in complex with other proteins. LMP2A and LMP1 can function to coordinately mimic B-cell receptor and CD40 coreceptor signaling in latently infected B cells. LMP proteins activate cell signaling systems and as the consequence different gene expression programs. Characterization of gene expression patterns in different cell lines and pathologic conditions has revealed that there are at least three different

  11. [Persistent duodenal septum in an adult].

    Science.gov (United States)

    Helwing, E; Echtermeyer, V; Otten, G

    1977-02-01

    A case of duodenal obstruction by a congenital duodenal web in a 34-year-old woman is presented. A mucosal diaphragm obstructed the duodenum. It showed an excentric opening of 0.8 cm diameter, but the dilated diaphragm caused a total stop during the last months. Despite a typical history, exact X-ray, and endoscopic examination, the correct preoperative diagnosis was not found, because nobody thought it possible, that a mucosal diapharm of the duodenum could persist for 34 years.

  12. Murid herpesvirus-4 exploits dendritic cells to infect B cells.

    Directory of Open Access Journals (Sweden)

    Miguel Gaspar

    2011-11-01

    Full Text Available Dendritic cells (DCs play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4, infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells.

  13. The origins of lactase persistence in Europe.

    Directory of Open Access Journals (Sweden)

    Yuval Itan

    2009-08-01

    Full Text Available Lactase persistence (LP is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (-13,910 C/T indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the--13,910*T (derived allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on--13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the--13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.

  14. The origins of lactase persistence in Europe.

    Science.gov (United States)

    Itan, Yuval; Powell, Adam; Beaumont, Mark A; Burger, Joachim; Thomas, Mark G

    2009-08-01

    Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (-13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the--13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on--13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the--13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.

  15. Can patients at risk for persistent negative symptoms be identified during their first episode of psychosis?

    Science.gov (United States)

    Malla, Ashok K; Norman, Ross M G; Takhar, Jatinder; Manchanda, Rahul; Townsend, Laurel; Scholten, Derek; Haricharan, Raj

    2004-07-01

    Patients with schizophrenia who show persistent negative symptoms are an important subgroup, but they are difficult to identify early in the course of illness. The objective of this study was to examine characteristics that discriminate between first-episode psychosis (FEP) patients in whom primary negative symptoms did or did not persist after 1 year of treatment. Patients with a DSM-IV diagnosis of FEP whose primary negative symptoms did (N = 36) or did not (N = 35) persist at 1 year were contrasted on their baseline and 1-year characteristics. Results showed that patients with persistent primary negative symptoms (N = 36) had a significantly longer duration of untreated psychosis (p < .005), worse premorbid adjustment during early (p < .001) and late adolescence (p < .01), and a higher level of affective flattening (p < .01) at initial presentation compared with patients with transitory primary negative symptoms. The former group also showed significantly lower remission rates at 1 year (p < .001). Multiple regression analysis confirmed the independent contribution of duration of untreated psychosis, premorbid adjustment, and affective flattening at baseline to the patients' likelihood of developing persistent negative symptoms. It may therefore be possible to distinguish a subgroup of FEP patients whose primary negative symptoms are likely to persist on the basis of characteristics shown at initial presentation for treatment.

  16. Persistence versus extinction for a class of discrete-time structured population models.

    Science.gov (United States)

    Jin, Wen; Smith, Hal L; Thieme, Horst R

    2016-03-01

    We provide sharp conditions distinguishing persistence and extinction for a class of discrete-time dynamical systems on the positive cone of an ordered Banach space generated by a map which is the sum of a positive linear contraction A and a nonlinear perturbation G that is compact and differentiable at zero in the direction of the cone. Such maps arise as year-to-year projections of population age, stage, or size-structure distributions in population biology where typically A has to do with survival and individual development and G captures the effects of reproduction. The threshold distinguishing persistence and extinction is the principal eigenvalue of (II−A)(−1)G'(0) provided by the Krein-Rutman Theorem, and persistence is described in terms of associated eigenfunctionals. Our results significantly extend earlier persistence results of the last two authors which required more restrictive conditions on G. They are illustrated by application of the results to a plant model with a seed bank.

  17. Long-term persistence of pioneer species in tropical forest soil seed banks

    Energy Technology Data Exchange (ETDEWEB)

    Dalling, J W; Brown, T A

    2008-10-05

    In tropical forests, pioneer species regenerate from seeds dispersed directly into canopy gaps, and from seeds that persisted in soil seed banks before gap formation. However, life-history models suggest that selection for long-term persistence of seeds in soil should be weak, as persistence incurs a fitness cost resulting from prolonged generation time. We use a carbon dating technique to provide the first direct measurements of seed persistence in undisturbed tropical forest seed banks. We show that seeds germinate successfully from surface soil microsites up to 38 years after dispersal. Decades-long persistence may be common in pioneers with relatively large mass, and appears to be unrelated to specific regeneration requirements. In Croton billbergianus, a sub-canopy tree that recruits in abundant small gaps, long-term persistence is associated with short-distance ballistic seed dispersal. In Trema micrantha, a canopy tree with widespread dispersal, persistence is associated with a requirement for large gaps that form infrequently in old-growth forest.

  18. Primary reflex persistence in children with reading difficulties (dyslexia): a cross-sectional study.

    Science.gov (United States)

    McPhillips, Martin; Jordan-Black, Julie-Anne

    2007-03-02

    The primary reflex system emerges during fetal life and is inhibited during the first year after birth. Our aim was to examine the effects of persistence of this early neurological system on the attainment of core literacy skills in dyslexic and non-dyslexic poor readers. We assessed the prevalence of a persistent primary reflex in a cross-sectional, representative sample of children (n=739) aged 7-9 years old attending mainstream primary school in Northern Ireland using standardised educational tests, and a clinical diagnostic test for a primary reflex (the asymmetrical tonic neck reflex (ATNR)). Multiple regression analyses, involving all of the sample children, revealed that persistence of the ATNR was significantly predictive of attainments in reading (t=-8.34, pschooling, the attainment of core educational skills may be affected by the persistence of a brainstem mediated reflex system that should have been inhibited in the first year after birth. Furthermore, these findings suggest that dyslexia is not a distinct category of poor reading, and that it may be more valid to term all poor readers as dyslexic irrespective of IQ.

  19. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro

    Directory of Open Access Journals (Sweden)

    Brianna K. Swartwout

    2017-10-01

    Full Text Available Zika virus (ZIKV has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  20. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro.

    Science.gov (United States)

    Swartwout, Brianna K; Zlotnick, Marta G; Saver, Ashley E; McKenna, Caroline M; Bertke, Andrea S

    2017-10-13

    Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  1. Follow-up of 5- to 11-year-old children treated for persistent pulmonary hypertension of the newborn

    DEFF Research Database (Denmark)

    Eriksen, Vibeke; Nielsen, Lars Holme; Klokker, Mads

    2009-01-01

    AIM: Determine the prevalence of sensorineural hearing loss (SNHL) and relate this to cumulative exposure to hypoxia, hypocapnia and hypotension. Describe chronic health problems among 5- to 11-year-old children treated for persistent pulmonary hypertension of the newborn (PPHN). METHODS: The index...... group consisted of 85 children and a reference group was matched for age, sex and municipality of current residence. Questionnaires were sent to the families. The families in the index group were asked to participate in an examination of their child's hearing. RESULTS: Seven children (11%) had SNHL...... therapy compared with 8% in the reference group (chi-square test, p = 0.028). In the index group five children had cerebral palsy and two had developmental delay. Nineteen percent in the index group and 5% in the reference group had remedial education (chi-square test, p = 0.008). CONCLUSION: Children...

  2. Persistence of antimuscarinic drug use

    DEFF Research Database (Denmark)

    Brostrøm, Søren; Hallas, Jesper

    2009-01-01

    PURPOSE: Evidence suggests antimuscarinic drugs for the overactive-bladder syndrome only confer modest improvements in quality of life. We wanted to describe the persistence of therapy, including an extended analysis beyond the 1-year follow-up employed in other studies. METHODS: All prescriptions...... for drugs in ATC category G04BD were retrieved for the period 1999-2006 from a regional database with complete capture of all reimbursed prescriptions. Kaplan-Meyer curves were generated for duration of treatment for each substance and analyzed for determinants of termination. RESULTS: With the exception...... of trospium chloride, all drugs had continuation rates of less than 50% at 6 months, less than 25% at 1 year, and less than 10% at 2 years and longer. Trospium chloride, however, exhibited continuation rates of 46% at 6 months, 36% at 1 year, 22% at 2 years, and 16% at 3 years. CONCLUSIONS: In a setting...

  3. Does the African-American-white mortality gap persist after playing professional basketball? A 59-year historical cohort study.

    Science.gov (United States)

    Lawler, Tyler; Lawler, Frank; Gibson, Jack; Murray, Rachael

    2012-06-01

    The African-American-white mortality gap for males in the United States is 6 years in favor of whites. Participation in professional sport may moderate this ethnic disparity. The historical cohort of professional basketball players, with nearly equal numbers of African-American and white players, can provide a natural experiment that may control for the classic confounders of income, education, socioeconomic status (SES), and physical factors related to mortality. The objectives of this study are to assess mortality and calculate survival for the overall study population and within ethnicity. Data were combined from several publicly available sources. The cohort was analyzed to compare longevity among all players, and for players stratified by ethnicity, with the general U.S. population. The final dataset included 3366 individuals, of whom 56.0% were African American. Results suggest white players live 18 months longer than their African-American colleagues. African-American players gained 9 years on their respective referent and live longer than white men in the general public. After controlling for covariates, we found that African-American players have a 75% increased risk of death compared with white players, a statistically significant gap (p gap for males is largely ameliorated (1.5 years vs. 6.1 years) in professional basketball but still persists. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Risk factors associated with incidence and persistence of frequent headaches.

    Science.gov (United States)

    Marklund, Susanna; Häggman-Henrikson, Birgitta; Wänman, Anders

    2014-11-01

    Headaches represent a significant public health problem, but the knowledge of factors specifically related to incidence and persistence of headaches is still limited. The aim of this study was to evaluate whether gender, self-reported bruxism and variations in the dental occlusion contribute to onset and persistence of frequent headaches. The study population comprised 280 dental students, examined annually in a 2-year prospective study with a questionnaire and a clinical examination of the jaw function. In the analysis subjects were dichotomized into cases with frequent (once a week or more) or without frequent headaches (controls). The 2-year cumulative incidence was based on subjects without frequent headaches at baseline. Cases with 2-year persistent headaches reported such symptoms at all three examinations. Self-reported bruxism and factors in the dental occlusion at baseline were used as independent variables in logistic regression analyses. The 2-year cumulative incidence of frequent headaches was 21%. Female gender (OR = 2.6; CI = 1.3-5.4), self-reported bruxism (OR = 2.3; CI = 1.2-4.4) and mandibular instability in intercuspal position (OR = 3.2; CI = 1.4-7.5) were associated with incidence of frequent headaches. Persistent headaches during the observation period were present in 12 individuals (4%) and significantly related to mandibular instability in intercuspal position (OR = 6.1; CI = 1.6-22.6). The results indicate that female gender, self-reported bruxism and mandibular instability in intercuspal position are of importance in the development of frequent headaches. In management of these patients a multidisciplinary approach including dentists may be important and, thus, advocated.

  5. Hyperthyroidism as a cause of persistent vomiting.

    NARCIS (Netherlands)

    Hoogendoorn, E.H.; Cools, B.M.

    2004-01-01

    A 32-year-old woman presented with persistent vomiting, epigastric pain and weight loss. A sinus tachycardia was the clue to the diagnosis of hyperthyroidism due to Graves' disease. On treatment with propylthiouracil and a beta-blocking agent, her symptoms resolved within one day, even though her

  6. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines

    DEFF Research Database (Denmark)

    Salik, Elaha; Løvik, Ida; Andersen, Klaus E

    2016-01-01

    There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year...... period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons...... treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations....

  7. Association Between Persistent Pain and Memory Decline and Dementia in a Longitudinal Cohort of Elders.

    Science.gov (United States)

    Whitlock, Elizabeth L; Diaz-Ramirez, L Grisell; Glymour, M Maria; Boscardin, W John; Covinsky, Kenneth E; Smith, Alexander K

    2017-08-01

    Chronic pain is common among the elderly and is associated with cognitive deficits in cross-sectional studies; the population-level association between chronic pain and longitudinal cognition is unknown. To determine the population-level association between persistent pain, which may reflect chronic pain, and subsequent cognitive decline. Cohort study with biennial interviews of 10 065 community-dwelling older adults in the nationally representative Health and Retirement Study who were 62 years or older in 2000 and answered pain and cognition questions in both 1998 and 2000. Data analysis was conducted between June 24 and October 31, 2016. "Persistent pain," defined as a participant reporting that he or she was often troubled with moderate or severe pain in both the 1998 and 2000 interviews. Coprimary outcomes were composite memory score and dementia probability, estimated by combining neuropsychological test results and informant and proxy interviews, which were tracked from 2000 through 2012. Linear mixed-effects models, with random slope and intercept for each participant, were used to estimate the association of persistent pain with slope of the subsequent cognitive trajectory, adjusting for demographic characteristics and comorbidities measures in 2000 and applying sampling weights to represent the 2000 US population. We hypothesized that persistent pain would predict accelerated memory decline and increased probability of dementia. To quantify the impact of persistent pain on functional independence, we combined our primary results with information on the association between memory and ability to manage medications and finances independently. Of the 10 065 eligible HRS sample members, 60% were female, and median baseline age was 73 years (interquartile range, 67-78 years). At baseline, persistent pain affected 10.9% of participants and was associated with worse depressive symptoms and more limitations in activities of daily living. After covariate

  8. Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Stina Axelsson

    Full Text Available A phase II clinical trial with glutamic acid decarboxylase (GAD 65 formulated with aluminium hydroxide (GAD-alum has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D. We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC were stimulated in vitro with GAD(65. Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65 autoantibody (GADA levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD(65, but not with control antigens, compared with placebo subjects. GAD(65-induced T-cell activation was accompanied by secretion of T helper (Th 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65 enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD(65-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65 immunity.

  9. Performance persistence in institutional investment management: The case of Chinese equity funds

    Directory of Open Access Journals (Sweden)

    Zia-ur-Rehman Rao

    2016-09-01

    Full Text Available This paper investigates the performance and persistence in performance of equity funds in China. We apply the capital asset pricing model (CAPM and the Carhart four-factor model to examine 520 equity funds for an eleven-year period with 39,449 observations. To investigate persistence, the entire sample is divided into ten portfolios (deciles on the basis of lagged one-year performance and then observed over the next 12 months. We find that equity funds in China outperform their benchmark market but do not find any evidence of persistence in the performance of equity funds. Top-performing (worst-performing funds do not continue to perform well (worse in the following year. Top-performing funds are younger and have lower expense ratios than the worst-performing funds. However, the size of the top-performing funds and the worst-performing funds show no significant difference. Our results suggest that past performance of equity funds is not predictive of future fund performance.

  10. Persistence of undergraduate women in STEM fields

    Science.gov (United States)

    Pedone, Maggie Helene

    The underrepresentation of women in science, technology, engineering, and mathematics (STEM) is a complex problem that continues to persist at the postsecondary level, particularly in computer science and engineering fields. This dissertation explored the pre-college and college level factors that influenced undergraduate women's persistence in STEM. This study also examined and compared the characteristics of undergraduate women who entered STEM fields and non-STEM fields in 2003-2004. The nationally representative Beginning Postsecondary Students Longitudinal Study (BPS:04/09) data set was used for analysis. BPS:04/09 study respondents were surveyed three times (NPSAS:04, BPS:04/06, BPS:04/09) over a six-year period, which enabled me to explore factors related to long-term persistence. Astin's Input-Environment-Output (I-E-O) model was used as the framework to examine student inputs and college environmental factors that predict female student persistence (output) in STEM. Chi-square tests revealed significant differences between undergraduate women who entered STEM and non-STEM fields in 2003-2004. Differences in student demographics, prior academic achievement, high school course-taking patterns, and student involvement in college such as participation in study groups and school clubs were found. Notably, inferential statistics showed that a significantly higher proportion of female minority students entered STEM fields than non-STEM fields. These findings challenge the myth that underrepresented female minorities are less inclined to enter STEM fields. Logistic regression analyses revealed thirteen significant predictors of persistence for undergraduate women in STEM. Findings showed that undergraduate women who were younger, more academically prepared, and academically and socially involved in college (e.g., lived on campus, interacted with faculty, participated in study groups, fine arts activities, and school sports) were more likely to persist in STEM

  11. T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Allison S Thomas

    2017-09-01

    Full Text Available HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART, these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18. Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that

  12. Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

    Science.gov (United States)

    Chen, Hui-Chi; Schiffman, Mark; Lin, Ching-Yu; Pan, Mei-Hung; You, San-Lin; Chuang, Li-Chung; Hsieh, Chang-Yao; Liaw, Kai-Li; Hsing, Ann W; Chen, Chien-Jen

    2011-09-21

    Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma. At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method. Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age. HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.

  13. Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression

    DEFF Research Database (Denmark)

    Jin, Xin; Nowell, Craig S; Ulyanchenko, Svetlana

    2014-01-01

    does not require FOXN1. Here, we have used a revertible severely hypomorphic allele of Foxn1, Foxn1R, to test the stability of the common TEPC in vivo. By reactivating Foxn1 expression postnatally in Foxn1R/- mice we demonstrate that functional TEPCs can persist in the thymic rudiment until at least 6...... months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression, suggesting that manipulation of FOXN1 activity may prove...... a valuable method for long term maintenance of TEPC in vitro....

  14. Genome Sequencing Identifies Two Nearly Unchanged Strains of Persistent Listeria monocytogenes Isolated at Two Different Fish Processing Plants Sampled 6 Years Apart

    DEFF Research Database (Denmark)

    Holch, Anne; Webb, Kristen; Lukjancenko, Oksana

    2013-01-01

    Listeria monocytogenes is a food-borne human-pathogenic bacterium that can cause infections with a high mortality rate. It has a remarkable ability to persist in food processing facilities. Here we report the genome sequences for two L. monocytogenes strains (N53-1 and La111) that were isolated 6...... that has been isolated as a persistent subtype in several European countries. The purpose of this study was to use genome analyses to identify genes or proteins that could contribute to persistence. In a genome comparison, the two persistent strains were extremely similar and collectively differed from...... are required to determine if the absence of these genes promotes persistence. While the genome comparison did not point to a clear physiological explanation of the persistent phenotype, the remarkable similarity between the two strains indicates that subtypes with specific traits are selected for in the food...

  15. Early developmental trajectories of number knowledge and math achievement from 4 to 10 years: Low-persistent profile and early-life predictors.

    Science.gov (United States)

    Garon-Carrier, Gabrielle; Boivin, Michel; Lemelin, Jean-Pascal; Kovas, Yulia; Parent, Sophie; Séguin, Jean R; Vitaro, Frank; Tremblay, Richard E; Dionne, Ginette

    2018-06-01

    Little is known about the development of number knowledge (NK) and the antecedents of low-persistent NK profiles in early childhood. We documented the developmental trajectories of NK across the transition from preschool to elementary school, their predictive validity with respect to later math achievement, and the child and family early-life factors associated with low NK profiles. Children's NK was assessed four times at regular intervals between the ages 4 and 7 years in a large, representative population-based sample. Developmental trajectories of NK were established for 1597 children. These children were also assessed with respect to several features of their family environment at 5, 17, and 29 months, as well as their cognitive skills at age 41 months. Analyses revealed a best-fitting 4-trajectory model, characterized by Low-Increasing (10% of the children), Moderate-Increasing (39%), Moderate-Fast Increasing (32%) and High-Increasing (19%) groups. Children of these trajectory groups differed significantly with respect to math achievement at ages 8 and 10 years, with the Low-Increasing group persistently scoring lower than the other groups throughout these years. Children of Low-Increasing NK group were from household of lower income and father with low educational background, poorer early cognitive development, and more importantly, reduced visual-spatial skills and memory-span. Children displaying reduced cognitive abilities and impoverished living conditions early in life are at greater risk of low NK throughout late preschool and school entry, with ensuing difficulties in math achievement. They deserve early preventive attention to help alleviate later mathematic difficulties. Copyright © 2018 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  16. Eye on the B-ALL: B-cell receptor repertoires reveal persistence of numerous B-lymphoblastic leukemia subclones from diagnosis to relapse

    Science.gov (United States)

    Bashford-Rogers, R J M; Nicolaou, K A; Bartram, J; Goulden, N J; Loizou, L; Koumas, L; Chi, J; Hubank, M; Kellam, P; Costeas, P A; Vassiliou, G S

    2016-01-01

    The strongest predictor of relapse in B-cell acute lymphoblastic leukemia (B-ALL) is the level of persistence of tumor cells after initial therapy. The high mutation rate of the B-cell receptor (BCR) locus allows high-resolution tracking of the architecture, evolution and clonal dynamics of B-ALL. Using longitudinal BCR repertoire sequencing, we find that the BCR undergoes an unexpectedly high level of clonal diversification in B-ALL cells through both somatic hypermutation and secondary rearrangements, which can be used for tracking the subclonal composition of the disease and detect minimal residual disease with unprecedented sensitivity. We go on to investigate clonal dynamics of B-ALL using BCR phylogenetic analyses of paired diagnosis-relapse samples and find that large numbers of small leukemic subclones present at diagnosis re-emerge at relapse alongside a dominant clone. Our findings suggest that in all informative relapsed patients, the survival of large numbers of clonogenic cells beyond initial chemotherapy is a surrogate for inherent partial chemoresistance or inadequate therapy, providing an increased opportunity for subsequent emergence of fully resistant clones. These results frame early cytoreduction as an important determinant of long-term outcome. PMID:27211266

  17. Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years.

    Directory of Open Access Journals (Sweden)

    Pam Factor-Litvak

    Full Text Available Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age.In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP, butylbenzyl phthalate (BBzP, di-isobutyl phthalate (DiBP, di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ.Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b = -2.69 (95% confidence interval [CI] = -4.33, -1.05 and b = -2.69 (95% CI = -4.22, -1.16 per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI = 1.9, 11.4 and 7.6 (95% CI = 3.2, 12.1 points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning.Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children's intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.

  18. Numeric invariants from multidimensional persistence

    Energy Technology Data Exchange (ETDEWEB)

    Skryzalin, Jacek [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carlsson, Gunnar [Stanford Univ., Stanford, CA (United States)

    2017-05-19

    In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be used to study data.

  19. Reflections on Student Persistence

    Directory of Open Access Journals (Sweden)

    Vincent Tinto

    2017-07-01

    Full Text Available The Feature for this issue Reflections on Student Persistence has been prepared by Professor Vincent Tinto, Distinguished University Professor Emeritus at Syracuse University, United States of America (USA and a longtime friend and supporter of STARS. Vincent explores the case for motivation to be considered as a significant aspect of the tertiary student psyche by drawing on theoretical frameworks, research and practical experiences related to the issue. He synthesises this extensive, detailed, rich but often somewhat impenetrable data into a trilogy of clear and credible key dimensions of the motivation construct student self efficacy, sense of belonging and perceived value of the curriculum. This interpretation of the literature is a personal but informed reflection and is a timely piece which highlights the breadth and profundity of the presentations at this year's conference in Adelaide, Australia where students in all their diversity are central to our focus on enhancing the student experience. In this opening article, Vincent refers directly to the STARS papers selected for this Conference issue of the Journal which also address the importance of student persistence, self-efficacy and building the sense of belonging within their own institutional communities (Fernandes, Ford, Rayner & Pretorius; Kahu, Nelson, & Picton; McFarlane, Spes-Skrbis & Taib; Naylor; Smallhorn. Echoing his position on social justice and his advocacy for underserved students, Vincent reminds us that educational equity gaps still exist, and he encourages us to see the issue of persistence through the eyes of the students to support their perseverance and completion and thereby help reduce educational disadvantage.

  20. Persistent Aerial Tracking

    KAUST Repository

    Mueller, Matthias

    2016-01-01

    persistent, robust and autonomous object tracking system for unmanned aerial vehicles (UAVs) called Persistent Aerial Tracking (PAT). A computer vision and control strategy is applied to a diverse set of moving objects (e.g. humans, animals, cars, boats, etc

  1. Living with persistent rheumatoid arthritis: a BARFOT study.

    Science.gov (United States)

    Bala, Sidona-Valentina; Samuelson, Karin; Hagell, Peter; Fridlund, Bengt; Forslind, Kristina; Svensson, Björn; Thomé, Bibbi

    2017-09-01

    To describe and understand the meaning of living with persistent rheumatoid arthritis. A considerable number of patients with rheumatoid arthritis live with an ongoing active and symptomatic illness despite access to potent antirheumatic treatment. There is, however, a lack of knowledge about the meaning of living with this severe long-term illness, defined as persistent rheumatoid arthritis. A descriptive design based on a hermeneutic phenomenological method was used. Ten adults with persistent rheumatoid arthritis and at least five years disease duration were interviewed. The interviews were analysed according to van Manen's method. Living with persistent rheumatoid arthritis revealed four overall themes: an existence dominated by painful symptoms and treatment, radical changes and limitations in one's life, a continual struggle to cope with one's life and to master the illness, and a dependency on those who are close by and the world around. The lifeworld was affected to a varying extent and in various ways by the illness but also by the dependence on its treatment and care that was not experienced as sufficiently meeting needs in terms of security, access to and coordination of care as well as team and rehabilitation services. Persistent rheumatoid arthritis and its treatment entail a radical effect on the person's life and quality of life. Current ordinary rheumatology care does not seem to meet the individual needs of the person with persistent rheumatoid arthritis in an optimal way. A greater knowledge about and understanding of the person who lives with persistent rheumatoid arthritis is important for facilitating the development of care and the relief of suffering. A holistic alternative to conventional clinical practice, such as person-centred care, could be tested as an innovative model of care. Our findings might serve as material for educational and counselling purposes for healthcare professionals. © 2016 John Wiley & Sons Ltd.

  2. Demonstration of persistent contamination of a cooked egg product production facility with Salmonella enterica serovar Tennessee and characterization of the persistent strain.

    Science.gov (United States)

    Jakočiūnė, D; Bisgaard, M; Pedersen, K; Olsen, J E

    2014-08-01

    The aim of this study was to investigate whether continuous contamination of light pasteurized egg products with Salmonella enterica serovar Tennessee (S. Tennessee) at a large European producer of industrial egg products was caused by persistent contamination of the production facility and to characterize the persistent strains. Seventy-three S. Tennessee isolates collected from products over a 3-year period with intermittent contamination, and 15 control strains were compared by pulsed field gel electrophoresis (PFGE) using two enzymes. Forty-five case isolates distributed throughout the full period were shown to belong to one profile type. Isolates representing different PFGE profiles were all assigned to ST 319 by multilocus sequence typing (MLST). The case isolates did not show a higher ability to form biofilm on a plastic surface than noncase isolates. Characteristically, members of the persistent clone were weak producers of H2 S in laboratory medium. S. Tennessee isolated from the case was able to grow better in pasteurized egg product compared with other serovars investigated. It was concluded that the contamination was caused by a persistent strain in the production facility and that this strain apparently had adapted to grow in the relevant egg product. S. Tennessee has previously been associated with persistence in hatching facilities. This is the first report of persistent contamination of an egg production facility with this serovar. © 2014 The Society for Applied Microbiology.

  3. Risk factors for persistent atrial fibrillation following successful hyperthyroidism treatment with radioiodine therapy.

    Science.gov (United States)

    Zhou, Zhen-Hu; Ma, Long-Le; Wang, Le-Xin

    2011-01-01

    To investigate the predicting factors for persistent atrial fibrillation (AF) following radioiodine therapy for hyperthyroidism. Standard 12-lead ECG and 24-h Holter monitoring were performed in 94 patients (38 males, mean age 46.1±8.2 years) with persistent AF following radioiodine therapy for hyperthyroidism. Left ventricular (LV) function was assessed with two-dimensional echocardiography. Euthyroidism or hypothyroidism was achieved in 81% and 19% of the patients, respectively, after radioiodine therapy. At the end of follow-up (1.6±1.3 years), LV ejection fraction in the 52 patients with LV dysfunction was increased from 39.3±3.3% to 59.0±5.5% (ptreatment paroxysmal AF, no AF was documented during the follow-up. In the 45 patients with pre-treatment persistent AF, AF was found in 27 (60%) during the follow-up. Multivariate logistic regression analysis showed that more than 55 years old in age (RR 2.76, 95% CI: 1.16-8.79, phyperthyroidism (RR 3.08, 95% CI: 1.22-11.41, ptreatment atrial fibrillation (RR 2.96, 95% CI: 1.31-7.68, phyperthyroidism and pre-treatment duration of AF are risk factors for persistent AF following radioiodine therapy.

  4. The effect of emotion on articulation rate in persistence and recovery of childhood stuttering.

    Science.gov (United States)

    Erdemir, Aysu; Walden, Tedra A; Jefferson, Caswell M; Choi, Dahye; Jones, Robin M

    2018-06-01

    This study investigated the possible association of emotional processes and articulation rate in pre-school age children who stutter and persist (persisting), children who stutter and recover (recovered) and children who do not stutter (nonstuttering). The participants were ten persisting, ten recovered, and ten nonstuttering children between the ages of 3-5 years; who were classified as persisting, recovered, or nonstuttering approximately 2-2.5 years after the experimental testing took place. The children were exposed to three emotionally-arousing video clips (baseline, positive and negative) and produced a narrative based on a text-free storybook following each video clip. From the audio-recordings of these narratives, individual utterances were transcribed and articulation rates were calculated. Results indicated that persisting children exhibited significantly slower articulation rates following the negative emotion condition, unlike recovered and nonstuttering children whose articulation rates were not affected by either of the two emotion-inducing conditions. Moreover, all stuttering children displayed faster rates during fluent compared to stuttered speech; however, the recovered children were significantly faster than the persisting children during fluent speech. Negative emotion plays a detrimental role on the speech-motor control processes of children who persist, whereas children who eventually recover seem to exhibit a relatively more stable and mature speech-motor system. This suggests that complex interactions between speech-motor and emotional processes are at play in stuttering recovery and persistency; and articulation rates following negative emotion or during stuttered versus fluent speech might be considered as potential factors to prospectively predict persistence and recovery from stuttering. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Income and financial aid effects on persistence and degree attainment in public colleges

    Directory of Open Access Journals (Sweden)

    Alicia C. Dowd

    2004-05-01

    Full Text Available This study examined the distribution of financial aid among financially dependent four-year college students and the effectiveness of different types of financial aid in promoting student persistence and timely bachelor’s degree attainment. The findings of descriptive statistical and logistic regression analyses using the NCES Beginning Postsecondary Students (1990-94 data show that subsidized loans taken in the first year of college have a positive effect on persistence. The first-year distribution of aid does not close the income gap in bachelor’s degree attainment. Living on campus and first-year grade point average are the most important predictors of timely degree completion.

  6. CD4 T Cell Responses in Latent and Chronic Viral Infections

    Science.gov (United States)

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  7. The commensal infant gut meta-mobilome as a potential reservoir for persistent multidrug resistance integrons.

    Science.gov (United States)

    Ravi, Anuradha; Avershina, Ekaterina; Foley, Steven L; Ludvigsen, Jane; Storrø, Ola; Øien, Torbjørn; Johnsen, Roar; McCartney, Anne L; L'Abée-Lund, Trine M; Rudi, Knut

    2015-10-28

    Despite the accumulating knowledge on the development and establishment of the gut microbiota, its role as a reservoir for multidrug resistance is not well understood. This study investigated the prevalence and persistence patterns of an integrase gene (int1), used as a proxy for integrons (which often carry multiple antimicrobial resistance genes), in the fecal microbiota of 147 mothers and their children sampled longitudinally from birth to 2 years. The study showed the int1 gene was detected in 15% of the study population, and apparently more persistent than the microbial community structure itself. We found int1 to be persistent throughout the first two years of life, as well as between mothers and their 2-year-old children. Metagenome sequencing revealed integrons in the gut meta-mobilome that were associated with plasmids and multidrug resistance. In conclusion, the persistent nature of integrons in the infant gut microbiota makes it a potential reservoir of mobile multidrug resistance.

  8. Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder.

    Directory of Open Access Journals (Sweden)

    P Roberto Bakker

    Full Text Available OBJECTIVE: The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. METHOD: Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. RESULTS: The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. CONCLUSIONS: Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.

  9. Persistent angina

    DEFF Research Database (Denmark)

    Jespersen, L.; Abildstrom, S. Z.; Hvelplund, Anders

    2013-01-01

    To evaluate persistent angina in stable angina pectoris with no obstructive coronary artery disease (CAD) compared to obstructive CAD and its relation to long-term anxiety, depression, quality of life (QOL), and physical functioning. We invited 357 patients (men = 191; women = 166; response rate 83......-obstructive CAD or normal coronary arteries than in patients with obstructive CAD. Persistent angina symptoms were associated with long-term anxiety, depression, impaired physical functioning, and QOL irrespective of the degree of CAD. Contrary to common perception, excluding obstructive CAD in stable angina does...... %) with no prior cardiovascular disease who had a first-time coronary angiography (CAG) in 2008-2009 due to suspected stable angina to participate in a questionnaire survey in 2011 with the Seattle Angina Questionnaire and the Hospital Anxiety and Depression Scale as key elements. Long-term persistent angina (i...

  10. Why Social Exclusion Persists among Older People in Australia

    Directory of Open Access Journals (Sweden)

    Riyana Miranti

    2015-07-01

    Full Text Available The existing literature on social exclusion among older people, though relatively limited, suggests that disadvantage among older people is cumulative in nature. Some aspects of disadvantage starting at early life stages have long-term consequences. As such, older people with disadvantages may be subject to higher risks of persistent social exclusion. This article aims to improve understanding of social exclusion and its persistence among senior Australians in three ways. Firstly, the incidence of social exclusion among older people is analysed using selected indicators. Secondly, the study examines whether an older person experiencing social exclusion at one time is more likely to experience it again (persistence. Thirdly, it investigates what factors may be protecting older people from social exclusion. The analysis is conducted using the first eight waves of the Household, Income and Labour Dynamics in Australia (HILDA Survey. The sample of older people is disaggregated into a younger group (55–64 years at wave 1 and an older group (65+ years. The article suggests that higher education and income, as well as better health conditions and previous employment experiences, are important protective factors from social exclusion for older Australians.

  11. Severe Tryptophan Starvation Blocks Onset of Conventional Persistence and Reduces Reactivation of Chlamydia trachomatis▿

    Science.gov (United States)

    Leonhardt, Ralf M.; Lee, Seung-Joon; Kavathas, Paula B.; Cresswell, Peter

    2007-01-01

    The intracellular survival of the bacterial pathogen Chlamydia trachomatis depends on protein synthesis by the microbe soon after internalization. Pharmacologic inhibition of bacterial translation inhibits early trafficking of the parasitophorous vacuole (inclusion) to the microtubule-organizing center (MTOC) and promotes its fusion with lysosomes, which is normally blocked by Chlamydia. Depletion of cellular tryptophan pools by gamma interferon-inducible indoleamine-2,3-dioxygenase (IDO) is believed to be the major innate immune mechanism controlling C. trachomatis infection in human cells, an action to which the bacteria can respond by converting into a nonreplicating but highly reactivatable persistent state. However, whether severe IDO-mediated tryptophan starvation can be sufficient to fully arrest the chlamydial life cycle and thereby counteract the onset of persistence is unknown. Here we demonstrate that at low exogenous tryptophan concentrations a substantial fraction of C. trachomatis bacteria fail to traffic to the MTOC or to switch into the conventional persistent state in gamma interferon-induced human cells. The organisms stay scattered in the cell periphery, do not retain infectivity, and display only low transcriptional activity. Importantly, the rate at which these aberrant Chlamydia bacteria become reactivated upon replenishment of cellular tryptophan pools is substantially lower. Thus, severe tryptophan depletion in cells with high IDO activity affects chlamydial development more rigorously than previously described. PMID:17724071

  12. Incidence and impact of painful exacerbations in a cohort with post-treatment persistent endodontic lesions.

    Science.gov (United States)

    Yu, Victoria Soo Hoon; Messer, Harold H; Yee, Robert; Shen, Liang

    2012-01-01

    Painful exacerbations of persistent periapical lesions have unknown incidence and impact on quality of life. This study examined the incidence and impact of painful exacerbations and evaluated potential predictive factors of pain associated with root-filled teeth with persistent lesions after root canal treatment. Patients from a university hospital clinic were screened to identify root-filled teeth with periapical lesions at time of treatment and not resolved at least 4 years later. A clinical and radiographic examination and questionnaire survey were conducted. Patient and treatment characteristics and details of pain experience were studied. Statistical analysis was carried out by using SPSS (version 18). One hundred twenty-seven patients with 185 persistent lesions were recruited. Median age of patients at recruitment was 56 years (range, 21-82 years). Median time since treatment was 5 years (range, 4-38 years). Overall incidence of flare-up (requiring an unscheduled dental visit) was only 5.8% 20 years after treatment. Less severe pain was more frequent, with a combined incidence of 45% pain at 20 years after treatment. Female patients (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2-6.0; P flare-up among persistent lesions was very low. A lower degree of pain was more common, but generally with minimal impact on daily activities. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. Impact of clonal competition for peptide-MHC complexes on the CD8[superscript +] T-cell repertoire selection in a persistent viral infection

    Energy Technology Data Exchange (ETDEWEB)

    Wynn, Katherine K.; Fulton, Zara; Cooper, Leanne; Silins, Sharon L.; Gras, Stephanie; Archbold, Julia K.; Tynan, Fleur E.; Miles, John J.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

    2008-04-29

    CD8{sup +} T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)-specific CD8{sup +} T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)-peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more 'featureless' landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.

  14. Occurrence and persistence of organic emerging contaminants and priority pollutants in five sewage treatment plants of Spain: Two years pilot survey monitoring

    International Nuclear Information System (INIS)

    Bueno, M.J. Martínez; Gomez, M.J.; Herrera, S.; Hernando, M.D.; Agüera, A.

    2012-01-01

    This work summarized all results obtained during almost two-years of a monitoring programme carried out in five municipal sewage treatment plants (STPs) located in the north, centre and south-east of Spain. The study evaluated the occurrence and persistence of a group of 100 organic compounds belonging to several chemical groups (pharmaceuticals, personal care products, pesticides and metabolites). The average removal efficiencies of the STPs studied varied from 20% (erythromycin) to 99% (acetaminophen). In analysed samples, we identified a large number of compounds at mean range concentrations between 7–59,495 ng/L and 5–32,720 ng/L for influent and effluent samples, respectively. This study also identified 20 of the mostly detected and persistent compounds in wastewater effluent, of which hydrochlorothiazide, atenolol, gemfibrozil, galaxolide and three metabolites (fenofibric acid, 4-AAA and 4-FAA), presented the highest average contribution percentages, in relation to the total load of contaminants for the different STPs effluent studied. Highlights: ► The results summarize two-years of a monitoring programme. ► 100 organic compounds (priority substances and emerging contaminants) were analysed. ► The removal efficiency of 5 STPs of Spain was evaluated. ► The presence of target compounds in treated wastewater was also checked. ► The most frequently drugs detected were: antibiotics< anti-inflammatories<β-blockers. - Antibiotics and analgesics/anti-inflammatories were the most frequently drugs detected, following by some β-blockers, synthetic fragrances, lipid regulators and diuretics.

  15. Persistent Neutrophilic Meningitis in an Immunocompetent Patient after Basilar Skull Fracture: Case Report

    Directory of Open Access Journals (Sweden)

    Uslan Daniel Z

    2011-05-01

    Full Text Available Abstract Background Persistent neutrophilic meningitis is an unusual form of chronic meningitis that is defined as clinical meningitis with a neutrophilic pleocytosis that persists for greater than 7 days despite empiric antimicrobial therapy. Although numerous disease processes can cause this syndrome, the majority of cases are due to opportunistic pathogens infecting immunocompromised hosts. Case Presentation A 47 year-old female presented after basilar skull fracture with persistent neutrophilic meningitis unresponsive to empiric broad-spectrum antibiotics. After more than weeks of intensive therapy, 4 hospitalizations and 3 relapses, Nocardia cyriacigeorgica was identified from cerebral spinal fluid. Induction therapy was begun with Ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX for 6 weeks followed by therapy with TMP-SMX and doxycycline for one year. The patient made a complete recovery without sequelae. Conclusions Due to the difficulty in obtaining a microbiologic diagnosis, appropriate treatment in cases of persistent neutrophilic meningitis is often delayed leading to morbidity, This case highlights a number of the unique features of Nocardia meningitis and the importance of considering Nocardia infection as a cause of persistent neutrophilic meningitis even in immunocompetent patients.

  16. Long-term persistence of oral human papillomavirus type 16: the HPV Infection in Men (HIM) study.

    Science.gov (United States)

    Pierce Campbell, Christine M; Kreimer, Aimée R; Lin, Hui-Yi; Fulp, William; O'Keefe, Michael T; Ingles, Donna J; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

    2015-03-01

    Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25-42] and were followed for a median of 44.4 months (IQR, 29.9-49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infection duration, 7.3 months; 95% confidence interval (CI), 6.4-NA)]. Of 10 prevalent infections, 9 (90.0%) persisted ≥12 months, 8 (80.0%) persisted ≥24 months, 4 (57.1%) persisted ≥36 months, and 2 (40.0%) persisted ≥48 months (median infection duration, NA). Twelve-month persistence of incident infections increased significantly with age (Ptrend = 0.028). Prevalent oral HPV16 infections in men persisted longer than newly acquired infections, and persistence appeared to increase with age. These findings may explain the high prevalence of oral HPV observed at older ages. Understanding oral HPV16 persistence will aid in the identification of men at high-risk of developing HPV-related oropharyngeal cancer. ©2015 American Association for Cancer Research.

  17. Students' Self-Determined Motivation, Emotional Intelligence and Academic Persistence: An Examination of Second Year Students at a Public and a Private Historically Black University

    Science.gov (United States)

    Watts-Martinez, Evanda Shentelle

    2015-01-01

    Self-determined Motivation, Emotional Intelligence, Persistence Attitudes, and Persistence Behaviors are non-cognitive factors that influence students' academic progression. This study examined the associations between Self-determined Motivation, EI, Persistence Attitudes, and Persistence Behaviors and the degree to which EI, as a mediating…

  18. Differences in Persistence and Graduation Rates of Hispanic Students in Texas Community Colleges: A Texas Statewide Study

    Science.gov (United States)

    Stagg, Danielle R.

    2017-01-01

    Purpose: The purpose of this journal-ready dissertation was to examine the 1-year persistence rates of Hispanic community college students in Texas for the 2007-2008 through the 2013-2014 academic years. Specifically, the relationship of the 1-year persistence rates for Hispanic students as a function of their institutional status (i.e., stayed or…

  19. The long persistence of regional entrepreneurship culture: Germany 1925 - 2005

    OpenAIRE

    Fritsch, Michael; Wyrwich, Michael

    2012-01-01

    We investigate the persistence of levels of self-employment and new business formation in different time periods and under different framework conditions. The analysis shows that high levels of regional self-employment and new business formation tend to be persistent for periods as long as 80 years and that such an entrepreneurial culture can even survive abrupt and drastic changes in the politic-economic environment. We thus conclude that regional entrepreneurship cultures do exist and that ...

  20. Expanded cellular clones carrying replication-competent HIV-1 persist, wax, and wane.

    Science.gov (United States)

    Wang, Zheng; Gurule, Evelyn E; Brennan, Timothy P; Gerold, Jeffrey M; Kwon, Kyungyoon J; Hosmane, Nina N; Kumar, Mithra R; Beg, Subul A; Capoferri, Adam A; Ray, Stuart C; Ho, Ya-Chi; Hill, Alison L; Siliciano, Janet D; Siliciano, Robert F

    2018-03-13

    The latent reservoir for HIV-1 in resting CD4 + T cells is a major barrier to cure. Several lines of evidence suggest that the latent reservoir is maintained through cellular proliferation. Analysis of this proliferative process is complicated by the fact that most infected cells carry defective proviruses. Additional complications are that stimuli that drive T cell proliferation can also induce virus production from latently infected cells and productively infected cells have a short in vivo half-life. In this ex vivo study, we show that latently infected cells containing replication-competent HIV-1 can proliferate in response to T cell receptor agonists or cytokines that are known to induce homeostatic proliferation and that this can occur without virus production. Some cells that have proliferated in response to these stimuli can survive for 7 d while retaining the ability to produce virus. This finding supports the hypothesis that both antigen-driven and cytokine-induced proliferation may contribute to the stability of the latent reservoir. Sequencing of replication-competent proviruses isolated from patients at different time points confirmed the presence of expanded clones and demonstrated that while some clones harboring replication-competent virus persist longitudinally on a scale of years, others wax and wane. A similar pattern is observed in longitudinal sampling of residual viremia in patients. The observed patterns are not consistent with a continuous, cell-autonomous, proliferative process related to the HIV-1 integration site. The fact that the latent reservoir can be maintained, in part, by cellular proliferation without viral reactivation poses challenges to cure.

  1. DAMPAK DEFISIENSI IODIUM MATERNAL PADA PERSISTENSI DISFUNGSI NEUROPSIKOLOGIS ANAK USIA 12 TAHUN (EFFECT OF MATERNAL IODINE DEFICIENCY ON THE PERSISTENCE OF NEUROLOGICAL DYSFUNCTIONS IN CHILDREN AGED 12 YEARS

    Directory of Open Access Journals (Sweden)

    Basuki Budiman

    2012-06-01

    Full Text Available ABSTRACT Study on the last effect of neuropsychologic dysfunction due to iodine deficiency during gestation is still scarce. This study is to confirm the persistence of neuropsychological dysfunctions at 12-year-old of children born from pregnant mothers with iodine deficiency in endemic iodine deficient area. The study is 13-year-cohort design. Iodine status (Total T4, TSH and UIE of pregnant mothers at initial study, neonatal (TSH and 12 year-old iodine status (fT4, TSH are performed. Neurological dysfunction of infants is examined every 6 weeks until the child age is 24 months. Neuropsychological dysfunction of children 12 years of age such as minimal brain dysfunction and psychological battery of Wechsler Intelligence Scale for Children (WISC are also administered. A screening to determine case and reference using is done using mini mental status examination (MMSE. Score MMSE of 28 or less are implemented as cases while others as reference. The relationship of neurological and cognitive dysfunction with both maternal iodine status and neurological dysfunction at 2 months of neonates age are elaborated. The persistency risk of neurological dysfunction at 12 years of age is 8% (95%ci: 1-15%. Maternal and neonatal iodine status (as indicated by TSH, T4 are the risk factors for the persistency at 12-years. However, delays of neurological development in two-month old infants are found as directly risk factors. Median Total IQ score for all participants are far lower than the lowest limit of normal range. A very significant difference (p=0.000 are found in Total IQ score between cases and references. Discrepancy analysis of IQV-IQP indicates brain lesions in subtle form, such as diadokhokinesis, praxis, memory, distractibility and lowered IQ score. Neuropsychological dysfunctions due maternal iodine deficiency are still persistence at 12 years. Maternal T4 during gestation is not only influences on the persistency but also impaires directly on the

  2. A rare case of persistent metopic suture in an elderly individual: Incidental autopsy finding with clinical implications

    Directory of Open Access Journals (Sweden)

    S Vikram

    2014-01-01

    Full Text Available Metopic suture is a dense fibrous joint extending from the nasion to the bregma. Normally, closure of this suture takes place between 1-8 years of age. Failure of this closure beyond 8 years leads to persistent metopic suture. A rare case of persistent metopic suture in a 60-year-old male is documented, who committed suicide by alleged consumption of organophosphorous compound at District Govt. Wenlock Hospital, Mangalore, Karnataka, India. Metopic suture may mimic skull fracture and may mislead an inexperienced forensic expert. Neurosurgeon should also be aware of this anatomical variation while performing frontal craniotomy, as the persistent metopic suture may mimic vertical fracture of the skull. Hence, in this case report, the clinical and medico-legal implications of the persistent metopic sutures have been discussed.

  3. Treatment of persistent knee synovitis with Yttrium 90

    International Nuclear Information System (INIS)

    Bouyoucef, S.E.

    2007-01-01

    Full text: Management of persistent knee synovitis includes both systemic and local articular treatment relevant to specific etiology. Local treatment may involve attempts to control inflammation and pain in knee joints by intra articular application of analgesics or glucocorticoids. However, in many patients these fail to reduce significantly the synovitis phenomenon and moreover they may lead to severe side effects. Radiosynoviorthesis with Y90 has been in use for many years in several joint pathologies. Indications of Radiosynoviorthesis include various inflammatory and degenerative diseases and its use should be envisaged when other conservative methods have failed like intra articular injections of long acting corticosteroids. Persistent knee synovitis is defined by the presence of hydrops in the joint or functional impairment with warmth, pain and local signs and symptoms requiring intra articular injection of glucocorticoids. In this study, 151 knees with persistent knee synovitis have been treated with Y 90 and have had all a minimum of one year follow up. Many parameters have been identified to measure efficiency of the RSO including pain, hydarthrosis, mobility, as well as global perception of the patients. Excellent and good responses have been appreciated through pain at rest, pain at stress, volume of effusion, and articular mobility. Results showed that percentage of excellent and good response is superior to 80% at three and six months. Success of Y 90 appears to be higher for rheumatoid arthritis as well as for oligoarthritis. Whatever the etiology, intensity of the inflammatory process appears one the major parameters which could better predict the outcomes of yttrium 90 in persistent knee synovitis. (author)

  4. Hydrocephalus in mice following X-irradiation at early gestational stage. Possibly due to persistent deceleration of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Aolad, H.M.; Inouye, Minoru; Darmanto, W.; Hayasaka, Shizu; Murata, Yoshiharu [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    2000-09-01

    The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telecephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus. (author)

  5. Hydrocephalus in mice following X-irradiation at early gestational stage. Possibly due to persistent deceleration of cell proliferation

    International Nuclear Information System (INIS)

    Aolad, H.M.; Inouye, Minoru; Darmanto, W.; Hayasaka, Shizu; Murata, Yoshiharu

    2000-01-01

    The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telecephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus. (author)

  6. Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient.

    Directory of Open Access Journals (Sweden)

    Steven A Yukl

    Full Text Available There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV DNA or RNA was detected in peripheral blood mononuclear cells (PBMC, spinal fluid, lymph node, or terminal ileum, and no replication-competent virus could be cultured from PBMCs. However, HIV RNA was detected in plasma (2 laboratories and HIV DNA was detected in the rectum (1 laboratory at levels considerably lower than those expected in ART-suppressed patients. It was not possible to obtain sequence data from plasma or gut, while an X4 sequence from PBMC did not match the pre-transplant sequence. HIV antibody levels were readily detectable but declined over time; T cell responses were largely absent. The occasional, low-level PCR signals raise the possibility that some HIV nucleic acid might persist, although they could also be false positives. Since HIV levels in well-treated individuals are near the limits of detection of current assays, more sensitive assays need to be developed and validated. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure.

  7. Overweight in Infancy : Which Pre- and Perinatal Factors Determine Overweight Persistence or Reduction? A Birth Cohort Followed for 11 Years

    NARCIS (Netherlands)

    van Rossem, Lenie; Wijga, Alet H.; Brunekreef, Bert; de Jongste, Johan C.; Kerkhof, Marjan; Postma, Dirkje S.; Gehring, Ulrike; Smit, Henriette A.

    2014-01-01

    Background: A considerable proportion of children with early-life overweight attain a normal weight. To recognize infants at risk of persistent overweight, we compared early-life factors of children with a longitudinal pattern of persistent overweight to children with a pattern of overweight in

  8. Overweight in infancy: which pre- and perinatal factors determine overweight persistence or reduction? A birth cohort followed for 11 years

    NARCIS (Netherlands)

    van Rossem, Lenie; Wijga, Alet H; Brunekreef, Bert; de Jongste, Johan C; Kerkhof, Marjan; Postma, Dirkje S; Gehring, Ulrike; Smit, Henriëtte A

    2014-01-01

    BACKGROUND: A considerable proportion of children with early-life overweight attain a normal weight. To recognize infants at risk of persistent overweight, we compared early-life factors of children with a longitudinal pattern of persistent overweight to children with a pattern of overweight in

  9. Prevalence, incidence rates and persistence of contact allergy and allergic contact dermatitis in The Odense Adolescence Cohort Study: a 15-year follow-up

    DEFF Research Database (Denmark)

    Mortz, C. G.; Bindslev-Jensen, C.; Andersen, Klaus Ejner

    2013-01-01

    BACKGROUND: A cohort of 1501 unselected 8th grade schoolchildren was established 15 years ago with the aim to follow the course of contact allergy and allergic contact dermatitis (ACD) from school age into adult life. To date no studies have evaluated incidence rates and persistence of contact al...... the most common contact allergen, and new sensitizations occurred despite the European Union nickel regulation. Fragrance mix I was a poor marker for history of eczematous skin reaction to perfumed products....

  10. Migration and persistence of human influenza A viruses, Vietnam, 2001-2008.

    Science.gov (United States)

    Le, Mai Quynh; Lam, Ha Minh; Cuong, Vuong Duc; Lam, Tommy Tsan-Yuk; Halpin, Rebecca A; Wentworth, David E; Hien, Nguyen Tran; Thanh, Le Thi; Phuong, Hoang Vu Mai; Horby, Peter; Boni, Maciej F

    2013-11-01

    Understanding global influenza migration and persistence is crucial for vaccine strain selection. Using 240 new human influenza A virus whole genomes collected in Vietnam during 2001-2008, we looked for persistence patterns and migratory connections between Vietnam and other countries. We found that viruses in Vietnam migrate to and from China, Hong Kong, Taiwan, Cambodia, Japan, South Korea, and the United States. We attempted to reduce geographic bias by generating phylogenies subsampled at the year and country levels. However, migration events in these phylogenies were still driven by the presence or absence of sequence data, indicating that an epidemiologic study design that controls for prevalence is required for robust migration analysis. With whole-genome data, most migration events are not detectable from the phylogeny of the hemagglutinin segment alone, although general migratory relationships between Vietnam and other countries are visible in the hemagglutinin phylogeny. It is possible that virus lineages in Vietnam persisted for >1 year.

  11. Persistent post-stroke dysphagia treated with cricopharyngeal myotomy

    Directory of Open Access Journals (Sweden)

    Sruthi S Nair

    2016-01-01

    Full Text Available Post-stroke dysphagia is a common problem after stroke. About 8-13% patients have persistent dysphagia and are unable to return to pre-stroke diet even after 6 months of stroke. Use of percutaneous endoscopic gastrostomy (PEG may be required in these patients, which may be psychologically unacceptable and impair the quality of life. In those with cricopharyngeal dysfunction leading on to refractory post-stroke dysphagia, cricopharyngeal myotomy and injection of botulinum toxin are the treatment options. We present a case of vertebrobasilar stroke who had persistent dysphagia due to cricopharyngeal dysfunction with good recovery of swallowing function following cricopharyngeal myotomy 1.5 years after the stroke.

  12. Persistent ectopic pregnancy after milking procedure: Case report

    Directory of Open Access Journals (Sweden)

    Semra Kayataş

    2014-03-01

    Full Text Available Ectopic pregnancy is the settlement of the pregnancy product at any site other than the endometrium. The incidence of ectopic pregnancy have increased in the last 20 years. Increased frequency and early diagnosis has led to conservative treatment methods to become more favorable. Follow-up, medical management and surgical managements are considered as conservative methods. As salpingostomy is the most common conservative surgical method, milking is considered as an alternative conservative surgical method. The most important complication of the conservative surgery is the persistence of ectopic pregnancy because of the residual trophoblastic tissue. Since the prediction of the persistent ectopic pregnancy is difficult after the conservative surgery, β-HCG follow up is so important for early diagnosis. In this case report we have discussed the case of the patient who admitted to our clinic with persistent ectopic pregnancy with acute abdomen, after the treatment with milking procedure whom than treated by salpingectomy procedure.

  13. [Persistence of the primordial vitreous body and buphthalmos].

    Science.gov (United States)

    Cernea, P; Simionescu, C; Bosun, I

    1995-01-01

    Persistence of the hyperplasic primordial vitreous body is determined by a deletion of embryonal development of the vitreous body and of the hyaloid vascular system. Infant aged 3.5 years presents persistence of primordial vitreous body with crystalline dislocation in the camera aquosa and secondary buphthalmos of the left eye and microphthalmos with dislocation of the crystalline in the vitreous body of the right eye. At the back of the right eye we noticed a whitish mass, richly vascularized with vestiges from the hyaloid artery, but the posterior half of the vitreous cavity is filled with microscopic blood; the fibrovascular membrane is made of conjunctive tissue set in parallel layers and vessels with macrolipophagic degeneration. Microscopic investigation of retina reveals glial hyperplasia zones in the neighbourhood of the vitreous body. In the present paper the authors show the persistence of the primordial vitreous body in the left eye and bilateral dislocation of the crystalline, revealing multiple ocular malformations.

  14. Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Paul Fineran

    2016-11-01

    Full Text Available Background. Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC, a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC. Methods. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed. Results. Macrophages infected with persistent intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that persistent intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were

  15. Differential wolf-pack-size persistence and the role of risk when hunting dangerous prey

    Science.gov (United States)

    Barber-Meyer, Shannon M.; Mech, L. David; Newton, Wesley E.; Borg, Bridget

    2016-01-01

    Risk to predators hunting dangerous prey is an emerging area of research and could account for possible persistent differences in gray wolf (Canis lupus) pack sizes. We documented significant differences in long-term wolf-pack-size averages and variation in the Superior National Forest (SNF), Denali National Park and Preserve, Yellowstone National Park, and Yukon, Canada (pwolves’ risk when hunting primary prey, for those packs (N=3) hunting moose (Alces americanus) were significantly larger than those (N=10) hunting white-tailed deer (Odocoileus virginianus) (F1,8=16.50, p=0.004). Our data support the hypothesis that differential pack-size persistence may be perpetuated by differences in primary prey riskiness to wolves, and we highlight two important extensions of this idea: (1) the potential for wolves to provision and defend injured packmates from other wolves and (2) the importance of less-risky, buffer prey to pack-size persistence and year-to-year variation. Risk to predators hunting dangerous prey is an emerging area of research and could account for possible persistent differences in gray wolf (Canis lupus) pack sizes. We documented significant differences in long-term wolf-pack-size averages and variation in the Superior National Forest (SNF), Denali National Park and Preserve, Yellowstone National Park, and Yukon, Canada (pwolves’ risk when hunting primary prey, for those packs (N=3) hunting moose (Alces americanus) were significantly larger than those (N=10) hunting white-tailed deer (Odocoileus virginianus) (F1,8=16.50, p=0.004). Our data support the hypothesis that differential pack-size persistence may be perpetuated by differences in primary prey riskiness to wolves, and we highlight two important extensions of this idea: (1) the potential for wolves to provision and defend injured packmates from other wolves and (2) the importance of less-risky, buffer prey to pack-size persistence and year-to-year variation.

  16. A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells.

    Science.gov (United States)

    Xiao, Hui; Bid, Hemant Kumar; Jou, David; Wu, Xiaojuan; Yu, Wenying; Li, Chenglong; Houghton, Peter J; Lin, Jiayuh

    2015-02-06

    Signal transducers and activators of transcription 3 (STAT3) signaling is persistently activated and could contribute to tumorigenesis of medulloblastoma. Numerous studies have demonstrated that inhibition of the persistent STAT3 signaling pathway results in decreased proliferation and increased apoptosis in human cancer cells, indicating that STAT3 is a viable molecular target for cancer therapy. In this study, we investigated a novel non-peptide, cell-permeable small molecule, named LY5, to target STAT3 in medulloblastoma cells. LY5 inhibited persistent STAT3 phosphorylation and induced apoptosis in human medulloblastoma cell lines expressing constitutive STAT3 phosphorylation. The inhibition of STAT3 signaling by LY5 was confirmed by down-regulating the expression of the downstream targets of STAT3, including cyclin D1, bcl-XL, survivin, and micro-RNA-21. LY5 also inhibited the induction of STAT3 phosphorylation by interleukin-6 (IL-6), insulin-like growth factor (IGF)-1, IGF-2, and leukemia inhibitory factor in medulloblastoma cells, but did not inhibit STAT1 and STAT5 phosphorylation stimulated by interferon-γ (IFN-γ) and EGF, respectively. In addition, LY5 blocked the STAT3 nuclear localization induced by IL-6, but did not block STAT1 and STAT5 nuclear translocation mediated by IFN-γ and EGF, respectively. A combination of LY5 with cisplatin or x-ray radiation also showed more potent effects than single treatment alone in the inhibition of cell viability in human medulloblastoma cells. Furthermore, LY5 demonstrated a potent inhibitory activity on cell migration and angiogenesis. Taken together, these findings indicate LY5 inhibits persistent and inducible STAT3 phosphorylation and suggest that LY5 is a promising therapeutic drug candidate for medulloblastoma by inhibiting persistent STAT3 signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Two regulatory RNA elements affect TisB-dependent depolarization and persister formation.

    Science.gov (United States)

    Berghoff, Bork A; Hoekzema, Mirthe; Aulbach, Lena; Wagner, E Gerhart H

    2017-03-01

    Bacterial survival strategies involve phenotypic diversity which is generated by regulatory factors and noisy expression of effector proteins. The question of how bacteria exploit regulatory RNAs to make decisions between phenotypes is central to a general understanding of these universal regulators. We investigated the TisB/IstR-1 toxin-antitoxin system of Escherichia coli to appreciate the role of the RNA antitoxin IstR-1 in TisB-dependent depolarization of the inner membrane and persister formation. Persisters are phenotypic variants that have become transiently drug-tolerant by arresting growth. The RNA antitoxin IstR-1 sets a threshold for TisB-dependent depolarization under DNA-damaging conditions, resulting in two sub-populations: polarized and depolarized cells. Furthermore, our data indicate that an inhibitory 5' UTR structure in the tisB mRNA serves as a regulatory RNA element that delays TisB translation to avoid inappropriate depolarization when DNA damage is low. Investigation of the persister sub-population further revealed that both regulatory RNA elements affect persister levels as well as persistence time. This work provides an intriguing example of how bacteria exploit regulatory RNAs to control phenotypic heterogeneity. © 2016 John Wiley & Sons Ltd.

  18. Persistency of atmospheric diffusion conditions in Angra dos Reis - Brazil

    International Nuclear Information System (INIS)

    Nicolli, D.

    1981-12-01

    Based on a 2 year observation period, the diffusion conditions at the Almirante Alvaro Alberto N.P.P. site, in Angra dos Reis, are analized with respect to persistency as a function of the wind direction, the Pasquill stability class and the time of the day. The Pasquill stability class relates to the bulk vertical temperature gradient measured between 2m and 50m in the atmosphere; the wind direction is measured at 50m height. The persistency is defined in this report as the probability that the wind direction will remain longer than a given time in a sector without change in the diffusion category by more than a certain stage. During the day the persistency is mostly affected by the sea breeze with predominance of the unstable and neutral categories. At night the stable categories dominate. The alternating sea and land breezes disturb daily the trade wind field resulting in low persistency of the diffusion conditions. (Author) [pt

  19. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines.

    Science.gov (United States)

    Salik, Elaha; Løvik, Ida; Andersen, Klaus E; Bygum, Anette

    2016-11-02

    There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons. Two patients had skin biopsies performed from their skin lesions, and 2 patients had the nodules surgically removed. Forty-two children had a patch-test performed with 2% aluminium chloride hexahydrate in petrolatum and 39 of them (92%) had a positive reaction. The persistent skin reactions were treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations.

  20. Preface to the SPECIAL ISSUE: Excitonic Solar Cells(II)

    Institute of Scientific and Technical Information of China (English)

    Jianjun Tian; Meicheng Li; Kaibo Zheng

    2016-01-01

    Among all the excitonic solar cells(ESCs)including dyesensitized solar cells(DSSCs),quantum solar cells(QDSCs),perovskites solar cells(PSCs),and organic photovoltaics(OPVs),PSCs attracted enormous research attention in the past 7 years and attained the highest power conversion efficiency(PCE)of over 20%with the biggest progress,from 3.8%to over 22.1%in 7 years.However,one can easily realize the fact that such a rapid progress achieved in PSCs was made possible is largely based on the fundamental knowledge,experimental skills,and characterization facilities obtained and accumulated through the multi-decade long endeavor in the study of other excitonic solar cells.Even though PSCs have attractedmuch research human resource and funding,the study on other excitonic solar cells has never stopped,and such persistent efforts

  1. Persistent Identifiers for Dutch cultural heritage institutions

    Science.gov (United States)

    Ras, Marcel; Kruithof, Gijsbert

    2016-04-01

    Over the past years, more and more collections belonging to archives, libraries, media, museums, and knowledge institutes are being digitised and made available online. These are exciting times for ALM institutions. They are realising that, in the information society, their collections are goldmines. Unfortunately most heritage institutions in the Netherlands do not yet meet the basic preconditions for long-term availability of their collections. The digital objects often have no long lasting fixed reference yet. URL's and web addresses change. Some digital objects that were referenced in Europeana and other portals can no longer be found. References in scientific articles have a very short life span, which is damaging for scholarly research. In 2015, the Dutch Digital Heritage Network (NDE) has started a two-year work program to co-ordinate existing initiatives in order to improve the (long-term) accessibility of the Dutch digital heritage for a wide range of users, anytime, anyplace. The Digital Heritage Network is a partnership established on the initiative of the Ministry of Education, Culture and Science. The members of the NDE are large, national institutions that strive to professionally preserve and manage digital data, e.g. the National Library, The Netherlands Institute for Sound and Vision, the Netherlands Cultural Heritage Agency, the Royal Netherlands Academy of Arts and Sciences, the National Archive of the Netherlands and the DEN Foundation, and a growing number of associations and individuals both within and outside the heritage sector. By means of three work programmes the goals of the Network should be accomplished and improve the visibility, the usability and the sustainability of digital heritage. Each programme contains of a set of projects. Within the sustainability program a project on creating a model for persistent identifiers is taking place. The main goals of the project are (1) raise awareness among cultural heritage institutions on the

  2. [Hydrocholecystis, unrecognized cause of painful abdominal crises in patients with sickle cell anemia].

    Science.gov (United States)

    Cabrol, S; Desjardin, F; Baruchel, S; Bégué, P; Cordier, M D; Lasfargues, G

    1985-12-01

    The first case of painful abdominal crisis caused by hydrops of the gallbladder during sickle cell disease is reported. The cholecystosonography allowed diagnosis and supervision in a 4 year-old black boy with sickle cell anemia. The persistence of hydrops led to cholecystectomy. Pathophysiology is discussed according to the other etiologies reported in the literature.

  3. Persistence of experimental Rocio virus infection in the golden hamster (Mesocricetus auratus

    Directory of Open Access Journals (Sweden)

    Daniele Freitas Henriques

    2012-08-01

    Full Text Available Rocio virus (ROCV is an encephalitic flavivirus endemic to Brazil. Experimental flavivirus infections have previously demonstrated a persistent infection and, in this study, we investigated the persistence of ROCV infection in golden hamsters (Mesocricetus auratus. The hamsters were infected intraperitoneally with 9.8 LD50/0.02 mL of ROCV and later anaesthetised and sacrificed at various time points over a 120-day period to collect of blood, urine and organ samples. The viral titres were quantified by real-time-polymerase chain reaction (qRT-PCR. The specimens were used to infect Vero cells and ROCV antigens in the cells were detected by immunefluorescence assay. The levels of antibodies were determined by the haemagglutination inhibition technique. A histopathological examination was performed on the tissues by staining with haematoxylin-eosin and detecting viral antigens by immunohistochemistry (IHC. ROCV induced a strong immune response and was pathogenic in hamsters through neuroinvasion. ROCV was recovered from Vero cells exposed to samples from the viscera, brain, blood, serum and urine and was detected by qRT-PCR in the brain, liver and blood for three months after infection. ROCV induced histopathological changes and the expression of viral antigens, which were detected by IHC in the liver, kidney, lung and brain up to four months after infection. These findings show that ROCV is pathogenic to golden hamsters and has the capacity to cause persistent infection in animals after intraperitoneal infection.

  4. Medication persistence with long-term, specific grass pollen immunotherapy measured by prescription renewal rates.

    Science.gov (United States)

    Sieber, J; De Geest, S; Shah-Hosseini, K; Mösges, R

    2011-04-01

    We assessed medication persistence using prescription renewal rates for grass pollen specific immunotherapy (SIT) in a representative population of patients in Germany to evaluate whether the perception of superior persistence for the subcutaneous route compared to the sublingual route could be confirmed in clinical practice. Individual prescriptions for allergen immunotherapy were extracted from a national prescription database (INSIGHT Health) and followed over 3 years on a per-patient basis. However, patients' medical history and treatment schedules were not available for analysis. Products were identified by the national drug code (PZN number) and grouped to either subcutaneous immunotherapy (SCIT) with natural extract injections, SCIT with modified allergens (allergoids) or sublingual immunotherapy (SLIT) with natural pollen extract solutions. Persistence was defined as at least one prescription of the individual drug in the respective years. A total of 1409 patients started SIT in 2005 (112, 695, and 602 for natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively). In 2006, 71%, 55%, and 59% of those patients had at least one renewal prescription of natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively, as well as 51%, 34%, and 39% in 2007. In both years, persistence with natural extract SLIT was significantly higher than with natural extract SCIT (p = 0.0015 for 2006, p = 0.0003 for 2007) and allergoid SCIT (p = 0.0152 for 2006, p = 0.0111 for 2007). There were no significant differences between the two SCIT groups. Medication persistence with grass pollen SIT in a representative sample of patients in Germany was similar to published medication persistence in asthma and COPD patients. The sublingual application route shows significantly better persistency than the subcutaneous route with native allergens or allergoids.

  5. The risk for persistent adult alcohol and nicotine dependence: the role of childhood maltreatment.

    Science.gov (United States)

    Elliott, Jennifer C; Stohl, Malka; Wall, Melanie M; Keyes, Katherine M; Goodwin, Renee D; Skodol, Andrew E; Krueger, Robert F; Grant, Bridget F; Hasin, Deborah S

    2014-05-01

    Alcohol and nicotine dependence are associated with considerable morbidity and mortality, especially when cases are persistent. The risk for alcohol and nicotine dependence is increased by childhood maltreatment. However, the influence of childhood maltreatment on dependence course is unknown, and is evaluated in the current study. Physical, sexual and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over 3 years of follow-up, with and without control for other childhood adversities. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n = 1172) and nicotine dependence (n = 4017). Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measures of alcohol/nicotine dependence, childhood maltreatment and other adverse childhood experiences (e.g. parental divorce). Controlling for demographics only, physical, sexual and emotional abuse and physical neglect predicted 3-year persistence of alcohol dependence [adjusted odds ratio (AOR) = 1.50-2.99; 95% CI = 1.04-4.68] and nicotine dependence (AOR = 1.37-1.74; 95% CI = 1.13-2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AOR = 1.53-3.02; 95% CI = 1.07-4.71) and nicotine persistence (AOR = 1.35-1.72; 95% CI = 1.11-2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AOR = 1.19-1.36; 95% CI = 1.11-1.56). A history of childhood maltreatment predicts persistent adult alcohol and nicotine dependence. This association, robust to control for other childhood adversities, suggests that maltreatment (rather than a generally difficult childhood) affects the course of dependence. © 2014 Society for the Study of Addiction.

  6. Eleven-Year Retrospective Report of Super-Selective Venous Sampling for the Evaluation of Recurrent or Persistent Hyperparathyroidism in 32 Patients.

    Science.gov (United States)

    Habibollahi, Peiman; Shin, Benjamin; Shamchi, Sara P; Wachtel, Heather; Fraker, Douglas L; Trerotola, Scott O

    2018-01-01

    Parathyroid venous sampling (PAVS) is usually reserved for patients with persistent or recurrent hyperparathyroidism after parathyroidectomy with inconclusive noninvasive imaging studies. A retrospective study was performed to evaluate the diagnostic efficacy of super-selective PAVS (SSVS) in patients needing revision neck surgery with inconclusive imaging. Patients undergoing PAVS between 2005 and 2016 due to persistent or recurrent hyperparathyroidism following surgery were reviewed. PAVS was performed in all patients using super-selective technique. Single-value measurements within central neck veins performed as part of super-selective PAVS were used to simulate selective venous sampling (SVS) and allow for comparison to data, which might be obtained in a non-super-selective approach. 32 patients (mean age 51 ± 15 years; 8 men and 24 women) met inclusion and exclusion criteria. The sensitivity and positive predictive value (PPV) of SSVS for localizing the source of elevated PTH to a limited area in the neck or chest was 96 and 84%, respectively. Simulated SVS, on the other hand, had a sensitivity of 28% and a PPV of 89% based on the predefined gold standard. SSVS had a significantly higher sensitivity compared to simulated SVS (p localizing the source of hyperparathyroidism in patients undergoing revision surgery for hyperparathyroidism in whom noninvasive imaging studies are inconclusive. SSVS data had also markedly higher sensitivity for localizing disease in these patients compared to simulated SVS.

  7. Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

    Science.gov (United States)

    Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua

    2017-02-15

    Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised

  8. Successful treatment of persistent bronchorrhea by gefitinib in a case with Recurrent Bronchioloalveolar Carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Shimono Takatsugu

    2003-07-01

    Full Text Available Abstract Background Bronchorrhea is one of late complaints in patients with bronchioloalveolar carcinoma (BAC and hampers their quality of life. Although an effective treatment for bronchorrhea in these patients has not been established, recently we have treated effectively one case of persistent bronchorrhea associated with clinical recurrent BAC with gefitinib (ZD1839, 'Iressa™'; AstraZeneca Japan; Osaka, Japan. Case Presentation A 63-year-old Japanese female had undergone left pneumonectomy with radical lymph node dissection (ND2a for diffuse type bronchioloalveolar carcinoma originated in left lower lobe. Multiple pulmonary metastases in right lung were found one year after operation. Pulmonary metastatic lesion has grown and she complained of progressive symptoms of massive watery sputum and dyspnea, four years after operation. Although her symptom was getting worse in spite of routine treatment, it completely disappeared within 2 weeks of starting oral gefitinib. Thereafter, she has been symptom-free and shows good partial response on repeat scan after 9 months of oral gefitinib. Conclusions The dramatic remission of persistent bronchorrhea by gefitinib in the presented case suggests that gefitinib might be a promising option for bronchioloalveolar carcinoma, particularly in cases with severe bronchorrhea. Although it is not possible to comment on whether the improvement came from tumor cell death itself or suppressive effect of mucin synthesis by the epidermal growth factor receptor-tyrosine kinase inhibitory action.

  9. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

    Science.gov (United States)

    Kiel, Menno A; Röder, Esther; Gerth van Wijk, Roy; Al, Maiwenn J; Hop, Wim C J; Rutten-van Mölken, Maureen P M H

    2013-08-01

    Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent. Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  10. Single-Dose Universal Hepatitis A Immunization in Argentina: Low Viral Circulation and High Persistence of Protective Antibodies Up to 4 Years.

    Science.gov (United States)

    Vizzotti, C; González, J; Rearte, A; Urueña, A; Pérez Carrega, M; Calli, R; Gentile, A; Uboldi, A; Ramonet, M; Cañero-Velasco, M; Diosque, M

    2015-12-01

    Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children aged 12 months in 2005. Between 2005 and 2011, a dramatic decline was observed in HAV infection rates, fulminant hepatitis, and liver transplantation. This study assessed current viral circulation and estimated protective antibody persistence 4 years after vaccination. Prevalence of prevaccination anti-HAV antibodies in 12-month-old children was evaluated as an indirect estimation of viral circulation (Group A). Seroprevalence was also measured in 5-year-old children who received 1 dose of HAV vaccine at 1 year of age (Group B). Blood samples were tested for immunoglobulin (Ig)G anti-HAV antibodies (seroprotection = ≥10 mIU/mL). All Group A-positive samples were tested for IgM anti-HAV antibodies to identify recent infections. Logistic regression analysis was done to evaluate associations between demographic and socioeconomic variables and seroprotection. Of 433 children from Group A, 29.5% (95% confidence interval [CI], 25.2-33.8) were positive for IgG anti-HAV antibodies with a geometric mean concentration (GMC) of 6.17 mIU/mL (95% CI, 5.33-7.15 mIU/mL); all IgM anti-HAV were negative. From 1139 in Group B, 93% (95% CI, 91.7-94.6) maintained seroprotection with a GMC of 97.96 mIU/mL (95% CI, 89.21-107.57 mIU/mL). Kindergarten attendance was associated with seroprotection in Group B (odds ratio [OR], 2.0; 95% CI, 1.26-3.3). In contrast, high maternal educational level was associated with a lack of seroprotection in this group (OR, .26; 95% CI, .09-.8). Single-dose, universal hepatitis A immunization in infants resulted in low HAV circulation and persistent immunologic protection up to 4 years in Argentina. Variables associated with presence or absence of seroprotection in vaccinated children could be related to differences in hygiene habits in settings with residual viral circulation. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric

  11. Children's white blood cell counts in relation to developmental exposures to methylmercury and persistent organic pollutants

    DEFF Research Database (Denmark)

    Oulhote, Youssef; Shamim, Z; Kielsen, Katrine

    2017-01-01

    ), and total mercury (Hg) were measured in maternal (n = 56) and children's blood at 18 months (n = 42) and 5 years (n = 54). We constructed latent functions for exposures at three different ages using factor analyses and applied structural equation models adjusted for covariates. Results Prenatal mercury....... In contrast, the 5-year PFASs concentrations were associated with higher basophil counts (B = 46% SD, 95% CI: 13, 79). Significantly reduced subpopulations of lymphocytes such as B cells, CD4-positive T helper cells and CD4 positive recent thymic emigrants may suggest cellular immunity effects...... and dysregulation of T-cell mediated immunity. Conclusion Developmental exposure to environmental immunotoxicants appears to have different impacts on WBC counts in childhood....

  12. A Pediatric Case of Systemic Lupus Erythematosus Developed 10 Years after Cord Blood Transplantation for Juvenile Myelomonocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Masayuki Nagasawa

    2012-01-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (allo-HSCT is a most powerful immunotherapy for hematological malignancies. However, the impact of immunological disturbances as a result of allo-HSCT is not understood well. We experienced an 11-year-old boy who presented with systemic lupus erythemathosus (SLE 10 years after unrelated cord blood transplantation of male origin for juvenile myelomonocytic leukemia (JMML with monosomy 7. Bone marrow examination showed complete remission without monosomy 7. Genetic analysis of peripheral blood revealed mixed chimera with recipient cells consisting of <5% of T cells, 50–60% of B cells, 60–75% of NK cells, 70–80% of macrophages, and 50–60% of granulocytes. Significance of persistent mixed chimera as a cause of SLE is discussed.

  13. Is adipose tissue a place for Mycobacterium tuberculosis persistence?

    Directory of Open Access Journals (Sweden)

    Olivier Neyrolles

    Full Text Available BACKGROUND: Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB, has the ability to persist in its human host for exceptionally long periods of time. However, little is known about the location of the bacilli in latently infected individuals. Long-term mycobacterial persistence in the lungs has been reported, but this may not sufficiently account for strictly extra-pulmonary TB, which represents 10-15% of the reactivation cases. METHODOLOGY/PRINCIPAL FINDINGS: We applied in situ and conventional PCR to sections of adipose tissue samples of various anatomical origins from 19 individuals from Mexico and 20 from France who had died from causes other than TB. M. tuberculosis DNA could be detected by either or both techniques in fat tissue surrounding the kidneys, the stomach, the lymph nodes, the heart and the skin in 9/57 Mexican samples (6/19 individuals, and in 8/26 French samples (6/20 individuals. In addition, mycobacteria could be immuno-detected in perinodal adipose tissue of 1 out of 3 biopsy samples from individuals with active TB. In vitro, using a combination of adipose cell models, including the widely used murine adipose cell line 3T3-L1, as well as primary human adipocytes, we show that after binding to scavenger receptors, M. tuberculosis can enter within adipocytes, where it accumulates intracytoplasmic lipid inclusions and survives in a non-replicating state that is insensitive to the major anti-mycobacterial drug isoniazid. CONCLUSIONS/SIGNIFICANCE: Given the abundance and the wide distribution of the adipose tissue throughout the body, our results suggest that this tissue, among others, might constitute a vast reservoir where the tubercle bacillus could persist for long periods of time, and avoid both killing by antimicrobials and recognition by the host immune system. In addition, M. tuberculosis-infected adipocytes might provide a new model to investigate dormancy and to evaluate new drugs for the treatment of

  14. PERSISTENCE AND ACADEMIC ACHIEVEMENT IN FOREIGN LANGUAGE IN NATURAL SCIENCES STUDENTS

    Directory of Open Access Journals (Sweden)

    Alexandr I Krupnov

    2017-12-01

    Full Text Available The article discusses the results of empirical study of the association between variables of persistence and academic achievement in foreign languages. The sample includes students of the Faculty of Physics, Mathematics and Natural Science at the RUDN University ( n = 115, divided into 5 subsamples, two of which are featured in the present study (the most and the least successful students subsamples. Persistence as a personality trait is studied within A.I. Krupnov’s system-functional approach. A.I. Krupnov’s paper-and-pencil test was used to measure persistence variables. Academic achievement was measured according to the four parameters: Phonetics, Grammar, Speaking and Political vocabulary based on the grades students received during the academic year. The analysis revealed that persistence displays different associations with academic achievement variables in more and less successful students subsamples, the general prominence of this trait is more important for unsuccessful students. Phonetics is the academic achievement variable most associated with persistence due to its nature, a skill one can acquire through hard work and practice which is the definition of persistence. Grammar as an academic achievement variable is not associated with persistence and probably relates to other factors. Unsuccessful students may have difficulties in separating various aspects of language acquisition from each other which should be taken into consideration by the teachers.

  15. Inflation persistence and flexible prices

    OpenAIRE

    Robert Dittmar; William T. Gavin; Finn E. Kydland

    2004-01-01

    If the central bank follows an interest rate rule, then inflation is likely to be persistence, even when prices are fully flexible. Any shock, whether persistent or not, may lead to inflation persistence. In equilibrium, the dynamics of inflation are determined by the evolution of the spread between the real interest rate and the central bank’s target. Inflation persistence in U.S. data can be characterized by a vector autocorrelation function relating inflation and deviations of output from ...

  16. Surviving colorectal cancer: long-term, persistent ostomy-specific concerns and adaptations.

    Science.gov (United States)

    Sun, Virginia; Grant, Marcia; McMullen, Carmit K; Altschuler, Andrea; Mohler, M Jane; Hornbrook, Mark C; Herrinton, Lisa J; Baldwin, Carol M; Krouse, Robert S

    2013-01-01

    The purpose of this article was to describe persistent ostomy-specific concerns and adaptations in long-term (>5 years) colorectal cancer survivors with ostomies. Thirty-three colorectal cancer survivors who participated in 8 gender- and health-related quality of life stratified focus groups and 130 colorectal cancer survivors who provided written comments to 2 open-ended questions on ostomy location and pouch problems participated in the study. Data were collected on health maintenance organization members in Oregon, southwestern Washington, and northern California. Qualitative data were analyzed for the 8 focus groups and written comments from 2 open-ended survey questions. Discussions from the focu s groups were recorded, transcribed, and analyzed using content analysis. Written content from the open-ended questions was derived from a mailed questionnaire on health-related quality of life in survivors with ostomies and analyzed using content analysis. Discussions related to persistent ostomy-related issues more than 5 years after formation were common. Persistent ostomy-related issues were focused on clothing restrictions and adaptations, dietary concerns, issues related to ostomy equipment and self-care, and the constant need to find solutions to adjust and readjust to living with an ostomy. Ostomy-specific concerns persist 5 years and more for long-term colorectal cancer survivors after initial ostomy formation. Adaptations tend to be individualized and based on trial and error. Findings underscore the need to develop long-term support mechanisms that survivors can access to promote better coping and adjustment to living with an ostomy.

  17. Bioindicator demonstrates high persistence of sulfentrazone in dry soil

    Directory of Open Access Journals (Sweden)

    Renato Coradello Lourenço

    2015-09-01

    Full Text Available In sugarcane crop areas, the application of preemergence herbicides with long residual effect in the soil has been frequently necessary. The herbicide persistence in the soil must be high especially because of applications during the dry season of the year, after sugarcane harvest. This study aimed at estimating the sulfentrazone persistence and dissipation in dry soil using bioindicator. Five experiments were carried out, divided into two phases. In the first phase, three dose-response curves were adjusted to select the best bioindicator to be adopted in the second phase. Niger was adopted due to its lower sensibility to sulfentrazone. In the second phase, a new dose-response curve was carried out, with six doses of sulfentrazone, in order to standardize the bioindicator sensibility to sulfentrazone. At the end, another experiment with six periods of sulfentrazone persistence in dry clay soil was developed. Persistence periods were: 182, 154, 125, 98 and 30 days. The bioindicator was seeded at the application day in treated plots and control. In this experiment, the sulfentrazone dose applied was 800 g ha-1. Niger was considered a good species to estimate the sulfentrazone persistence in dry soil. The sulfentrazone phytotoxic activity was identified up to 182 days after application, and its average dissipation rate was 2.15 g ha-1 day-1, with half-life higher than 182 days.

  18. Persistency of milk yield in Indonesian Holstein cows

    Science.gov (United States)

    Widyas, N.; Putra, F. Y.; Nugroho, T.; Pramono, A.; Susilowati, A.; Sutarno; Prastowo, S.

    2018-03-01

    Milk yield is an important trait in dairy industry; thus, information regarding this phenotype is essential to measure the productivity of a farm. Total milk yield in one lactation period was often predicted using information from samples collected within certain time intervals. The rate of change of milk production between two-time intervals is defined as persistency. This article aims to estimate the persistency of milk yield between lactation 1, 2 and 3 in Indonesian Friesian Holstein (IFH) cows. Data was collected from Limpakuwus stable, Baturraden Dairy Cattle Breeding Centre, Central Java Indonesia. Records were obtained from cows which started lactating on 2013 until the end of third lactation around the beginning of 2016. Milk yield from the first (L1), second (L2) and third (L3) lactations of 21 cows were recorded in kilograms. Samples were collected in 30 days basis interval started from the 10th day of lactation up to the 10th month. In this population, the cows first calving was around February – April 2013; while the second and third calving occurred all over the relevant year. The mean of milk yield for L1, L2 and L3 were 17.77±3.70, 16.09±5.17 and 13.73±4.02 Kg respectively. The peak of milk yields was achieved at the second month of the lactation for L1, L2 and L3. The persistency from the second to the tenth test days were 97, 93 and 94% for L1, L2 and L3, respectively. Milk yield persistency is representing ability of cow in maintain milk production after peak during lactation period. The more persistent shows better performance of dairy cattle as well as farm management. For that, persistency value could be used as valuable information in evaluating the management in Indonesian dairy farms.

  19. Persistent cough in an adolescent.

    Science.gov (United States)

    Stein, M T; Harper, G; Chen, J

    1999-12-01

    Jessica, a 14-year-old girl with a history of asthma, went to her pediatrician's office because of a persistent cough. She had been coughing for at least 3 months with occasional cough-free periods of less than a few days. The cough was nonproductive and was not accompanied by fever, rhinorrhea, or facial or chest pain. Jessica and her mother observed that the cough increased with exercise and typically was not present during sleep. She has used two metered-dose inhalers--albuterol and cromolyn--without any change in the cough pattern. For the past 5 years, Jessica has had mild asthma responsive to albuterol. She enjoys running on the cross-country team, soccer, and dancing. She is an average student and denies any change in academic performance. She has never been hospitalized or had an emergency department visit for asthma or pneumonia. There has been no recent travel or exposure to a person with a chronic productive cough, tobacco smoke, or a live-in pet. Jessica lives with her mother and younger sister in a 10-year-old, carpeted apartment without any evidence of mold or recent renovation. In the process of taking the history, the pediatrician noticed that Jessica coughed intermittently, with two or three coughs during each episode. At times, the cough was harsh; at other times, it was a quiet cough, as if she were clearing her throat. She was cooperative, without overt anxiety or respiratory distress. After a complete physical examination with normal findings, the pediatrician interviewed Jessica and her mother alone. Jessica's parents had been divorced for the past 6 years. She lived with her mother but visited her father, and his new family with two young children, every weekend. She spoke about this arrangement comfortably and said that she loved her father and mother but didn't like the tension she experienced at her father's home. "I don't like adults arguing when kids are around." When asked why she thought the cough persisted so long, she commented in a

  20. Predictors of duloxetine adherence and persistence in patients with fibromyalgia

    Directory of Open Access Journals (Sweden)

    Cui Z

    2012-06-01

    Full Text Available Zhanglin Cui, Yang Zhao, Diego Novick, Douglas FariesEli Lilly and Company, Indianapolis, IN, USAObjectives: Adherence to medication for the treatment of fibromyalgia (FM is predictive of lower overall health-care costs, and thus a lower burden on both patients and providers. The objectives of this study were to examine the predictors of adherence to and persistence with duloxetine therapy among commercially insured FM patients, and to identify subgroups of patients with high duloxetine persistence and adherence.Study design: This cross-sectional, retrospective study analyzed medical and pharmacy records over 1 year for patients in the US aged 18–64 years with FM who initiated (no prior 90-day use duloxetine treatment in 2008.Methods: Adherence to duloxetine was measured by medication possession ratio (MPR, with high adherence defined as MPR ≥ 0.8. Persistence was defined as the duration of therapy from the index date to the earliest of: the ending date of the last prescription, the date of the first gap of >15 days between prescriptions, or the end of the study period (12 months. Demographic and clinical predictors of adherence were examined via multiple logistic regression (MLR, and subgroups of duloxetine-persistent and -adherent patients were identified using classification and regression trees (CART.Results: Among 4660 duloxetine patients, 33% achieved high adherence. Factors associated with high adherence from MLR included older age, North Central and Northeast regions, prior venlafaxine, pregabalin, selective serotonin reuptake inhibitor (SSRI, or other antidepressant use, or comorbid dyslipidemia or osteoarthritis (all P < 0.05. CART analysis revealed that patients with prior antidepressant use, aged ≥46, or prior osteoarthritis had higher MPR (all P < 0.05, and patients aged ≥45 with a history of SSRI, venlafaxine, or anticonvulsant use had longer duration of therapy (all P < 0.05.Conclusions: Patients with high adherence to and

  1. Long-term anti-HBs antibody persistence following infant vaccination against hepatitis B and evaluation of anamnestic response: a 20-year follow-up study in Thailand.

    Science.gov (United States)

    Poovorawan, Yong; Chongsrisawat, Voranush; Theamboonlers, Apiradee; Crasta, Priya Diana; Messier, Marc; Hardt, Karin

    2013-08-01

    Hepatitis B vaccine has been available worldwide since the mid-1980s. This vaccine was evaluated in a clinical trial in Thailand, conducted on subjects born to hepatitis B surface antigen positive and hepatitis B e-antigen positive mothers and vaccinated according to a 4-dose schedule at 0, 1, 2 and 12 mo of age and a single dose of hepatitis B immunoglobulin concomitantly at birth. All enrolled subjects seroconverted and were followed for 20 y to assess the persistence of antibody to the hepatitis B surface antigen (anti-HBs) (NCT00240539). At year 20, 64% of subjects had anti-HBs antibody concentrations≥10 milli-international units per milli liter (mIU/ml) and 92% of subjects had detectable levels (≥3.3 mIU/ml) of anti-HBs antibodies. At year 20, subjects with anti-HBs antibody titermemory (NCT00657657). Anamnestic response to the challenge dose was observed in 96.6% of subjects with an 82-fold (13.2 to 1082.4 mIU/ml) increase in anti-HBs antibody geometric mean concentrations. This study confirms the long-term immunogenicity of the 4-dose regimen of the HBV vaccine eliciting long-term persistence of antibodies and immune memory against hepatitis B for up to at least 20 y after vaccination.

  2. Gender and race/ethnic differences in the persistence of alcohol, drug, and poly-substance use disorders.

    Science.gov (United States)

    Evans, Elizabeth A; Grella, Christine E; Washington, Donna L; Upchurch, Dawn M

    2017-05-01

    To examine gender and racial/ethnic differences in the effect of substance use disorder (SUD) type on SUD persistence. Data were provided by 1025 women and 1835 men from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to examine whether gender and race/ethnicity (Non-Hispanic White, Black, Hispanic) moderate the effects of DSM-IV defined past-12 month SUD type (alcohol, drug, poly-substance) on SUD persistence at 3-year follow-up, controlling for covariates. Using gender-stratified weighted binary logistic regression, we examined predictors of SUD persistence, tested an SUD type by race/ethnicity interaction term, and calculated and conducted Bonferroni corrected pairwise comparisons of predicted probabilities. SUD persistence rates at 3-year follow-up differed for SUD type by gender by race/ethnicity sub-group, and ranged from 31% to 81%. SUD persistence rates were consistently higher among poly-substance users; patterns were mixed in relation to gender and race/ethnicity. Among women, alcohol disordered Hispanics were less likely to persist than Whites. Among men, drug disordered Hispanics were less likely to persist than Whites. Also, Black men with an alcohol or drug use disorder were less likely to persist than Whites, but Black men with a poly-substance use disorder were more likely to persist than Hispanics. The effect of SUD type on SUD persistence varies by race/ethnicity, and the nature of these relationships is different by gender. Such knowledge could inform tailoring of SUD screening and treatment programs, potentially increasing their impact. Published by Elsevier B.V.

  3. Links between Family Social Status and Preschoolers' Persistence: The Role of Maternal Values and Quality of Parenting

    Science.gov (United States)

    Mokrova, Irina L.; O'Brien, Marion; Calkins, Susan D.; Leerkes, Esther M.; Marcovitch, Stuart

    2012-01-01

    Children who develop persistence in the preschool years are likely to function more effectively during the transition into school. In this study of 231 3-year-old children and their mothers, we examined the relations among family social status, maternal values of self-direction, quality of parenting, and children's persistence in challenging…

  4. Patients with persistent medically unexplained physical symptoms

    DEFF Research Database (Denmark)

    A, Aamland; Malterud, Kirsti; Werner, E.

    2014-01-01

    for all variables and split analysis on gender and age. RESULTS: The GPs registered 526 patients among their total of 17 688 consultations, giving a consultation prevalence of persistent MUPS of 3%. The mean age of patients was 46 years, and 399 (76%) were women. The most frequent group of symptoms...... was musculoskeletal problems, followed by asthenia/fatigue. There was no significant gender difference in symptom pattern. Almost half of the patients were currently working (45%), significantly more men. The major GP management strategy was supportive counseling. CONCLUSION: A consultation prevalence rate of 3......% implies that patients with persistent MUPS are common in general practice. Our study disclosed heterogeneity among the patients such as differences in employment status, which emphasizes the importance of personalized focus rather than unsubstantiated stereotyping of "MUPS patients" as a group....

  5. Physical trust-based persistent authentication

    DEFF Research Database (Denmark)

    Fujita, Masahiro; Jensen, Christian D.; Arimura, Shiori

    2015-01-01

    propose a new type of persistent authentication, called Persistent Authentication Based On physical Trust (PABOT). PABOT uses a context of “physical trust relationship” that is built by visual contact between users, and thus can offer a persistent authentication mechanism with better usability and higher...

  6. Initiation, desistance, and persistence of men's sexual coercion.

    Science.gov (United States)

    Hall, Gordon C Nagayama; DeGarmo, David S; Eap, Sopagna; Teten, Andra L; Sue, Stanley

    2006-08-01

    Patterns of sexually coercive behavior were examined among 266 Asian American and 299 European American men over 1 year. Noncoercer (n = 358), desister (n = 120), initiator (n = 39), and persistent (n = 48) sexually coercive groups were identified. The strongest predictor of sexual coercion was past sexual coercion. Persistent sexual coercers were higher than the other groups in delinquency and hostile masculinity and were nearly twice as likely to engage in laboratory sexual harassment. Loss of face attenuated self-reported sexual coercion and laboratory sexual harassment risk among Asian Americans and attenuated only laboratory sexual harassment risk among European Americans. These findings suggest that the heterogeneity of sexually coercive behavior and ethnicity are important research and clinical considerations.

  7. Persisting mathematics and science high school teachers: A Q-methodology study

    Science.gov (United States)

    Robbins-Lavicka, Michelle M.

    There is a lack of qualified mathematics and science teachers at all levels of education in Arkansas. Lasting teaching initiative programs are needed to address retention so qualified teachers remain in the classroom. The dearth of studies regarding why mathematics and science teachers persist in the classroom beyond the traditional 5-year attrition period led this Q-methodological study to evaluate the subjective perceptions of persistent mathematics and science teachers to determine what makes them stay. This study sought to understand what factors persisting mathematics and science teachers used to explain their persistence in the classroom beyond 5 years and what educational factors contributed to persisting mathematics and science teachers. Q-methodology combines qualitative and quantitative techniques and provided a systematic means to investigate personal beliefs by collecting a concourse, developing a Q-sample and a person-sample, conducting a Q-sorting process, and analyzing the data. The results indicated that to encourage longevity within mathematics and science classrooms (a) teachers should remain cognizant of their ability to influence student attitudes toward teaching; (b) administrators should provide support for teachers and emphasize the role and importance of professional development; and (c) policy makers should focus their efforts and resources on developing recruitment plans, including mentorship programs, while providing and improving financial compensation. Significantly, the findings indicate that providing mentorship and role models at every level of mathematics and science education will likely encourage qualified teachers to remain in the mathematics and science classrooms, thus increasing the chance of positive social change.

  8. A 3-year multi-food study of the presence and persistence of Listeria monocytogenes in 54 small food businesses in Ireland.

    Science.gov (United States)

    Leong, Dara; NicAogáin, Kerrie; Luque-Sastre, Laura; McManamon, Oisin; Hunt, Karen; Alvarez-Ordóñez, Avelino; Scollard, Johann; Schmalenberger, Achim; Fanning, Séamus; O'Byrne, Conor; Jordan, Kieran

    2017-05-16

    The problem of assessing the occurrence of the food-borne pathogen Listeria monocytogenes in the food chain, and therefore the risk of exposure of the human population, is often challenging because of the limited scope of some studies. In this study the occurrence of L. monocytogenes in food from four major food groups, dairy products, meats, seafood and vegetables, and associated food processing environments in Ireland was studied over a three-year period. Fifty-four small food businesses participated in the study and sent both food and environmental samples every 2months between 2013 and 2015. L. monocytogenes was isolated using the ISO11290 standard method. Confirmation of L. monocytogenes and identification of serogroups were achieved using a multiplex PCR assay, and for some isolates serotype was determined using commercial antisera. Pulsed- field gel electrophoresis (PFGE) analysis was performed on all isolates allowing the relatedness of isolates from different food businesses to be compared nationwide. In total, 86 distinct pulsotypes were identified. The overall occurrence of L. monocytogenes in food samples was 4.2%, while in environmental samples it was 3.8%. In general, the occurrence of L. monocytogenes in food businesses decreased over the course of the study, presumably reflecting increased awareness and vigilance. The majority of the pulsotypes detected were unique to a particular food group (63/86), while only three pulsotypes were found in all four food groups investigated. The highest occurrence in food was found in the meat category (7.5%) while seafood had the lowest rate of occurrence (1.8%). Seventeen of the pulsotypes detected in the study were persistent, where persistence was defined as repeated isolation from a single facility with a minimum time interval of 6months. Using PFGE, 11 of the pulsotypes identified in this study were indistinguishable from those of 11 clinical isolates obtained from patients in Ireland over the last 4years

  9. Peripheral Red Blood Cell Split Chimerism as a Consequence of Intramedullary Selective Apoptosis of Recipient Red Blood Cells in a Case of Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Marco Marziali

    2014-08-01

    Full Text Available Allogeneic cellular gene therapy through hematopoietic stem cell transplantation is the only radical cure for congenital hemoglobinopathies like thalassemia and sickle cell anemia. Persistent mixed hematopoietic chimerism (PMC has been described in thalassemia and sickle cell anemia. Here, we describe the clinical course of a 6-year-old girl who had received bone marrow transplant for sickle cell anemia. After the transplant, the patient showed 36% donor hematopoietic stem cells in the bone marrow, whereas in the peripheral blood there was evidence of 80%  circulating donor red blood cells (RBC. The analysis of apoptosis at the Bone Marrow  level suggests that Fas might contribute to the cell death of host erythroid precursors. The increase in NK cells and the regulatory T cell population observed in this patient suggests that these cells might contribute to the condition of mixed chimerism.

  10. Persistence and Variation in Overweight and Obesity Among the Pre-school Population of the Community of Madrid After 2 Years of Follow-up. The ELOIN Cohort.

    Science.gov (United States)

    Ortiz-Marrón, Honorato; Ortiz-Pinto, Maira Alejandra; Cuadrado-Gamarra, José I; Esteban-Vasallo, María; Cortés-Rico, Olga; Rey-Gayo, Loreto; Ordobás, María; Galán, Iñaki

    2018-04-30

    The childhood obesity epidemic is a worldwide public health problem which starts at very early ages. The aim of this study was to determine the persistence of and variation in overweight and obesity among a cohort of children followed up from 4 to 6 years of age. The data were drawn from the ELOIN (Longitudinal Childhood Obesity Study), a population-based cohort in the Community of Madrid, Spain. A total of 2435 children were involved. Weight and height were objectively measured and standardised at 4 (2012-2013) and 6 years of age (2014-2015) by 31 purpose-trained pediatricians. Three reference criteria were used: the World Health Organization (WHO-2006), International Obesity Task Force (IOTF-2000), and Spanish tables of the Orbegozo Foundation 2004, were used to define "absence of excess weight", overweight and obesity. According to the above three classification criteria, between the ages of 4 and 6 years the prevalence of overweight increased from 5.7%-16.5% (range of the 3 criteria) to 8.9%-17.0%, and obesity increased from 3.0%-5.4% to 6.1%-10.1%. Three out of every 4 obese children at age 4 years persisted with obesity at age 6 years, whereas 20.6%-29.3% who were overweight became obese. A total of 8.0% to 16.1% of children maintained "excess weight" (overweight/obesity), 7.9% to 11% were new cases, and 2.2% to 5.9% showed remission. Excess weight increased between the ages of 4 and 6 years. Important variations were observed in weight status susceptible to intervention during well-child visits. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Persistent orofacial muscle pain: Its synonymous terminology and presentation.

    Science.gov (United States)

    Spierings, Egilius L H; Mulder, Maxim J H L

    2017-09-01

    The purpose of the present paper is to describe the presentation of persistent orofacial muscle pain, also commonly referred to as myofascial temporomandibular disorder. In this practice survey, the authors reviewed the demographic and clinical features of 34 patients who were evaluated and diagnosed personally. The majority of the 34 patients were women (82.4%), and their age at consultation averaged 44.6 ± 12.6 (SD) years. The median pain duration was 4.0 years (range: 0.2-34 years). In 97.1% of patients, the pain occurred daily and continuously, and in 51.9% it was unilateral. Chewing or eating made the pain worse in 50% of the patients, and talking in 29.4%. On examination, tightness of the masseter muscle(s) was present in 58.8%, and tenderness in 58.8%. Persistent orofacial muscle pain mostly affects women, generally occurs daily and continuously, and is equally often unilateral and bilateral. Chewing, eating, and talking are the most common aggravating factors, and tightness or tenderness of the masseter muscle(s) is often found on examination.

  12. Viral persistence, latent reservoir, and blips: a review on HIV-1 dynamics and modeling during HAART and related treatment implications

    Energy Technology Data Exchange (ETDEWEB)

    Rong, Libin [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    HIV-1 eradication from infected individuals has not been achieved with the use of highly active antiretroviral therapy (HAART) for a prolonged period of time. The cellular reservoir for HIV-1 in resting memory CD4{sup +} T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time as is able to release replication competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling can help improve our understanding of HIV-1 dynamics in patients on HAART and the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.

  13. Effect of water content on the persistence of 14C-DDT in a soil under cerrado

    International Nuclear Information System (INIS)

    Andrea, M.M. de; Ruegg, E.F.

    1985-01-01

    The influence of moisture on persistence and degradation of 14 C-DDT in a soil under 'cerrado' is studied under laboratory conditions. The persistence of DDT in the Dark Red Latosol medium texture after one year, in spite of a tendency to be more persistente at 1/3 field capacity and less persistent at higher levels of moisture, is related. (Author) [pt

  14. Ten-year survival of patients with oesophageal squamous cell ...

    African Journals Online (AJOL)

    Objectives. The standard predictive factors of actuarial survival such as T and N stage become less important as patients live for more than 10 years after treatment of cancer. Reports of actual 10-year survivors of oesophageal squamous cell carcinoma (SCC) are rare, and demographic and clinicopathological factors ...

  15. Persistence of Two Campylobacter jejuni Strains in Soil and on Spinach Plants

    International Nuclear Information System (INIS)

    Jaderlund, L.; Arthurson, V.; Sessitsch, A.

    2011-01-01

    There are indications that the more frequent use of untreated organic residues for fertilization results in increased risk of contamination with human pathogens. Here, we evaluate the ability of two different strains of Campylobacter jejuni to persist in manure and soil as well as spread to spinach plants. It was revealed that different strategies for inoculation of C. jejuni contribute to the persistence of the bacterium in soil, roots, and shoots. Upon inoculation of the bacteria into manure prior to soil application, the amount of C. jejuni subsequently recovered in soil was higher than that from treatments involving the addition of C. jejuni cells to the soil after plant emergence. Irrespective of the bacterial inoculation dose and strategy employed, the C. jejuni content in soil remained relatively constant, whereas the majority of C. jejuni cells applied to spinach leaves could be recovered during the whole evaluation period of 21 days.

  16. A Multifunctional Biomaterial with NIR Long Persistent Phosphorescence, Photothermal Response and Magnetism.

    Science.gov (United States)

    Wu, Yiling; Li, Yang; Qin, Xixi; Qiu, Jianrong

    2016-09-20

    There are many reports on long persistent phosphors (LPPs) applied in bioimaging. However, there are few reports on LPPs applied in photothermal therapy (PTT), and an integrated system with multiple functions of diagnosis and therapy. In this work, we fabricate effective multifunctional phosphors Zn3 Ga2 SnO8 : Cr(3+) , Nd(3+) , Gd(3+) with NIR persistent phosphorescence, photothermal response and magnetism. Such featured materials can act as NIR optical biolabels and magnetic resonance imaging (MRI) contrast agents for tracking the early cancer cells, but also as photothermal therapeutic agent for killing the cancer cells. This new multifunctional biomaterial is expected to open a new possibility of setting up an advanced imaging-guided therapy system featuring a high resolution for bioimaging and low side effects for the photothermal ablation of tumors. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Persistence of the embryonic lateral marginal vein: report of two cases

    Directory of Open Access Journals (Sweden)

    Rojas Martinez Raúl

    2001-01-01

    Full Text Available PURPOSE: Congenital venous malformations of the lower limbs represent a particular challenge for the vascular surgeon. Persistence of fetal veins is a rare malformation, and the most common is the persistence of the lateral marginal vein usually observed in patients with Klippel-Trenaunnay Syndrome. The persistence of this embryonic vein as an isolated venous malformation without the other characteristics of the Klippel-Trenaunnay Syndrome has not yet been reported. This paper describes two cases. METHODS: Two patients, a 17-year-old male patient and a 16-year-old female, have had since their birth a large venous trunk in the lateral aspect of the right leg and thigh. The limbs underwent duplex scanning and phlebography. The surgical removal of the lateral marginal vein was performed. RESULTS: Surgical treatment resulted in very good functional and aesthetic results. Follow-up at 26 months showed no evidence of varicose vein recurrence. CONCLUSIONS: To achieve good results, surgical intervention may be indicated in cases of orthopedic deformity, hemorrhage, symptomatic, and unaesthetic lesions.

  18. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Science.gov (United States)

    Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

    2017-01-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  19. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Directory of Open Access Journals (Sweden)

    Meghna Verma

    Full Text Available Human immunodeficiency virus (HIV-infected patients are at an increased risk of co-infection with human papilloma virus (HPV, and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1 cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  20. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

    Science.gov (United States)

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

  1. Migration and Persistence of Human Influenza A Viruses, Vietnam, 2001–2008

    Science.gov (United States)

    Le, Mai Quynh; Lam, Ha Minh; Cuong, Vuong Duc; Lam, Tommy Tsan-Yuk; Halpin, Rebecca A; Wentworth, David E; Hien, Nguyen Tran; Thanh, Le Thi; Phuong, Hoang Vu Mai; Horby, Peter

    2013-01-01

    Understanding global influenza migration and persistence is crucial for vaccine strain selection. Using 240 new human influenza A virus whole genomes collected in Vietnam during 2001–2008, we looked for persistence patterns and migratory connections between Vietnam and other countries. We found that viruses in Vietnam migrate to and from China, Hong Kong, Taiwan, Cambodia, Japan, South Korea, and the United States. We attempted to reduce geographic bias by generating phylogenies subsampled at the year and country levels. However, migration events in these phylogenies were still driven by the presence or absence of sequence data, indicating that an epidemiologic study design that controls for prevalence is required for robust migration analysis. With whole-genome data, most migration events are not detectable from the phylogeny of the hemagglutinin segment alone, although general migratory relationships between Vietnam and other countries are visible in the hemagglutinin phylogeny. It is possible that virus lineages in Vietnam persisted for >1 year. PMID:24188643

  2. Stochastic models of cell motility

    DEFF Research Database (Denmark)

    Gradinaru, Cristian

    2012-01-01

    Cell motility and migration are central to the development and maintenance of multicellular organisms, and errors during this process can lead to major diseases. Consequently, the mechanisms and phenomenology of cell motility are currently under intense study. In recent years, a new...... interdisciplinary field focusing on the study of biological processes at the nanoscale level, with a range of technological applications in medicine and biological research, has emerged. The work presented in this thesis is at the interface of cell biology, image processing, and stochastic modeling. The stochastic...... models introduced here are based on persistent random motion, which I apply to real-life studies of cell motility on flat and nanostructured surfaces. These models aim to predict the time-dependent position of cell centroids in a stochastic manner, and conversely determine directly from experimental...

  3. Basal Cell Carcinoma: 10 Years of Experience

    International Nuclear Information System (INIS)

    Cigna, E.; Tarallo, M.; Maruccia, M.; Sorvillo, V.; Pollastrini, A.; Scuderi, N.

    2011-01-01

    Introduction. Basal cell carcinoma (BCC) is a locally invasive malignant epidermal tumour. Incidence is increasing by 10% per year; incidence of metastases is minimal, but relapses are frequent (40%-50%). The complete excision of the BCC allows reduction of relapse. Materials and Methods. The study cohort consists of 1123 patients underwent surgery for basal cell carcinoma between 1999 and 2009. Patient and tumor characteristics recorded are: age; gender; localization (head and neck, trunk, and upper and lower extremities), tumor size, excisional margins adopted, and relapses. Results. The study considered a group of 1123 patients affected by basal cell carcinoma. Relapses occurred in 30 cases (2,67%), 27 out of 30 relapses occurred in noble areas, where peripheral margin was <3mm. Incompletely excised basal cell carcinoma occurred in 21 patients (1,87%) and were treated with an additional excision. Discussion. Although guidelines indicate 3mm p