Support for viral persistence in bats from age-specific serology and models of maternal immunity.

Science.gov (United States)

Peel, Alison J; Baker, Kate S; Hayman, David T S; Broder, Christopher C; Cunningham, Andrew A; Fooks, Anthony R; Garnier, Romain; Wood, James L N; Restif, Olivier

2018-03-01

Spatiotemporally-localised prediction of virus emergence from wildlife requires focused studies on the ecology and immunology of reservoir hosts in their native habitat. Reliable predictions from mathematical models remain difficult in most systems due to a dearth of appropriate empirical data. Our goal was to study the circulation and immune dynamics of zoonotic viruses in bat populations and investigate the effects of maternally-derived and acquired immunity on viral persistence. Using rare age-specific serological data from wild-caught Eidolon helvum fruit bats as a case study, we estimated viral transmission parameters for a stochastic infection model. We estimated mean durations of around 6 months for maternally-derived immunity to Lagos bat virus and African henipavirus, whereas acquired immunity was long-lasting (Lagos bat virus: mean 12 years, henipavirus: mean 4 years). In the presence of a seasonal birth pulse, the effect of maternally-derived immunity on virus persistence within modelled bat populations was highly dependent on transmission characteristics. To explain previous reports of viral persistence within small natural and captive E. helvum populations, we hypothesise that some bats must experience prolonged infectious periods or within-host latency. By further elucidating plausible mechanisms of virus persistence in bat populations, we contribute to guidance of future field studies.

Persistence of attenuated HIV-1 rev alleles in an epidemiologically linked cohort of long-term survivors infected with nef-deleted virus

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Wesselingh Steven L

2007-07-01

Full Text Available Abstract Background The Sydney blood bank cohort (SBBC of long-term survivors consists of multiple individuals infected with nef-deleted, attenuated strains of human immunodeficiency virus type 1 (HIV-1. Although the cohort members have experienced differing clinical courses and now comprise slow progressors (SP as well as long-term nonprogressors (LTNP, longitudinal analysis of nef/long-terminal repeat (LTR sequences demonstrated convergent nef/LTR sequence evolution in SBBC SP and LTNP. Thus, the in vivo pathogenicity of attenuated HIV-1 strains harboured by SBBC members is dictated by factors other than nef/LTR. Therefore, to determine whether defects in other viral genes contribute to attenuation of these HIV-1 strains, we characterized dominant HIV-1 rev alleles that persisted in 4 SBBC subjects; C18, C64, C98 and D36. Results The ability of Rev derived from D36 and C64 to bind the Rev responsive element (RRE in RNA binding assays was reduced by approximately 90% compared to Rev derived from HIV-1NL4-3, C18 or C98. D36 Rev also had a 50–60% reduction in ability to express Rev-dependent reporter constructs in mammalian cells. In contrast, C64 Rev had only marginally decreased Rev function despite attenuated RRE binding. In D36 and C64, attenuated RRE binding was associated with rare amino acid changes at 3 highly conserved residues; Gln to Pro at position 74 immediately N-terminal to the Rev activation domain, and Val to Leu and Ser to Pro at positions 104 and 106 at the Rev C-terminus, respectively. In D36, reduced Rev function was mapped to an unusual 13 amino acid extension at the Rev C-terminus. Conclusion These findings provide new genetic and mechanistic insights important for Rev function, and suggest that Rev function, not Rev/RRE binding may be rate limiting for HIV-1 replication. In addition, attenuated rev alleles may contribute to viral attenuation and long-term survival of HIV-1 infection in a subset of SBBC members.

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

Directory of Open Access Journals (Sweden)

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.

The impact of inter-annual variability of annual cycle on long-term persistence of surface air temperature in long historical records

Science.gov (United States)

Deng, Qimin; Nian, Da; Fu, Zuntao

2018-02-01

Previous studies in the literature show that the annual cycle of surface air temperature (SAT) is changing in both amplitude and phase, and the SAT departures from the annual cycle are long-term correlated. However, the classical definition of temperature anomalies is based on the assumption that the annual cycle is constant, which contradicts the fact of changing annual cycle. How to quantify the impact of the changing annual cycle on the long-term correlation of temperature anomaly variability still remains open. In this paper, a recently developed data adaptive analysis tool, the nonlinear mode decomposition (NMD), is used to extract and remove time-varying annual cycle to reach the new defined temperature anomalies in which time-dependent amplitude of annual cycle has been considered. By means of detrended fluctuation analysis, the impact induced by inter-annual variability from the time-dependent amplitude of annual cycle has been quantified on the estimation of long-term correlation of long historical temperature anomalies in Europe. The results show that the classical climatology annual cycle is supposed to lack inter-annual fluctuation which will lead to a maximum artificial deviation centering around 600 days. This maximum artificial deviation is crucial to defining the scaling range and estimating the long-term persistence exponent accurately. Selecting different scaling range could lead to an overestimation or underestimation of the long-term persistence exponent. By using NMD method to extract the inter-annual fluctuations of annual cycle, this artificial crossover can be weakened to extend a wider scaling range with fewer uncertainties.

Term Structure Persistence

OpenAIRE

Abbritti, M. (Mirko); Gil-Alana, L.A. (Luis A.); Lovcha, Y. (Yuliya); Moreno, A. (Antonio)

2012-01-01

Stationary I(0) models employed in yield curve analysis typically imply an unrealistically low degree of volatility in long-run short-rate expectations due to fast mean reversion. In this paper we propose a novel multivariate affine term structure model with a two-fold source of persistence in the yield curve: Long-memory and short-memory. Our model, based on an I(d) specification, nests the I(0) and I(1) models as special cases and the I(0) model is decisively rejected by the data. Our model...

Long-Term Persistence of Pseudogymnoascus destructans, the Causative Agent of White-Nose Syndrome, in the Absence of Bats.

Science.gov (United States)

Hoyt, Joseph R; Langwig, Kate E; Okoniewski, Joseph; Frick, Winifred F; Stone, Ward B; Kilpatrick, A Marm

2015-06-01

Wildlife diseases have been implicated in the declines and extinctions of several species. The ability of a pathogen to persist outside its host, existing as an "environmental reservoir", can exacerbate the impact of a disease and increase the likelihood of host extinction. Pseudogymnoascus destructans, the fungal pathogen that causes white-nose syndrome in bats, has been found in cave soil during the summer when hibernating bats had likely been absent for several months. However, whether the pathogen can persist over multiple years in the absence of bats is unknown, and long-term persistence of the pathogen can influence whether hibernacula where bats have been locally extirpated due to disease can be subsequently recolonized. Here, we show that P. destructans is capable of long-term persistence in the laboratory in the absence of bats. We cultured P. destructans from dried agar plates that had been kept at 5°C and low humidity conditions (30-40% RH) for more than 5 years. This suggests that P. destructans can persist in the absence of bats for long periods which may prevent the recolonization of hibernation, sites where bat populations were extirpated. This increases the extinction risk of bats affected by this disease.

An assessment of the long-term persistence of prion infectivity in aquatic environments

International Nuclear Information System (INIS)

Marín-Moreno, Alba; Espinosa, Juan-Carlos; Fernández-Borges, Natalia; Píquer, Juan; Girones, Rosina; Andreoletti, Olivier; Torres, Juan-María

2016-01-01

The environment plays a key role in horizontal transmission of prion diseases, since prions are extremely resistant to classical inactivation procedures. In prior work, we observed the high stability of bovine spongiform encephalopathy (BSE) infectivity when these prions were incubated in aqueous media such as phosphate-buffered saline (PBS) or wastewater for nearly nine months. As a continuation of this experiment, the same samples were maintained in PBS or wastewater for five additional years and residual BSE infectivity was assessed in bovine PrP C transgenic mice. Over this long time period (more than six years), BSE infectivity was reduced by three and one orders of magnitude in wastewater and PBS respectively. To rule out a possible agent specific effect, sheep scrapie prions were subjected to the same experimental protocol, using eight years as the experimental end-point. No significant reduction in scrapie infectivity was observed over the first nine months of wastewater incubation while PBS incubation for eight years only produced a two logarithmic unit reduction in infectivity. By contrast, the dynamics of PrP Res persistence was different, disappearing progressively over the first year. The long persistence of prion infectivity observed in this study for two different agents provides supporting evidence of the assumed high stability of these agents in aquatic environments and that environmental processes or conventional wastewater treatments with low retention times would have little impact on prion infectivity. These results could have great repercussions in terms of risk assessment and safety for animals and human populations. - Highlights: • Prion infectivity resists long term incubations in aquatic environments. • Infectivity persistence in wastewater is reduced when compared to PBS. • In this study PrPRes fails as a marker for prion detection. • Mice bioassay is the most powerful tool for assessing prion presence. • Wastewater conventional

An assessment of the long-term persistence of prion infectivity in aquatic environments

Energy Technology Data Exchange (ETDEWEB)

Marín-Moreno, Alba; Espinosa, Juan-Carlos; Fernández-Borges, Natalia; Píquer, Juan [Centro de Investigación en Sanidad Animal, CISA-INIA, Carretera Algete-El Casar S/n, Valdeolmos, 28130 Madrid (Spain); Girones, Rosina [Department of Microbiology, University of Barcelona, Diagonal 643, 08028 Barcelona (Spain); Andreoletti, Olivier [UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse (France); Torres, Juan-María, E-mail: jmtorres@inia.es [Centro de Investigación en Sanidad Animal, CISA-INIA, Carretera Algete-El Casar S/n, Valdeolmos, 28130 Madrid (Spain)

2016-11-15

The environment plays a key role in horizontal transmission of prion diseases, since prions are extremely resistant to classical inactivation procedures. In prior work, we observed the high stability of bovine spongiform encephalopathy (BSE) infectivity when these prions were incubated in aqueous media such as phosphate-buffered saline (PBS) or wastewater for nearly nine months. As a continuation of this experiment, the same samples were maintained in PBS or wastewater for five additional years and residual BSE infectivity was assessed in bovine PrP{sup C} transgenic mice. Over this long time period (more than six years), BSE infectivity was reduced by three and one orders of magnitude in wastewater and PBS respectively. To rule out a possible agent specific effect, sheep scrapie prions were subjected to the same experimental protocol, using eight years as the experimental end-point. No significant reduction in scrapie infectivity was observed over the first nine months of wastewater incubation while PBS incubation for eight years only produced a two logarithmic unit reduction in infectivity. By contrast, the dynamics of PrP{sup Res} persistence was different, disappearing progressively over the first year. The long persistence of prion infectivity observed in this study for two different agents provides supporting evidence of the assumed high stability of these agents in aquatic environments and that environmental processes or conventional wastewater treatments with low retention times would have little impact on prion infectivity. These results could have great repercussions in terms of risk assessment and safety for animals and human populations. - Highlights: • Prion infectivity resists long term incubations in aquatic environments. • Infectivity persistence in wastewater is reduced when compared to PBS. • In this study PrPRes fails as a marker for prion detection. • Mice bioassay is the most powerful tool for assessing prion presence. • Wastewater

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

Science.gov (United States)

Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-05-17

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

Persistent inhibition of hippocampal long-term potentiation in vivo by learned helplessness stress.

Science.gov (United States)

Ryan, Benedict K; Vollmayr, Barbara; Klyubin, Igor; Gass, Peter; Rowan, Michael J

2010-06-01

The persistent cognitive disruptive effects of stress have been strongly implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (learned helplessness, inhibited LTP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LTP inhibition. Moreover, LTP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress.

Long term in vivo imaging with Cr{sup 3+} doped spinel nanoparticles exhibiting persistent luminescence

Energy Technology Data Exchange (ETDEWEB)

Viana, B., E-mail: bruno.viana@chimie-paristech.fr [PSL Research University, Chimie ParisTech−CNRS, Institut de Recherche de Chimie Paris, 75005 Paris (France); Chimie-ParisTech, Paris cedex F-75231 (France); Sharma, S.K.; Gourier, D. [PSL Research University, Chimie ParisTech−CNRS, Institut de Recherche de Chimie Paris, 75005 Paris (France); Chimie-ParisTech, Paris cedex F-75231 (France); Maldiney, T.; Teston, E.; Scherman, D. [Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), CNRS UMR 8258, INSERM U 1022, Paris cedex F-75270 (France); Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris cedex F-75270 (France); Chimie-ParisTech, Paris cedex F-75231 (France); Richard, C., E-mail: cyrille.richard@parisdescartes.fr [Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), CNRS UMR 8258, INSERM U 1022, Paris cedex F-75270 (France); Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris cedex F-75270 (France); Chimie-ParisTech, Paris cedex F-75231 (France)

2016-02-15

Persistent luminescence is a singular property of some materials which are able to store the excitation or light irradiation energy at intrinsic traps or defects before slowly emitting lower energy photons within several hours. When such compounds are prepared as nanoparticles (NPs), when functionalization is realized to get colloidal materials well dispersed in aqueous medium, such nanoprobes open the use of the persistent luminescence for bioimaging applications. Recently, the numbers of in vivo applications increased with new modalities and new expectations. In this review, we focused our attention on the ZnGa{sub 2}O{sub 4}:Cr (ZGO:Cr) nanoparticles. When ZnGa{sub 2}O{sub 4} (ZGO), a normal spinel is doped with Cr{sup 3+} ions, a high brightness persistent luminescence material with an emission spectrum perfectly matching the transparency window of living tissues is obtained. It allows in vivo mouse imaging with an excellent target-to-background ratio. One interesting characteristic of ZGO:Cr lies in the fact that its persistent luminescence can be excited with orange/red light, well below its band gap energy and in the transparency window of living tissues. This important property allows multiple re-excitations to perform long term bioimaging. Antisite defects of the direct spinel structure are assumed to provide shallow traps which store the excitation light. Charge release by room temperature thermal excitation and recombination center, here trivalent chromium, are responsible for the persistent luminescence. Following a primary excitation (UV or visible), one also observed that trapped charges can be released under 977 nm light stimulation for several spinel gallate materials, therefore increasing the modalities and the materials envisioned for in vivo excitation of these NPs. - Highlights: • Review of the persistent luminescence for bio-imaging. • Long term bioimaging by in vivo excitation and photostimulation. • Challenges and main advances in the

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.

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

Science.gov (United States)

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

2017-11-14

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

LONG-TERM OUTCOME OF THE DIFFERENT TREATMENT ALTERNATIVES FOR RECURRENT AND PERSISTENT CUSHING DISEASE.

Science.gov (United States)

Espinosa-de-Los-Monteros, Ana Laura; Sosa-Eroza, Ernesto; Espinosa, Etual; Mendoza, Victoria; Arreola, Rocio; Mercado, Moises

2017-07-01

Treatment alternatives for persistent and recurrent Cushing disease (CD) include pituitary surgical re-intervention, radiation therapy (RT), pharmacotherapy, and bilateral adrenalectomy (BA). The decision of which of these alternatives is better suited for the individual patient rests on clinical judgment and the availability of resources. This retrospective cohort study was performed at a referral center to evaluate the long-term efficacy of different secondary interventions for persistent and recurrent CD. We evaluated the hospital charts of 84 patients (77 female, median age 34 years, median follow up 6.3 years) with CD diagnosed, treated, and followed at our multidisciplinary clinic according to a pre-established protocol. Of the 81 patients who were initially treated with transsphenoidal surgery (TSS), 61.7% had a long-lasting remission, 16% had persistent disease, and 22% achieved remission but relapsed during follow-up. The most frequently used secondary treatment was pituitary re-intervention, followed by ketoconazole, RT, and BA. Early remissions were observed in 66.6% of the re-operated and in 58.3% of the radiated patients; long-lasting remission was achieved in 33.3% and 41.6% of these patients, respectively. Nelson syndrome developed in 41.6% of the patients who underwent BA. Upon last follow-up, 88% of all the patients are in remission, and 9.5% are biochemically controlled with ketoconazole. The efficacy of treatment alternatives for recurrent or persistent CD varies considerably among patients and multiple interventions are often required to achieve long-lasting remission. ACTH = adrenocorticotrophic hormone; BA = bilateral adrenalectomy; CBG = cabergoline; CD = Cushing disease; CV = coefficient of variation; DXM = dexamethasone; IQR = interquartile range; RT = radiation therapy; SRS = stereotactic radiosurgery; TSS = transsphenoidal surgery; UFC = urinary free cortisol; ULN = upper limit of normal.

Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis

Science.gov (United States)

Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

2014-01-01

Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. PMID:24965611

No Evidence of Viral Transmission following Long-Term Implantation of Agarose Encapsulated Porcine Islets in Diabetic Dogs

Directory of Open Access Journals (Sweden)

Lawrence S. Gazda

2014-01-01

Full Text Available We have previously described the use of a double coated agarose-agarose porcine islet macrobead for the treatment of type I diabetes mellitus. In the current study, the long-term viral safety of macrobead implantation into pancreatectomized diabetic dogs treated with pravastatin (n=3 was assessed while 2 dogs served as nonimplanted controls. A more gradual return to preimplant insulin requirements occurred after a 2nd implant procedure (days 148, 189, and >652 when compared to a first macrobead implantation (days 9, 21, and 21 in all macrobead implanted animals. In all three implanted dogs, porcine C-peptide was detected in the blood for at least 10 days following the first implant and for at least 26 days following the second implant. C-peptide was also present in the peritoneal fluid of all three implanted dogs at 6 months after 2nd implant and in 2 of 3 dogs at necropsy. Prescreening results of islet macrobeads and culture media prior to transplantation were negative for 13 viruses. No evidence of PERV or other viral transmission was found throughout the study. This study demonstrates that the long-term (2.4 years implantation of agarose-agarose encapsulated porcine islets is a safe procedure in a large animal model of type I diabetes mellitus.

Future climate change is predicted to shift long-term persistence zones in the cold-temperate kelp Laminaria hyperborea.

Science.gov (United States)

Assis, Jorge; Lucas, Ana Vaz; Bárbara, Ignacio; Serrão, Ester Álvares

2016-02-01

Global climate change is shifting species distributions worldwide. At rear edges (warmer, low latitude range margins), the consequences of small variations in environmental conditions can be magnified, producing large negative effects on species ranges. A major outcome of shifts in distributions that only recently received attention is the potential to reduce the levels of intra-specific diversity and consequently the global evolutionary and adaptive capacity of species to face novel disturbances. This is particularly important for low dispersal marine species, such as kelps, that generally retain high and unique genetic diversity at rear ranges resulting from long-term persistence, while ranges shifts during climatic glacial/interglacial cycles. Using ecological niche modelling, we (1) infer the major environmental forces shaping the distribution of a cold-temperate kelp, Laminaria hyperborea (Gunnerus) Foslie, and we (2) predict the effect of past climate changes in shaping regions of long-term persistence (i.e., climatic refugia), where this species might hypothetically harbour higher genetic diversity given the absence of bottlenecks and local extinctions over the long term. We further (3) assessed the consequences of future climate for the fate of L. hyperborea using different scenarios of greenhouse gas emissions (RCP 2.6 and RCP 8.5). Results show NW Iberia, SW Ireland and W English Channel, Faroe Islands and S Iceland, as regions where L. hyperborea may have persisted during past climate extremes until present day. All predictions for the future showed expansions to northern territories coupled with the significant loss of suitable habitats at low latitude range margins, where long-term persistence was inferred (e.g., NW Iberia). This pattern was particularly evident in the most agressive scenario of climate change (RCP 8.5), likely driving major biodiversity loss, changes in ecosystem functioning and the impoverishment of the global gene pool of L

Viral persistence, liver disease and host response in Hepatitis C-like virus rat model

DEFF Research Database (Denmark)

Trivedi, Sheetal; Murthy, Satyapramod; Sharma, Himanshu

2018-01-01

The lack of a relevant, tractable, and immunocompetent animal model for hepatitis C virus (HCV) has severely impeded investigations of viral persistence, immunity and pathogenesis. In the absence of immunocompetent models with robust HCV infection, homolog hepaciviruses in their natural host could...... potentially provide useful surrogate models. We isolated a rodent hepacivirus (RHV) from wild rats (Rattus norvegicus), RHV-rn1, acquired the complete viral genome sequence and developed an infectious reverse genetics system. RHV-rn1 resembles HCV in genomic features including the pattern of polyprotein...... cleavage sites and secondary structures in the viral 5' and 3' UTRs. We used site-directed and random mutagenesis to determine that only the first of the two miR-122 seed sites in viral 5'UTR is required for viral replication and persistence in rats. Next, we used the clone derived virus progeny to infect...

Persistent negative illness perceptions despite long-term biochemical control of acromegaly: novel application of the drawing test

NARCIS (Netherlands)

Tiemensma, Jitske; Pereira, Alberto M.; Romijn, Johannes A.; Broadbent, Elizabeth; Biermasz, Nienke R.; Kaptein, Adrian A.

2015-01-01

Context and objective: Patients with acromegaly have persistent complaints despite long-term biochemical control. Drawings can be used to assess patients' perceptions about their disease. We aimed to explore the utility of the drawing test and its relation to illness perceptions and quality of life

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.

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

Directory of Open Access Journals (Sweden)

Dajana Reuter

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

A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model.

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Iart Luca Shytaj

Full Text Available Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART in a wide range of viremic conditions (10³-10⁷ viral RNA copies/mL in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir, an integrase inhibitor (raltegravir, a protease inhibitor (ritonavir-boosted darunavir and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*10⁵ cells in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR⁺ effector memory CD4⁺ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing

Stress within a Restricted Time Window Selectively Affects the Persistence of Long-Term Memory

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Fang, Qin; Chai, Ning; Zhao, Li-Yan; Xue, Yan-Xue; Luo, Yi-Xiao; Jian, Min; Han, Ying; Shi, Hai-Shui; Lu, Lin; Wu, Ping; Wang, Ji-Shi

2013-01-01

The effects of stress on emotional memory are distinct and depend on the stages of memory. Memory undergoes consolidation and reconsolidation after acquisition and retrieval, respectively. Stress facilitates the consolidation but disrupts the reconsolidation of emotional memory. Previous research on the effects of stress on memory have focused on long-term memory (LTM) formation (tested 24 h later), but the effects of stress on the persistence of LTM (tested at least 1 week later) are unclear. Recent findings indicated that the persistence of LTM requires late-phase protein synthesis in the dorsal hippocampus. The present study investigated the effect of stress (i.e., cold water stress) during the late phase after the acquisition and retrieval of contextual fear memory in rats. We found that stress and corticosterone administration during the late phase (12 h) after acquisition, referred to as late consolidation, selectively enhanced the persistence of LTM, whereas stress during the late phase (12 h) after retrieval, referred to as late reconsolidation, selectively disrupted the restabilized persistence of LTM. Moreover, the effects of stress on the persistence of LTM were blocked by the corticosterone synthesis inhibitor metyrapone, which was administered before stress, suggesting that the glucocorticoid system is involved in the effects of stress on the persistence of LTM. We conclude that stress within a restricted time window after acquisition or retrieval selectively affects the persistence of LTM and depends on the glucocorticoid system. PMID:23544051

Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

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Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

2016-10-01

Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

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

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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.

Regulatory components for treating persistent pain in long-term care.

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Planton, Jonathan; Edlund, Barbara J

2010-04-01

Persistent or chronic pain is frequently reported by older adults and has the potential to dramatically influence quality of life. Estimates indicate that 25% to 50% of community-dwelling older adults experience this kind of pain. This rate is even higher in long-term care facilities, where 50% to 75% of residents have chronic pain syndromes that are untreated or undertreated. To promote optimal pain management and enumerate the responsibilities of skilled nursing facilities to effectively treat and prevent pain, the Centers for Medicare & Medicaid Services released a new pain management surveyor guidance, F-Tag 309, which endorses the presence of an interdisciplinary team approach to pain management that involves the resident. The guidance delineates pain management principles, the need for ongoing professional education in all components of pain management, and emphasizes the important role of appropriate pharmacological treatment in conjunction with nonpharmacological interventions to aggressively manage pain. This directive will help skilled nursing facilities achieve optimal pain management for their residents. Copyright 2010, SLACK Incorporated.

Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis

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Lai, Tianwen; Wang, Shaobin; Xu, Zhiwei; Zhang, Chao; Zhao, Yun; Hu, Yue; Cao, Chao; Ying, Songmin; Chen, Zhihua; Li, Wen; Wu, Bin; Shen, Huahao

2015-01-01

Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i) systematically review the evidence regarding the long-term efficacy of omalizumab in patients with persistent uncontrolled allergic asthma, and to (ii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A comprehensive search for randomized controlled trials (RCTs; ?52 weeks) was perfor...

Evaluation of the Universal Viral Transport system for long-term storage of virus specimens for microbial forensics.

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Hosokawa-Muto, Junji; Fujinami, Yoshihito; Mizuno, Natsuko

2015-08-01

Forensic microbial specimens, including bacteria and viruses, are collected at biocrime and bioterrorism scenes. Although it is preferable that the pathogens in these samples are alive and kept in a steady state, the samples may be stored for prolonged periods before analysis. Therefore, it is important to understand the effects of storage conditions on the pathogens contained within such samples. To evaluate the capacity to preserve viable virus and the viral genome, influenza virus was added to the transport medium of the Universal Viral Transport system and stored for over 3 months at various temperatures, after which virus titrations and quantitative analysis of the influenza hemagglutinin gene were performed. Although viable viruses became undetectable 29 days after the medium was stored at room temperature, viruses in the medium stored at 4°C were viable even after 99 days. A quantitative PCR analysis indicated that the hemagglutinin gene was maintained for 99 days at both 4°C and room temperature. Therefore, long-term storage at 4°C has little effect on viable virus and viral genes, so the Universal Viral Transport system can be useful for microbial forensics. This study provides important information for the handling of forensic virus specimens. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Characterization of EIAV LTR variability and compartmentalization in various reservoir tissues of long-term inapparent carrier ponies

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Reis, Jenner K.P.; Craigo, Jodi K.; Cook, Sheila J.; Issel, Charles J.; Montelaro, Ronald C.

2003-01-01

Dynamic genomic variation resulting in changes in envelope antigenicity has been established as a fundamental mechanism of persistence by equine infectious anemia virus (EIAV), as observed with other lentiviruses, including HIV-1. In addition to the reported changes in envelope sequences, however, certain studies indicate the viral LTR as a second variable EIAV gene, with the enhancer region being designated as hypervariable. These observations have lead to the suggestion that LTR variation may alter viral replication properties to optimize to the microenvironment of particular tissue reservoirs. To test this hypothesis directly, we examined the population of LTR quasispecies contained in various tissues of two inapparent carrier ponies experimentally infected with a reference EIAV biological clone for 18 months. The results of these studies demonstrated that the EIAV LTR is in fact highly conserved with respect to the infecting LTR species after 1.5 years of persistent infection and regardless of the tissue reservoir. Thus, these comprehensive analyses demonstrate for the first time that the EIAV LTR is highly conserved during long-term persistent infection and that the observed variations in viral LTR are associated more with in vitro adaptation to replication in cultured cells rather than in vivo replication in natural target cells

Long-term follow-up of patients with spontaneous clearance of hepatitis C: does viral clearance mean cure?

LENUS (Irish Health Repository)

Iqbal, M

2017-06-01

Up to 40% of patients with hepatitis C virus (HCV) antibodies are negative for HCV RNA at initial evaluation. If there is a risk of viral re-activation, long term follow-up is required with attendant financial, psychological and medical implications. We investigated the risk of re-activation in the Irish anti-D cohort. Information was obtained from the national hepatitis C database which includes data on patients infected by anti-D immunoglobulin in two large outbreaks, 1977-9 and 1991-94. As part of a screening programme, starting in 1994, 64,907 females exposed to anti-D immunoglobulin were evaluated. Three hundred and forty-seven were found to be antibody positive but HCV RNA negative at initial assessment. 93% had subsequent RNA tests. There was no evidence of HCV recurrence in patients whose infection resolved spontaneously. It appears that two initial sequential negative results for HCV RNA are sufficient to confirm spontaneous viral clearance and probable cure of hepatitis C virus infection.

Persistent negative illness perceptions despite long-term biochemical control of acromegaly: novel application of the drawing test.

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Tiemensma, Jitske; Pereira, Alberto M; Romijn, Johannes A; Broadbent, Elizabeth; Biermasz, Nienke R; Kaptein, Adrian A

2015-05-01

Patients with acromegaly have persistent complaints despite long-term biochemical control. Drawings can be used to assess patients' perceptions about their disease. We aimed to explore the utility of the drawing test and its relation to illness perceptions and quality of life (QoL) in patients after long-term remission of acromegaly. A cross-sectional study was conducted to evaluate the utility of the drawing test. A total of 50 patients after long-term remission (mean±s.e.m., 16±1.2 years) of acromegaly were included in this study. Patients completed the drawing test (two retrospective drawings of their body perception before acromegaly and during the active phase of acromegaly, and one drawing on the current condition after long-term remission), Illness Perception Questionnaire-Revised, Physical Symptom Checklist, EuroQoL-5D, and AcroQoL. Patients perceived a dramatic change in body size during the active state of the disease compared with the healthy state before the awareness of acromegaly. Patients reported that their body did not completely return to the original proportions after long-term remission. In addition, larger drawings indicated more negative consequences (Pdrawings also indicated more impaired QoL, especially disease-specific QoL (all Pdrawing test, illness perceptions, and QoL. The drawing test appears to be a novel and relatively easy tool to assess the perception of patients after long-term remission of acromegaly. The assessment of drawings may enable health care providers to appreciate the perceptions of patients with long-term remission of acromegaly, and enable discussion of symptoms and remission. © 2015 European Society of Endocrinology.

Evaluating and ranking threats to the long-term persistence of polar bears

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Atwood, Todd C.; Marcot, Bruce G.; Douglas, David C.; Amstrup, Steven C.; Rode, Karyn D.; Durner, George M.; Bromaghin, Jeffrey F.

2015-01-01

The polar bear (Ursus maritimus) was listed as a globally threatened species under the U.S. Endangered Species Act (ESA) in 2008, mostly due to the significant threat to their future population viability from rapidly declining Arctic sea ice. A core mandate of the ESA is the development of a recovery plan that identifies steps to maintain viable populations of a listed species. A substantive evaluation of the relative influence of putative threats to population persistence is helpful to recovery planning. Because management actions must often be taken in the face of substantial information gaps, a formalized evaluation hypothesizing potential stressors and their relationships with population persistence can improve identification of relevant conservation actions. To this end, we updated a Bayesian network model previously used to forecast the future status of polar bears worldwide. We used new information on actual and predicted sea ice loss and polar bear responses to evaluate the relative influence of plausible threats and their mitigation through management actions on the persistence of polar bears in four ecoregions. We found that polar bear outcomes worsened over time through the end of the century under both stabilized and unabated greenhouse gas (GHG) emission pathways. Under the unabated pathway (i.e., RCP 8.5), the time it took for polar bear populations in two of four ecoregions to reach a dominant probability of greatly decreased was hastened by about 25 years. Under the stabilized GHG emission pathway (i.e., RCP 4.5), where GHG emissions peak around the year 2040, the polar bear population in the Archipelago Ecoregion of High Arctic Canada never reached a dominant probability of greatly decreased, reinforcing earlier suggestions of this ecoregion’s potential to serve as a long-term refugium. The most influential drivers of adverse polar bear outcomes were declines to overall sea ice conditions and to the marine prey base. Improved sea ice conditions

Human T cell aging and the impact of persistent viral infections

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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.

Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD.

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Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsoyr, Ole; Faraone, Stephen V; Peleikis, Dawn E

2014-06-01

Few studies have examined the impact of childhood attention deficit hyperactivity disorder (ADHD) symptoms on adult ADHD functional outcomes. To address this issue dimensionally, ADHD symptoms in childhood and adulthood and their relation to educational deficits and work disability are studied in a clinical sample of adult patients with previously untreated ADHD. About 250 adults diagnosed systematically with ADHD according to DSM-IV were prospectively recruited. Primary outcomes were high school dropout and being out of the work last year. Childhood ADHD symptoms, sex differences, comorbidities of other mental disorders, and adult ADHD symptoms were examined by historical data, clinician interviews, and questionnaires. High levels of ADHD symptom severity in childhood were related to dropping out of high school [odds ratio (OR) = 3.0], as were higher numbers of hyperactive-impulsive symptoms in childhood. Significantly, more women than men were long-term work disabled (OR = 2.0). After adjusting for age and gender, persisting high levels of ADHD inattention symptoms in adulthood (OR = 2.5), number of comorbid disorders, and particularly anxiety disorders were significantly related to long-term work disability. Childhood hyperactive-impulsive symptoms and overall severity of childhood ADHD symptoms were associated with high school dropout rates; however, persisting ADHD inattention symptoms and comorbid mental disorders in adulthood were more correlated to occupational impairment. These findings underline proposals for studies on early recognition and interventions for ADHD and psychiatric comorbidity. They further suggest that inattentive symptoms be a focus of adult ADHD treatment and that workplace interventions be considered to prevent long-term work disability.

Comprehensive analysis of LANA interacting proteins essential for viral genome tethering and persistence.

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Subhash C Verma

Full Text Available Kaposi's sarcoma associated herpesvirus is tightly linked to multiple human malignancies including Kaposi's sarcoma (KS, Primary Effusion Lymphoma (PEL and Multicentric Castleman's Disease (MCD. KSHV like other herpesviruses establishes life-long latency in the infected host by persisting as chromatin and tethering to host chromatin through the virally encoded protein Latency Associated Nuclear Antigen (LANA. LANA, a multifunctional protein, is capable of binding to a large number of cellular proteins responsible for transcriptional regulation of various cellular and viral pathways involved in blocking cell death and promoting cell proliferation. This leads to enhanced cell division and replication of the viral genome, which segregates faithfully in the dividing tumor cells. The mechanism of genome segregation is well known and the binding of LANA to nucleosomal proteins, throughout the cell cycle, suggests that these interactions play an important role in efficient segregation. Various biochemical methods have identified a large number of LANA binding proteins, including histone H2A/H2B, histone H1, MeCP2, DEK, CENP-F, NuMA, Bub1, HP-1, and Brd4. These nucleosomal proteins may have various functions in tethering of the viral genome during specific phases of the viral life cycle. Therefore, we performed a comprehensive analysis of their interaction with LANA using a number of different assays. We show that LANA binds to core nucleosomal histones and also associates with other host chromatin proteins including histone H1 and high mobility group proteins (HMGs. We used various biochemical assays including co-immunoprecipitation and in-vivo localization by split GFP and fluorescence resonance energy transfer (FRET to demonstrate their association.

Persistent muscle fiber regeneration in long term denervation. Past, present, future

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Ugo Carraro

2015-03-01

Full Text Available Despite the ravages of long term denervation there is structural and ultrastructural evidence for survival of muscle fibers in mammals, with some fibers surviving at least ten months in rodents and 3-6 years in humans. Further, in rodents there is evidence that muscle fibers may regenerate even after repeated damage in the absence of the nerve, and that this potential is maintained for several months after denervation. While in animal models permanently denervated muscle sooner or later loses the ability to contract, the muscles may maintain their size and ability to function if electrically stimulated soon after denervation. Whether in mammals, humans included, this is a result of persistent de novo formation of muscle fibers is an open issue we would like to explore in this review. During the past decade, we have studied muscle biopsies from the quadriceps muscle of Spinal Cord Injury (SCI patients suffering with Conus and Cauda Equina syndrome, a condition that fully and irreversibly disconnects skeletal muscle fibers from their damaged innervating motor neurons. We have demonstrated that human denervated muscle fibers survive years of denervation and can be rescued from severe atrophy by home-based Functional Electrical Stimulation (h-bFES. Using immunohistochemistry with both non-stimulated and the h-bFES stimulated human muscle biopsies, we have observed the persistent presence of muscle fibers which are positive to labeling by an antibody which specifically recognizes the embryonic myosin heavy chain (MHCemb. Relative to the total number of fibers present, only a small percentage of these MHCemb positive fibers are detected, suggesting that they are regenerating muscle fibers and not pre-existing myofibers re-expressing embryonic isoforms. Although embryonic isoforms of acetylcholine receptors are known to be re-expressed and to spread from the end-plate to the sarcolemma of muscle fibers in early phases of muscle denervation, we suggest

EXAMINATION OF ELECTROPHYSIOLOGICAL PARAMETERS OF THE ATRIUMS IN PATIENTS WITH LONG-TERM PERSISTENT FORM OF ATRIAL FIBRILLATION AND VALVULAR HEART DISEASE

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A. A. Kulikov

2017-01-01

Full Text Available The study objective is to examine electrophysiological parameters of atrial myocardium, characteristics of atrioventricular conduction, and potential factors affecting recurrent atrial fibrillation (AF in patients with persistent and long-term persistent forms of AF prior to the Labirynth IIIB surgery with single-step correction of valvular heart disease.Materials and methods. The study included 100 adults (48 men, 52 women with persistent and long-term persistent forms of AF and different valvular heart diseases. Mean patient age was 59 years. Mean AF duration was 4 years. All patients were prescribed antiarrhythmic therapy but it proved ineffective. In 15 % of patients, restoration of the sinus rhythm was attempted through electrical cardioversion but long-term control of the sinus rhythm wasn’t achieved. All patients were diagnosed with organic pathology of the mitral valve. Also, in 80 % of patients, relative insufficiency of the tricuspid valve was detected. Chronic heart failure functional class per NYHA was III. Size of the left atrium was 5 cm, mean left ventricular ejection fraction was 61 %. All patients underwent electrical cardioversion. After successful restoration of the sinus rhythm, endocardial electrophysiology study (EES of the heart was performed. Then, correction of valvular pathologies and the Labyrinth IIIB surgery were performed. Results. Examination of refractoriness of different parts of the atriums has shown that effective refractory period (ERP of the atrioventricular node was minimal compared to other parts of the atriums. Maximal ERP duration was observed in the upper part of the right atrium. Therefore, in patients with long history of AF, heterogeneity of atrial myocardium ERP duration is observed. In 17 % of patients, atrial vulnerability was detected. The area of atrial vulnerability was always associated with ERP. Its duration in patients with atrial vulnerability was significantly higher.Conclusion. Long-term

Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

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Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming; Eliceiri, Kevin W; Ahlquist, Paul; Sherer, Nathan M

2017-02-01

Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. © 2017 Pocock et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication 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).

Host resistance, population structure and the long-term persistence of bubonic plague: contributions of a modelling approach in the Malagasy focus.

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Fanny Gascuel

Full Text Available Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i endemicity is favoured by intermediate host population sizes, (ii in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar.

Host Resistance, Population Structure and the Long-Term Persistence of Bubonic Plague: Contributions of a Modelling Approach in the Malagasy Focus

Science.gov (United States)

Gascuel, Fanny; Choisy, Marc; Duplantier, Jean-Marc; Débarre, Florence; Brouat, Carine

2013-01-01

Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar. PMID:23675291

The effects of landscape modifications on the long-term persistence of animal populations.

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Jacob Nabe-Nielsen

Full Text Available BACKGROUND: The effects of landscape modifications on the long-term persistence of wild animal populations is of crucial importance to wildlife managers and conservation biologists, but obtaining experimental evidence using real landscapes is usually impossible. To circumvent this problem we used individual-based models (IBMs of interacting animals in experimental modifications of a real Danish landscape. The models incorporate as much as possible of the behaviour and ecology of four species with contrasting life-history characteristics: skylark (Alauda arvensis, vole (Microtus agrestis, a ground beetle (Bembidion lampros and a linyphiid spider (Erigone atra. This allows us to quantify the population implications of experimental modifications of landscape configuration and composition. METHODOLOGY/PRINCIPAL FINDINGS: Starting with a real agricultural landscape, we progressively reduced landscape complexity by (i homogenizing habitat patch shapes, (ii randomizing the locations of the patches, and (iii randomizing the size of the patches. The first two steps increased landscape fragmentation. We assessed the effects of these manipulations on the long-term persistence of animal populations by measuring equilibrium population sizes and time to recovery after disturbance. Patch rearrangement and the presence of corridors had a large effect on the population dynamics of species whose local success depends on the surrounding terrain. Landscape modifications that reduced population sizes increased recovery times in the short-dispersing species, making small populations vulnerable to increasing disturbance. The species that were most strongly affected by large disturbances fluctuated little in population sizes in years when no perturbations took place. SIGNIFICANCE: Traditional approaches to the management and conservation of populations use either classical methods of population analysis, which fail to adequately account for the spatial configurations

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

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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.

Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

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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.

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

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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.

Long-Term Persistence of Pesticides and TPs in Archived Agricultural Soil Samples and Comparison with Pesticide Application.

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Chiaia-Hernandez, Aurea C; Keller, Armin; Wächter, Daniel; Steinlin, Christine; Camenzuli, Louise; Hollender, Juliane; Krauss, Martin

2017-09-19

For polar and more degradable pesticides, not many data on long-term persistence in soil under field conditions and real application practices exist. To assess the persistence of pesticides in soil, a multiple-compound screening method (log K ow 1.7-5.5) was developed based on pressurized liquid extraction, QuEChERS and LC-HRMS. The method was applied to study 80 polar pesticides and >90 transformation products (TPs) in archived topsoil samples from the Swiss Soil Monitoring Network (NABO) from 1995 to 2008 with known pesticide application patterns. The results reveal large variations between crop type and field sites. For the majority of the sites 10-15 pesticides were identified with a detection rate of 45% at concentrations between 1 and 330 μg/kg dw in soil. Furthermore, TPs were detected in 47% of the cases where the "parent-compound" was applied. Overall, residues of about 80% of all applied pesticides could be detected with half of these found as TPs with a persistence of more than a decade.

Persistent, Long-term Cerebral White Matter Changes after Sports-Related Repetitive Head Impacts

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Bazarian, Jeffrey J.; Zhu, Tong; Zhong, Jianhui; Janigro, Damir; Rozen, Eric; Roberts, Andrew; Javien, Hannah; Merchant-Borna, Kian; Abar, Beau; Blackman, Eric G.

2014-01-01

Introduction Repetitive head impacts (RHI) sustained in contact sports are thought to be necessary for the long-term development of chronic traumatic encephalopathy (CTE). Our objectives were to: 1) characterize the magnitude and persistence of RHI-induced white matter (WM) changes; 2) determine their relationship to kinematic measures of RHI; and 3) explore their clinical relevance. Methods Prospective, observational study of 10 Division III college football players and 5 non-athlete controls during the 2011-12 season. All subjects underwent diffusion tensor imaging (DTI), physiologic, cognitive, and balance testing at pre-season (Time 1), post-season (Time 2), and after 6-months of no-contact rest (Time 3). Head impact measures were recorded using helmet-mounted accelerometers. The percentage of whole-brain WM voxels with significant changes in fractional anisotropy (FA) and mean diffusivity (MD) from Time 1 to 2, and Time 1 to 3 was determined for each subject and correlated to head impacts and clinical measures. Results Total head impacts for the season ranged from 431–1,850. No athlete suffered a clinically evident concussion. Compared to controls, athletes experienced greater changes in FA and MD from Time 1 to 2 as well as Time 1 to 3; most differences at Time 2 persisted to Time 3. Among athletes, the percentage of voxels with decreased FA from Time 1 to 2 was positively correlated with several helmet impact measures. The persistence of WM changes from Time 1 to 3 was also associated with changes in serum ApoA1 and S100B autoantibodies. WM changes were not consistently associated with cognition or balance. Conclusions A single football season of RHIs without clinically-evident concussion resulted in WM changes that correlated with multiple helmet impact measures and persisted following 6 months of no-contact rest. This lack of WM recovery could potentially contribute to cumulative WM changes with subsequent RHI exposures. PMID:24740265

Avian influenza H5N1 viral and bird migration networks in Asia

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Tian, Huaivu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

2015-01-01

The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.

Current strategies for non-pharmacological therapy of long-standing persistent atrial fibrillation

Directory of Open Access Journals (Sweden)

Teiichi Yamane, MD, PhD

2012-06-01

Full Text Available Non-pharmacological rhythm control of atrial fibrillation (AF is becoming increasingly important in our aging society. Advancement of catheter ablation techniques in the last decade has provided a cure for AF patients, with a nearly established efficiency for paroxysmal cases. However, since ablation of persistent/chronic AF cases is still challenging, early treatment of paroxysmal AF before transformation to the persistent/chronic form is mandatory. Although there is a consensus that pulmonary vein isolation is the first-line approach for ablation of long-standing persistent AF, similar to that for paroxysmal AF, there are still wide variations in the adjunctive approach to modify the atrial substrate of persistent AF (anatomical linear ablation, electrogram-based complex fractionated atrial electrogram ablation, ganglionated plexus ablation, etc.. Since data comparing the effectiveness of these adjunctive approaches are still lacking, large-scale controlled trials evaluating the effect of catheter ablation in diverse patient populations on a long-term basis are needed to establish the appropriate approach for long-standing persistent AF. Furthermore, the development of de novo ablation methods (new energies, new targets, etc. is expected to improve ablation outcome in patients with long-standing persistent AF.

Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

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Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

2011-01-01

Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

Effects of vaccination against viral haemorrhagic disease and myxomatosis on long-term mortality rates of European wild rabbits.

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Calvete, C; Estrada, R; Lucientes, J; Osacar, J J; Villafuerte, R

2004-09-25

The effects of vaccination against myxomatosis and viral haemorrhagic disease (VHD) on long-term mortality rates in European rabbits (Oryctolagus cuniculus) were studied from 1993 to 1996 by radiotracking a free-living population of wild rabbits. During the three months after immunisation, unvaccinated young rabbits weighing between 180 and 600 g were 13.6 times more likely to die than vaccinated young rabbits. In adult rabbits, vaccination did not significantly decrease mortality, mainly owing to the high proportion of rabbits which had previously been exposed to the antigens of both diseases. Compared with adult rabbits with natural antibodies to VHD, rabbits without these antibodies were 5.2 times more likely to die of VHD during annual outbreaks.

Persistent hepatitis virus infection and immune homeostasis

OpenAIRE

ZHOU Yun

2014-01-01

Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

Long-term use of antiplatelet drugs by stroke patients

DEFF Research Database (Denmark)

Ostergaard, Kamilla; Hallas, Jesper; Bak, Søren

2012-01-01

PURPOSE: Treatment with antiplatelet drugs is a key element of secondary stroke prevention. We investigated long-term antiplatelet drug use in stroke patients with a focus on non-persistence. METHODS: Population-based prescription register data were used to determine antiplatelet drug use...... the dosage of a previous prescription had run out, or within 180 days after discharge. Cox regression was used to identify risk factors for non-persistence. RESULTS: The cohort comprised 503 patients with ischaemic stroke discharged in 1999-2001. During follow-up (median 2.8 years, interquartile range 0......-persistent. Stroke severity was inversely associated with the risk of non-persistence [NIHSS score on admission 0-3 (reference); 4-6: hazard risk (HR) 0.87, 95 % confidence interval (CI) 0.61-1.25; 7+: HR 0.47, 95 % CI 0.29-0.74]. CONCLUSIONS: Long-term non-persistence with antiplatelet treatment was high and more...

Postpartum Engagement in HIV Care: An Important Predictor of Long-term Retention in Care and Viral Suppression.

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Adams, Joëlla W; Brady, Kathleen A; Michael, Yvonne L; Yehia, Baligh R; Momplaisir, Florence M

2015-12-15

Human immunodeficiency virus (HIV)-infected women are at risk of virologic failure postpartum. We evaluated factors influencing retention in care and viral suppression in postpartum HIV-infected women. We conducted a retrospective cohort analysis (2005-2011) of 695 deliveries involving 561 HIV-infected women in Philadelphia. Multivariable logistic regression evaluated factors, including maternal age, race/ethnicity, substance use, antiretroviral therapy during pregnancy, timing of HIV diagnosis, previous pregnancy with HIV, adequacy of prenatal care, and postpartum HIV care engagement (≥ 1 CD4 count or viral load [VL] test within 90 days of delivery), associated with retention in care (≥ 1 CD4 count or VL test in each 6-month interval of the period with ≥ 60 days between tests) and viral suppression (VL ≤ 200 copies/mL at the last measure in the period) at 1 and 2 years postpartum. Overall, 38% of women engaged in HIV care within 90 days postpartum; with 39% and 31% retained in care and virally suppressed, respectively, at 1 year postpartum, and 25% and 34% retained in care and virally suppressed, respectively, at 2 years postpartum. In multivariable analyses, women who engaged in HIV care within 90 days of delivery were more likely to be retained (adjusted odds ratio [AOR], 11.38; 95% confidence interval [CI], 7.74-16.68) and suppressed (AOR, 2.60 [95% CI, 1.82-3.73]) at 1 year postpartum. This association persisted in the second year postpartum for both retention (AOR, 6.19 [95% CI, 4.04-9.50]) and suppression (AOR, 1.40 [95% CI, 1.01-1.95]). The prevalence of postpartum HIV-infected women retained in care and maintaining viral suppression is low. Interventions seeking to engage women in care shortly after delivery have the potential to improve clinical outcomes. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Long-term effectiveness of localization studies and intraoperative parathormone monitoring in patients undergoing reoperative parathyroidectomy for persistent or recurrent hyperparathyroidism.

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Parikh, Punam P; Farra, Josefina C; Allan, Bassan J; Lew, John I

2015-07-01

Reoperative parathyroidectomy (RPTX) for persistent or recurrent hyperparathyroidism is associated with a high rate of operative failure. The long-term effectiveness of RPTX using localization studies and intraoperative parathormone monitoring (IPM) was examined. Retrospective analysis of prospectively collected data from patients undergoing targeted RPTX with IPM for persistent or recurrent hyperparathyroidism was performed. Persistent hyperparathyroidism was defined as elevated calcium and parathormone (PTH) levels above normal range less than 6 months after parathyroidectomy. Recurrent hyperparathyroidism was defined as elevated calcium and PTH levels greater than 6 months after successful parathyroidectomy. Sensitivity and positive predictive value (PPV) for sestamibi, surgeon-performed ultrasound, intraoperative PTH dynamics, and surgical outcomes were evaluated. Of the 1,064 patients, 69 patients underwent 72 RPTXs with localizing studies and IPM. Sestamibi (n = 69) had a sensitivity of 74% and a PPV of 83%, whereas surgeon-performed ultrasound (n = 38) had a sensitivity of 55% and a PPV of 76%. IPM had a sensitivity of 100% and a PPV of 98%. An intraoperative PTH drop greater than or equal to 50% was predictive of operative success (P < .01). Overall, operative success and recurrence were 94% and 1.4%, with a mean patient follow-up of 59 ± 12.8 months. RPTX can be performed in a targeted approach using preoperative localization studies and IPM, leading to a low rate of complications and a high rate of long-term operative success. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term dependence in exchange rates

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A. Karytinos

2000-01-01

Full Text Available The extent to which exchange rates of four major currencies against the Greek Drachma exhibit long-term dependence is investigated using a R/S analysis testing framework. We show that both classic R/S analysis and the modified R/S statistic if enhanced by bootstrapping techniques can be proven very reliable tools to this end. Our findings support persistence and long-term dependence with non-periodic cycles for the Deutsche Mark and the French Franc series. In addition a noisy chaos explanation is favored over fractional Brownian motion. On the contrary, the US Dollar and British Pound were found to exhibit a much more random behavior and lack of any long-term structure.

Host phylogeny determines viral persistence and replication in novel hosts.

Directory of Open Access Journals (Sweden)

Ben Longdon

2011-09-01

Full Text Available Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

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

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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.

Near-Infrared Quantum Cutting Long Persistent Luminescence

OpenAIRE

Zou, Zehua; Feng, Lin; Cao, Cheng; Zhang, Jiachi; Wang, Yuhua

2016-01-01

By combining the unique features of the quantum cutting luminescence and long persistent luminescence, we design a new concept called ?near-infrared quantum cutting long persistent luminescence (NQPL)?, which makes it possible for us to obtain highly efficient (>100%) near-infrared long persistent luminescence in theory. Guided by the NQPL concept, we fabricate the first NQPL phosphor Ca2Ga2GeO7:Pr3+,Yb3+. It reveals that both the two-step energy transfer of model (I) and the one-step energy ...

Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA.

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Lanford, Robert E; Feng, Zongdi; Chavez, Deborah; Guerra, Bernadette; Brasky, Kathleen M; Zhou, Yan; Yamane, Daisuke; Perelson, Alan S; Walker, Christopher M; Lemon, Stanley M

2011-07-05

Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.

The Persistence of Long Work Hours

OpenAIRE

Robert Drago; David Black; Mark Wooden

2005-01-01

Previous research hypothesizes that long working hours are related to consumerism, the ideal worker norm, high levels of human capital, and a high cost-of-job-loss. The authors test these hypotheses using panel data on working hours for an Australian sample of full-time employed workers. Analyses include a static cross-sectional model and a persistence model for long hours over time. The results suggest that long hours (50 or more hours in a usual week) are often persistent, and provide stron...

Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling.

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Yi, Jee Hyun; Zhang, JiaBao; Ko, Sang Yoon; Kwon, Huiyoung; Jeon, Se Jin; Park, Se Jin; Jung, Jiwook; Kim, Byung C; Lee, Young Choon; Kim, Dong Hyun; Ryu, Jong Hoon

2018-02-09

Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3β mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Akt blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3β blocked the natural decline in LTP. These results demonstrate that GSK-3β might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Akt/GSK-3β signaling.

Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis

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Lai, Tianwen; Wang, Shaobin; Xu, Zhiwei; Zhang, Chao; Zhao, Yun; Hu, Yue; Cao, Chao; Ying, Songmin; Chen, Zhihua; Li, Wen; Wu, Bin; Shen, Huahao

2015-01-01

Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i) systematically review the evidence regarding the long-term efficacy of omalizumab in patients with persistent uncontrolled allergic asthma, and to (ii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A comprehensive search for randomized controlled trials (RCTs; ≥52 weeks) was performed, and six studies met our final inclusion criteria (n = 2,749). Omalizumab was associated with significant improvements in quality of life and the Global Evaluation of Treatment Effectiveness. Omalizumab also allowed patients to completely withdraw from inhaled corticosteroid therapy and did not increase the overall incidence of adverse events. However, there was insufficient evidence that omalizumab reduced the incidence of exacerbations, and the cost-effectiveness of omalizumab varied across studies. Our data indicated that omalizumab use for at least 52 weeks in patients with persistent uncontrolled allergic asthma was accompanied by an acceptable safety profile, but it lacked effect on the asthma exacerbations. Use of omalizumab was associated with a higher cost than conventional therapy, but these increases may be cost-effective if the medication is used in patients with severe allergic asthma. PMID:25645133

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

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Gurbindo-Gutierrez Dolores

2006-01-01

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

Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

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Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

2016-07-01

Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Decoupling the short- and long-term behavior of stochastic volatility

DEFF Research Database (Denmark)

Bennedsen, Mikkel; Lunde, Asger; Pakkanen, Mikko

behavior) from long memory and persistence (long-term behavior) in a simple and parsimonious way, which allows us to successfully model volatility at all intraday time scales. Our prime model is based on the so-called Brownian semistationary process and we derive a number of theoretical properties...... measures of close to two thousand individual US equities, we find that both roughness and persistence appear to be universal properties of volatility. Inspired by the empirical findings, we introduce a new class of continuous-time stochastic volatility models, capable of decoupling roughness (short-term...

Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

DEFF Research Database (Denmark)

Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

2013-01-01

Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...

Case Report: Emergence of bovine viral diarrhea virus persistently infected calves in a closed herd

Science.gov (United States)

Bovine viral diarrhea virus (BVDV) continues to have significant economic impact on the cattle industry worldwide. The virus is primarily maintained in the cattle population due to persistently infected animals. Herd surveillance along with good vaccination programs and biosecurity practices are the...

Altered duodenal microbiota composition in celiac disease patients suffering from persistent symptoms on a long-term gluten-free diet.

Science.gov (United States)

Wacklin, Pirjo; Laurikka, Pilvi; Lindfors, Katri; Collin, Pekka; Salmi, Teea; Lähdeaho, Marja-Leena; Saavalainen, Päivi; Mäki, Markku; Mättö, Jaana; Kurppa, Kalle; Kaukinen, Katri

2014-12-01

A significant fraction of celiac disease patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD) and normalized small bowel mucosa. The commonly suggested reasons, such as inadvertent gluten-intake or presence of other gastrointestinal disease, do not explain the symptoms in all these patients. Recently, alterations in intestinal microbiota have been associated with autoimmune disorders, including celiac disease. This led us to test a hypothesis that abnormal intestinal microbiota may be associated with persisting gastrointestinal symptoms in treated celiac disease patients. Duodenal microbiota was analyzed in 18 GFD-treated patients suffering from persistent symptoms and 18 treated patients without symptoms by 16S rRNA gene pyrosequencing. The celiac disease patients had been following a strict GFD for several years and had restored small bowel mucosa and negative celiac autoantibodies. Their symptoms on GFD were assessed with Gastrointestinal Symptom Rating Scale. The results of several clustering methods showed that the treated celiac disease patients with persistent symptoms were colonized by different duodenal microbiota in comparison with patients without symptoms. The treated patients with persistent symptoms had a higher relative abundance of Proteobacteria (P=0.04) and a lower abundance of Bacteroidetes (P=0.01) and Firmicutes (P=0.05). Moreover, their microbial richness was reduced. The results indicated intestinal dysbiosis in patients with persistent symptoms even while adhering to a strict GFD. Our findings indicate that dysbiosis of microbiota is associated with persistent gastrointestinal symptoms in treated celiac disease patients and open new possibilities to treat this subgroup of patients.

Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder.

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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.

Long-term follow-up of patients treated for psychotic symptoms that persist after stopping illicit drug use.

Science.gov (United States)

Deng, Xianhua; Huang, Zhibiao; Li, Xuewu; Li, Yi; Wang, Yi; Wu, Dongling; Gao, Beiling; Yang, Xi

2012-10-01

The long-term outcome of patients diagnosed with drug-induced psychotic disorders in China is unknown. Assess the course of illness and severity of psychiatric symptoms in patients previously admitted to a psychiatric hospital for treatment of psychotic symptoms that were induced by the use of illicit drugs. Patients with psychotic symptoms at the time of their first psychiatric admission who had used illicit drugs in the month prior to admission were followed up 13 to 108 months after admission. Patients and coresident family members were interviewed about post-discharge drug use and psychotic symptoms. The 258 identified patients were primarily young, unemployed males whose most common drug of abuse was methamphetamines and who had been abusing drugs for an average of 7 years at the time of admission. Among these patients 189 (73%) were located and reinterviewed; 168 (89%) had restarted illicit drug use and 25 (13%) had required rehospitalization over the follow-up period. In 114 patients (60%) the psychotic symptoms resolved in less than 1 month after stopping the drugs, in 56 (30%) the symptoms persisted for 1 to 6 months, and in 19 (10%) the symptoms persisted for longer than 6 months (in 8 of these the diagnosis had changed to schizophrenia). Compared to the other two groups, patients whose symptoms persisted more than 6 months were more likely to have a family history of mental illness, an earlier age of onset and a longer duration of drug abuse prior to the index admission; they were also more likely to have been re-hospitalized during the follow-up period and to have psychotic symptoms at the time of follow-up. Most patients with substance-induced psychotic disorders in our sample had a good long-term prognosis but those who started illegal drug use early, used drugs for prolonged periods, or had a family history of psychiatric illnesses were more likely to develop a chronic psychosis. Further prospective studies are needed to determine the relationship of

Long-term monitoring of persistent organic pollutants (POPs at the Norwegian Troll station in Dronning Maud Land, Antarctica

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R. Kallenborn

2013-07-01

Full Text Available A first long-term monitoring of selected persistent organic pollutants (POPs in Antarctic air has been conducted at the Norwegian research station Troll (Dronning Maud Land. As target contaminants 32 PCB congeners, α- and γ-hexachlorocyclohexane (HCH, trans- and cis-chlordane, trans- and cis-nonachlor, p,p'- and o,p-DDT, DDD, DDE as well as hexachlorobenzene (HCB were selected. The monitoring program with weekly samples taken during the period 2007–2010 was coordinated with the parallel program at the Norwegian Arctic monitoring site (Zeppelin mountain, Ny-Ålesund, Svalbard in terms of priority compounds, sampling schedule as well as analytical methods. The POP concentration levels found in Antarctica were considerably lower than Arctic atmospheric background concentrations. Similar to observations for Arctic samples, HCB is the predominant POP compound, with levels of around 22 pg m−3 throughout the entire monitoring period. In general, the following concentration distribution was found for the Troll samples analyzed: HCB > Sum HCH > Sum PCB > Sum DDT > Sum chlordanes. Atmospheric long-range transport was identified as a major contamination source for POPs in Antarctic environments. Several long-range transport events with elevated levels of pesticides and/or compounds with industrial sources were identified based on retroplume calculations with a Lagrangian particle dispersion model (FLEXPART.

Long-term monitoring of persistent organic pollutants (POPs) at the Norwegian Troll station in Dronning Maud Land, Antarctica

Science.gov (United States)

Kallenborn, R.; Breivik, K.; Eckhardt, S.; Lunder, C. R.; Manø, S.; Schlabach, M.; Stohl, A.

2013-07-01

A first long-term monitoring of selected persistent organic pollutants (POPs) in Antarctic air has been conducted at the Norwegian research station Troll (Dronning Maud Land). As target contaminants 32 PCB congeners, α- and γ-hexachlorocyclohexane (HCH), trans- and cis-chlordane, trans- and cis-nonachlor, p,p'- and o,p-DDT, DDD, DDE as well as hexachlorobenzene (HCB) were selected. The monitoring program with weekly samples taken during the period 2007-2010 was coordinated with the parallel program at the Norwegian Arctic monitoring site (Zeppelin mountain, Ny-Ålesund, Svalbard) in terms of priority compounds, sampling schedule as well as analytical methods. The POP concentration levels found in Antarctica were considerably lower than Arctic atmospheric background concentrations. Similar to observations for Arctic samples, HCB is the predominant POP compound, with levels of around 22 pg m-3 throughout the entire monitoring period. In general, the following concentration distribution was found for the Troll samples analyzed: HCB > Sum HCH > Sum PCB > Sum DDT > Sum chlordanes. Atmospheric long-range transport was identified as a major contamination source for POPs in Antarctic environments. Several long-range transport events with elevated levels of pesticides and/or compounds with industrial sources were identified based on retroplume calculations with a Lagrangian particle dispersion model (FLEXPART).

Influenza a virus migration and persistence in North American wild birds.

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Justin Bahl

Full Text Available Wild birds have been implicated in the emergence of human and livestock influenza. The successful prediction of viral spread and disease emergence, as well as formulation of preparedness plans have been hampered by a critical lack of knowledge of viral movements between different host populations. The patterns of viral spread and subsequent risk posed by wild bird viruses therefore remain unpredictable. Here we analyze genomic data, including 287 newly sequenced avian influenza A virus (AIV samples isolated over a 34-year period of continuous systematic surveillance of North American migratory birds. We use a Bayesian statistical framework to test hypotheses of viral migration, population structure and patterns of genetic reassortment. Our results reveal that despite the high prevalence of Charadriiformes infected in Delaware Bay this host population does not appear to significantly contribute to the North American AIV diversity sampled in Anseriformes. In contrast, influenza viruses sampled from Anseriformes in Alberta are representative of the AIV diversity circulating in North American Anseriformes. While AIV may be restricted to specific migratory flyways over short time frames, our large-scale analysis showed that the long-term persistence of AIV was independent of bird flyways with migration between populations throughout North America. Analysis of long-term surveillance data provides vital insights to develop appropriately informed predictive models critical for pandemic preparedness and livestock protection.

Viral Small-RNA Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection

OpenAIRE

Zografidis, Aris; Van Nieuwerburgh, Filip; Kolliopoulou, Anna; Apostolou-Karampelis, Konstantinos; Head, Steven R.; Deforce, Dieter; Smagghe, Guy; Swevers, Luc

2015-01-01

The lepidopteran innate immune response against RNA viruses remains poorly understood, while in other insects several studies have highlighted an essential role for the exo-RNAi pathway in combating viral infection. Here, by using deep-sequencing technology for viral small-RNA (vsRNA) assessment, we provide evidence that exo-RNAi is operative in the silkworm Bombyx mori against both persistent and pathogenic infection of B. mori cytoplasmic polyhedrosis virus (BmCPV) which is characterized by...

Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency.

Science.gov (United States)

Barat, Corinne; Proust, Alizé; Deshiere, Alexandre; Leboeuf, Mathieu; Drouin, Jean; Tremblay, Michel J

2018-02-21

The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4 + T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary. We first demonstrate that the diminished HIV-1 production in a proliferating astrocyte culture is due to a reduced proliferative capacity of virus-infected cells compared with uninfected astrocytes. In contrast, infection of non-proliferating astrocytes led to a robust HIV-1 infection that was sustained for over 60 days. To identify astrocytes latently infected with HIV-1, we designed a new dual-color reporter virus called NL4.3 eGFP-IRES-Crimson that is fully infectious and encodes for all viral proteins. Although we detected a small fraction of astrocytes carrying silent HIV-1 proviruses, we did not observe any reactivation using various LRAs and even strong inducers such as tumor necrosis factor, thus suggesting that these proviruses were either not transcriptionally competent or in a state of deep latency. Our findings imply that astrocytes might not constitute a latent reservoir per se but that relentless virus production by this brain cell population could contribute to the neurological disorders seen in HIV-1-infected persons subjected to combination antiretroviral therapy. © 2018 Wiley Periodicals, Inc.

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.

Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion

Science.gov (United States)

Cook, R. Frank; Eberth, John; Chelvarajan, R. Lakshman; Artiushin, Sergey; Timoney, Peter J.

2016-01-01

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001) and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and Eq

Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion.

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Sanjay Sarkar

2016-12-01

Full Text Available Equine arteritis virus (EAV is the causative agent of equine viral arteritis (EVA, a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10-70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16 that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1 having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001 and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence in the male reproductive tract. EqCXCL16Sa and

Long memory and changing persistence

DEFF Research Database (Denmark)

Kruse, Robinson; Sibbertsen, Philipp

We study the empirical behaviour of semi-parametric log-periodogram estimation for long memory models when the true process exhibits a change in persistence. Simulation results confirm theoretical arguments which suggest that evidence for long memory is likely to be found. A recently proposed test...... by Sibbertsen and Kruse (2009) is shown to exhibit noticeable power to discriminate between long memory and a structural change in autoregressive parameters....

Comparison of ‘HoBi’-like viral populations among persistent infected calves generated under experimental conditions and to inoculum virus

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Like other members from the Pestivirus genus, ‘HoBi’-like pestiviruses cause economic losses for cattle producers due to both acute and persistent infections. Pestivirus exist as quasispecies (swarms of individual viruses) in persistently infected (PI) animals leading to viral populations that are m...

Long-term outcome following splenectomy for chronic and persistent immune thrombocytopenia (ITP) in adults and children : Splenectomy in ITP.

Science.gov (United States)

Ahmed, Rayaz; Devasia, Anup J; Viswabandya, Auro; Lakshmi, Kavitha M; Abraham, Aby; Karl, Sampath; Mathai, John; Jacob, Paul M; Abraham, Deepak; Srivastava, Alok; Mathews, Vikram; George, Biju

2016-09-01

The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29 years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2 %) including CR in 74.4 % at a median time of 1 day (range 1-54). Infections following splenectomy were reported in 16 %. Deaths related to post splenectomy sepsis occurred in 1.57 % and major bleeding in 0.78 %. At median follow-up of 54.3 months (range 1-290), 178 (70.1 %) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 ± 1.2 % and 94.9 ± 2.1 %, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9 % and 71.0 + 3.9 %, respectively. Splenectomy is associated with long-term remission rates of >70 % in chronic or persistent ITP.

Implementation of immunohistochemistry on frozen ear notch tissue samples in diagnosis of bovine viral diarrhea virus in persistently infected cattle

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Bedeković Tomislav

2011-12-01

Full Text Available Abstract Background Bovine viral diarrhea is a contagious disease of domestic and wild ruminants and one of the most economically important diseases in cattle. Bovine viral diarrhea virus belongs to the genus Pestivirus, within the family Flaviviridae. The identification and elimination of the persistently infected animals from herds is the initial step in the control and eradication programs. It is therefore necessary to have reliable methods for diagnosis of bovine viral diarrhea virus. One of those methods is immunohistochemistry. Immunohistochemistry on formalin fixed, paraffin embedded tissue is a routine technique in diagnosis of persistently infected cattle from ear notch tissue samples. However, such technique is inappropriate due to complicated tissue fixation process and it requires more days for preparation. On the contrary, immunohistochemistry on frozen tissue was usually applied on organs from dead animals. In this paper, for the first time, the imunohistochemistry on frozen ear notch tissue samples was described. Findings Seventeen ear notch tissue samples were obtained during the period 2008-2009 from persistently infected cattle. Samples were fixed in liquid nitrogen and stored on -20°C until testing. Ear notch tissue samples from all persistently infected cattle showed positive results with good section quality and possibility to determinate type of infected cells. Conclusions Although the number of samples was limited, this study indicated that immunohistochemistry on formalin fixed paraffin embedded tissue can be successfully replaced with immunohistochemistry on frozen ear notch tissue samples in diagnosis of persistently infected cattle.

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

OpenAIRE

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

2011-01-01

It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memo...

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.

Persistent hyperparathyroidism as a risk factor for long-term graft failure: the need to discuss indication for parathyroidectomy.

Science.gov (United States)

Araujo, Maria Júlia Correia Lima Nepomuceno; Ramalho, Janaina Almeida Mota; Elias, Rosilene Motta; Jorgetti, Vanda; Nahas, William; Custodio, Melani; Moysés, Rosa M A; David-Neto, Elias

2018-01-10

Although a successful kidney transplant (KTx) improves most of the mineral and bone disorders (MBD) produced by chronic kidney disease (CKD), hyperparathyroidism may persist (pHPT). Current guidelines recommend parathyroidectomy if serum parathormone is persistently elevated 1 year after KTx, because pHPT has been recently associated with poor graft outcomes. However, whether patients with pHPT and adequate renal function are at risk for long-term graft failure is unknown. Longitudinal follow-up of 911 adults submitted to KTx between January 2005 and December 2014, with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min 1 year after surgery. Clinical and laboratory data were collected from electronic database. Graft failure was defined as return to dialysis. Overall, 62% of the patients were classified as having pHPT 1 year after KTx. After a mean follow-up time of 47 months, there were 59 graft failures (49 in pHPT and 10 in non-pHPT group, P = .003). At last follow-up, death-censored graft survival was lower in the pHPT group (P = .009), even after adjustment for age at KTx, donor age, donor type, acute rejection, parathyroidectomy, and eGFR at 1 year after transplantation (odds ratio [OR] 1.99; 1.004-3.971; P = .049). A PTH of 150 pg/mL at 6 months was the best cutoff to predict pHPT at 1 year (specificity = 92.1%). Having pHPT after a successful KTx increases the long-term risk of death-censored graft failure. This result highlights the need for better recognition and management of CKD-MBD before and during the first year after KTx, and opens a discussion on the more appropriate timing to perform parathyroidectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

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...

Viral persistence in surface and drinking water: Suitability of PCR pre-treatment with intercalating dyes.

Science.gov (United States)

Prevost, B; Goulet, M; Lucas, F S; Joyeux, M; Moulin, L; Wurtzer, S

2016-03-15

After many outbreaks of enteric virus associated with consumption of drinking water, the study of enteric viruses in water has increased significantly in recent years. In order to better understand the dynamics of enteric viruses in environmental water and the associated viral risk, it is necessary to estimate viral persistence in different conditions. In this study, two representative models of human enteric viruses, adenovirus 41 (AdV 41) and coxsackievirus B2 (CV-B2), were used to evaluate the persistence of enteric viruses in environmental water. The persistence of infectious particles, encapsidated genomes and free nucleic acids of AdV 41 and CV-B2 was evaluated in drinking water and surface water at different temperatures (4 °C, 20 °C and 37 °C). The infectivity of AdV 41 and CV-B2 persisted for at least 25 days, whatever the water temperature, and for more than 70 days at 4 °C and 20 °C, in both drinking and surface water. Encapsidated genomes persisted beyond 70 days, whatever the water temperature. Free nucleic acids (i.e. without capsid) also were able to persist for at least 16 days in drinking and surface water. The usefulness of a detection method based on an intercalating dye pre-treatment, which specifically targets preserved particles, was investigated for the discrimination of free and encapsidated genomes and it was compared to virus infectivity. Further, the resistance of AdV 41 and CV-B2 against two major disinfection treatments applied in drinking water plants (UV and chlorination) was evaluated. Even after the application of UV rays and chlorine at high doses (400 mJ/cm(2) and 10 mg.min/L, respectively), viral genomes were still detected with molecular biology methods. Although the intercalating dye pre-treatment had little use for the detection of the effects of UV treatment, it was useful in the case of treatment by chlorination and less than 1 log10 difference in the results was found as compared to the infectivity measurements

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....

Long-Term Persistency of Abnormal Heart Rate Variability following Long NICU Stay and Surgery at Birth

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Mélanie Morin

2014-01-01

Full Text Available Preterm birth is associated with painful procedures during the neonatal intensive care unit (NICU stay. Full-term newborns can also experience pain, following surgery. These procedures can have long-lasting consequences. It has been shown that children born preterm show pain responses and cardiac alterations. This study aimed to explore the heart rate reactivity to pain in 107 subjects born either preterm or full-term who were between 7 and 25 years old at testing. We also evaluated the effect of pain experienced at birth, as represented by a longer NICU stay, time under ventilation, and surgery at birth. Participants were asked to immerse their right forearm in 10°C water for 2 minutes. Electrocardiograms were recorded at baseline and during the immersion procedure. Full-term subjects showed a stable increase in heart rate throughout the procedure, whereas preterm ones showed a strong increase at the beginning, which decreased over time. Also, preterm and full-term subjects who experienced pain at birth showed higher resting heart rate, stronger sympathetic activity, and lower cardiac vagal activity. Our study demonstrated a long-term impact of a long NICU stay and surgery at birth on cardiac autonomic activity. This could lead to impaired reactions to pain or stress in later life.

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

Science.gov (United States)

Ramirez-Carvajal, Lisbeth; Pauszek, Steven J; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S; Stockwell, Timothy B; Rodriguez, Luis L

2018-01-01

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

Directory of Open Access Journals (Sweden)

Lisbeth Ramirez-Carvajal

Full Text Available Foot-and-mouth disease (FMD is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

Long - Memory Persistence in African Stock Markets

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Emmanuel Numapau Gyamfi

2016-05-01

Full Text Available Emerging stock markets are said to become efficient with time. This study seeks to investigate this assertion by analyzing long - memory persistence in 8 African stock markets covering the period from 28 August 2000 to 28 August 2015. The Hurst exponent is used as our efficiency measure which is evaluated by the Detrended Fluctuation Analysis (DFA. Our findings show strong evidence of long - memory persistence in the markets studied therefore violating the weak - form Efficient Market Hypothesis (EMH.

Haloperidol for long-term aggression in psychosis.

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Khushu, Abha; Powney, Melanie J

2016-11-27

Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression. To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis. We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015). We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression. One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study

The existence and persistence of long work hours

OpenAIRE

Drago, Robert William; Black, David; Wooden, Mark

2005-01-01

Previous research hypothesizes that long working hours are related to consumerism, the ideal worker norm, high levels of human capital, and a high cost-of-job-loss. The authors test these hypotheses using panel data on working hours for an Australian sample of full-time employed workers. Analyses include a static cross-sectional model and a persistence model for long hours over time. The results suggest that long hours (50 or more hours in a usual week) are often persistent, and provide stron...

Long-term persistence of quality improvements for an intensive care unit communication initiative using the VALUE strategy.

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Wysham, Nicholas G; Mularski, Richard A; Schmidt, David M; Nord, Shirley C; Louis, Deborah L; Shuster, Elizabeth; Curtis, J Randall; Mosen, David M

2014-06-01

Communication in the intensive care unit (ICU) is an important component of quality ICU care. In this report, we evaluate the long-term effects of a quality improvement (QI) initiative, based on the VALUE communication strategy, designed to improve communication with family members of critically ill patients. We implemented a multifaceted intervention to improve communication in the ICU and measured processes of care. Quality improvement components included posted VALUE placards, templated progress note inclusive of communication documentation, and a daily rounding checklist prompt. We evaluated care for all patients cared for by the intensivists during three separate 3 week periods, pre, post, and 3 years following the initial intervention. Care delivery was assessed in 38 patients and their families in the pre-intervention sample, 27 in the post-intervention period, and 41 in follow-up. Process measures of communication showed improvement across the evaluation periods, for example, daily updates increased from pre 62% to post 76% to current 84% of opportunities. Our evaluation of this quality improvement project suggests persistence and continued improvements in the delivery of measured aspects of ICU family communication. Maintenance with point-of-care-tools may account for some of the persistence and continued improvements. Copyright © 2014 Elsevier Inc. All rights reserved.

Long term follow up in hemodialysis patients with parathyroidectomy

International Nuclear Information System (INIS)

Alvarez, A.; Petraglia, A.; Caorsi, H.; Mazzuchi, N.; Olaizola, I.; Acuna, G.; Fajardo, L.; Ambrosoni, P.; Morelli, R.

1998-01-01

A retrospective study was performed in 41 patients, in chronic hemodialysis with severe hyperparathyroidism (HPT), who underwent surgery during time period from 1985 to 1997. 22 females, 19 males, aged 50 and 14 years, with PTHI 1345 and 604 pg/ml were followed up 32 and 22 months. Three surgical methods we evaluated: group I) total para thyroidectomy(PTX) with Implants(n=24); group II) subtotal PTX(n=14) and group III) total PTX(n=3). It considered recurrence of HPT when PTH levels were higher than upper range of normal, after 6 months post surgery. persistence was defined when there was no standardization of PTH levels. In group I, 9 patients had normal parathyroid function, 7 had persistent hypoparathyroidism and had hyperparathyroidism (7 recurrences). Group II patients had parathyroid over function in 5 cases (4 persistence s), 5 were normal and 4 hypoparathyroidism. All patients of the third group had hypoparathyroidism. Long term normalization of parathyroid gland activity was achieved in one third of troduccion patients (34,1%) whereas 34,1% permanent hypoparathyroidism and 31,8% hyperparathyroidism. It found no differences in recurrence and histological subtype of parathyroid gland in the different groups. In conclusion, similar long term clinical results were obtained with the different groups. The surgical ideal treatment is controversial. We think that in the long run, the evolution of parathyroid status is mostly influenced by the persistence of uremic state rather than the type of surgery performed [es

The persistence of personal and social themes in context: Long- and short-term studies of students' scientific ideas

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Helldén, Gustav F.; Solomon, Joan

2004-11-01

In this paper we will examine the persistence of misconceptions. We used data from a longitudinal study of personal ideas in 24 students' thinking about ecological processes. The results show students often speaking about personal experiences dating from an early age, to which they had also referred in similar interviews conducted years before. These data are compared with results from a different study of middle school physics students' thinking about energy and steam engines. After the new learning had been successfull completed and assessed, old ideas returned. These findings are used to set up a theoretical basis for understanding the longitudinal results. Findings from memory studies are shown to explicate the long-term effects of the passage of time and prompts for the recall of scientific concepts.

Long-term complications in Hodgkin's lymphoma survivors.

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Kilickap, Saadettin; Barista, Ibrahim; Ulger, Sukran; Celik, Ismail; Selek, Ugur; Güllü, Ibrahim; Yildiz, Ferah; Kars, Ayse; Ozisik, Yavuz; Tekuzman, Gülten

2012-01-01

Background. Although patients with Hodgkin's lymphoma (HL) achieve prolonged survival, long-term complications are a major cause of morbidity and mortality among long-term survivors of HL. Methods. We retrospectively evaluated long-term complications in 336 HL survivors treated between January 1990 and January 2006 at the Department of Medical Oncology of the Hacettepe University Institute of Oncology who were >16 years old at presentation. All patients were regularly followed up every 3 months for the first 2 years after complete response, biannually for 3 years, and annually after 5 years. Results. Median follow-up was 8.5 years. The mean age (±SD) of the patients at the time of diagnosis was 35.7 ± 13.1 years. The male to female ratio was 61%/39%. During follow-up, 29 second malignancies (8.6%) were diagnosed in 28 patients with HL; 22 were solid tumors and 7 were hematological malignancies. Forty-seven (14.0%) of all patients with HL were found to have thyroid abnormalities. During follow-up, 54 (16.1%) patients developed cardiovascular complications. Overall, 29 (8.6%) patients developed late pulmonary toxicities. The cumulative number of chronic viral infections was 13 (3.9%). Conclusions. Long-term survivors of HL need to be properly followed up not only for disease control but also for evaluation of possible late morbidities to minimize the consequences.

The diagnosis and prevalence of persistent infection with bovine viral diarrhoea virus in South African feedlot cattle

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Thelma Meiring

2011-08-01

Full Text Available Bovine viral diarrhoea virus (BVDV infection is an important viral infection affecting the cattle industry today. The prevalence of this infection in South African feedlots is unknown. Ear notch biopsies were collected from chronic poor doers and animals that appeared unthrifty upon entering feedlots, as well as animals entering the hospital pen with respiratory disease for the first time. A total of 1690 samples were collected: 1074 from the former category and 616 from the latter. A routine immunohistochemistry staining protocol showed that 49 animals tested positive, of which 43 (4% came from the feedlot entry group and six (1% from the hospitalised group. The prevalence of persistently infected cattle from this selected, nonrandom sample entering six large South African feedlots was found to be 2.9%, which is higher than the international rule of thumb that 0.5% of all cattle entering feedlots are persistently infected. There was no clear correlation between persistent infection and respiratory disease. Serum samples were also collected when possible and 10 positive cases were found. Results from enzyme-linked immunosorbent assays for antigen and antibody performed on these sera correlated well with those from the immunohistochemistry staining method in six cases, but in four cases the animals tested falsely positive owing to nonspecific staining. Immunohistochemistry staining on ear notch biopsies is thus a reliable diagnostic method to identify persistently infected animals with BVDV, but the pathologist should be aware of nonspecific positive staining.

PRIMARY RESULTS OF LONG-TERM DYNAMIC MONITORING OF CHILDREN WITH BRONCHIAL ASTHMA OF UNCONTROLLED SEVERE PERSISTENT COURSE

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L. S. Namazova-Baranova

2016-01-01

Full Text Available Background. Patients registers help obtain the latest information about the clinical course of a disease, safety and effectiveness of the medical technology. Objective: Our aim was to analyze the efficiency and safety of omalizumab with children suffering from uncontrolled severe persistent bronchial asthma (BA according to the data of the developed register. Methods.  A register of patients with severe asthma of uncontrolled course receiving omalizumab in addition to basic therapy has been developed. Results. Results of treatment of 101 children aged 6–17 have been analyzed. The duration of therapy with omalizumab lasted from 1 to 85 months, with a median of 16 (10; 44 months. The drug was used in doses of 75 to 600 mg, with a median of 300 (225; 375 mg. The therapy with omalizumab allowed achieving a better control of the disease (AST test prior to start of therapy — 14 (11; 17 points, in 1 year — 20 (13; 25; p < 0,001; reduction of the volume of daily base therapy (prior to start of therapy, average dose of inhaled corticosteroids in terms of fluticasone was 629 ± 304 mg (n = 15, in 4 years — 524 ± 342 mg; p = 0.065; reduction of the number of aggravations and the need to use short-effectiv   2-agonists.  No adverse systemic effects of the introduction of genetically engineered biological drugs have been found. Conclusion. Register of patients with severe persistent asthma can be used as a tool for long-term  monitoring and integrated assessment of the efficiency and safety of therapy.

Optimal long-term contracting with learning

OpenAIRE

He, Zhiguo; Wei, Bin; Yu, Jianfeng; Gao, Feng

2016-01-01

We introduce uncertainty into Holmstrom and Milgrom (1987) to study optimal long-term contracting with learning. In a dynamic relationship, the agent's shirking not only reduces current performance but also increases the agent's information rent due to the persistent belief manipulation effect. We characterize the optimal contract using the dynamic programming technique in which information rent is the unique state variable. In the optimal contract, the optimal effort is front-loaded and decr...

Hepatitis B virus core antigen determines viral persistence in a C57BL/6 mouse model.

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Lin, Yi-Jiun; Huang, Li-Rung; Yang, Hung-Chih; Tzeng, Horng-Tay; Hsu, Ping-Ning; Wu, Hui-Lin; Chen, Pei-Jer; Chen, Ding-Shinn

2010-05-18

We recently developed a mouse model of hepatitis B virus (HBV) persistence, in which a single i.v. hydrodynamic injection of HBV DNA to C57BL/6 mice allows HBV replication and induces a partial immune response, so that about 20-30% of the mice carry HBV for more than 6 months. The model was used to identify the viral antigen crucial for HBV persistence. We knocked out individual HBV genes by introducing a premature termination codon to the HBV core, HBeAg, HBx, and polymerase ORFs. The specific-gene-deficient HBV mutants were hydrodynamically injected into mice and the HBV profiles of the mice were monitored. About 90% of the mice that received the HBcAg-mutated HBV plasmid exhibited high levels of hepatitis B surface antigenemia and maintained HBsAg expression for more than 6 months after injection. To map the region of HBcAg essential for viral clearance, we constructed a set of serial HBcAg deletion mutants for hydrodynamic injection. We localized the essential region of HBcAg to the carboxyl terminus, specifically to the 10 terminal amino acids (HBcAg176-185). The majority of mice receiving this HBV mutant DNA did not elicit a proper HBcAg-specific IFN-gamma response and expressed HBV virions for 6 months. These results indicate that the immune response triggered in mice by HBcAg during exposure to HBV is important in determining HBV persistence.

Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

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Nesrina eImami

2013-03-01

Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

Characterization of thymus-associated lymphoid depletion in bovine calves acutely or persistently infected with bovine viral diarrhea virus 1, bovine viral diarrhea 2 or HoBi-like pestivirus

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Viruses from recognized pestivirus species bovine viral diarrhea 1 (BVDV-1) and BVDV-2 and the proposed pestivirus species HoBi-like virus infect primarily cattle. Exposure of cattle to these viruses can lead to either acute or persistent infections depending on the timing and status of the animal ...

Testing hypotheses in an I(2) model with applications to the persistent long swings in the Dmk/$ rate

DEFF Research Database (Denmark)

Johansen, Søren; Juselius, Katarina; Frydman, Roman

long-term interest rates and two short-term interest rates over the 1975-1999 period. One important aim of the paper is to demonstrate that by structuring the data with the help of the I(2) model one can achieve a better understanding of the empirical regularities underlying the persistent swings...... components in the I(2) model is discussed at some length. Model specification and tests are illustrated with an empirical analysis of long and persistent swings in the foreign exchange market between Germany and USA. The data analyzed consist of nominal exchange rates, relative prices, US inflation rate, two...... in nominal exchange rates, typical in periods of floating exchange rates....

Postoperative CPAP use impacts long-term weight loss following bariatric surgery.

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Collen, Jacob; Lettieri, Christopher J; Eliasson, Arn

2015-03-15

Obstructive sleep apnea (OSA) is common among bariatric surgery candidates. After surgical weight loss, OSA frequently persists and untreated OSA can lead to weight gain. Long-term continuous positive airway pressure (CPAP) adherence is unclear and poor adherence may worsen weight loss outcomes. We sought to determine the impact of CPAP use on long-term weight-loss outcomes in a cohort of bariatric patients. Long-term observational study of bariatric surgery patients with OSA. Patients were evaluated with polysomnography preoperatively and one-year postoperatively. The cohort was again evaluated a mean of 7.2 years later to determine the relationship between long-term CPAP use and subsequent regain of weight. Twenty-four consecutive patients (aged 48.5 ± 9.4 years at time of surgery; 73% female) were included in the initial assessment, and long-term outcome data were available on 22 subjects. Persistent OSA was documented in 21 of 22 subjects (95%) one year postoperatively. Final evaluation occurred 7.2 ± 2.3 years following surgery. Weight (213.3 ± 39.1 to 235.3 ± 47.1 lb, p = 0.10) and BMI (32.5 ± 5.4 to 37.3 ± 8.2 kg/m(2), p = 0.03) increased in most (n = 19, 86.4%) from postoperative to final evaluation. CPAP use declined from 83.3% (preoperatively) to 38.1% (one year) and to 23.8% (final evaluation). BMI increased among those not using CPAP at long-term follow-up compared to those with continued CPAP use (6.8% v -1.8%, p = 0.05). In our cohort of bariatric patients with OSA, long-term adherence to CPAP therapy was poor, and non-adherence was associated with weight gain. Ongoing follow-up of OSA in this population may help to preserve initial achievements after surgical weight loss. © 2014 American Academy of Sleep Medicine.

Effect of genomic long-range correlations on DNA persistence length: from theory to single molecule experiments.

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Moukhtar, Julien; Faivre-Moskalenko, Cendrine; Milani, Pascale; Audit, Benjamin; Vaillant, Cedric; Fontaine, Emeline; Mongelard, Fabien; Lavorel, Guillaume; St-Jean, Philippe; Bouvet, Philippe; Argoul, Françoise; Arneodo, Alain

2010-04-22

Sequence dependency of DNA intrinsic bending properties has been emphasized as a possible key ingredient to in vivo chromatin organization. We use atomic force microscopy (AFM) in air and liquid to image intrinsically straight (synthetic), uncorrelated (hepatitis C RNA virus) and persistent long-range correlated (human) DNA fragments in various ionic conditions such that the molecules freely equilibrate on the mica surface before being captured in a particular conformation. 2D thermodynamic equilibrium is experimentally verified by a detailed statistical analysis of the Gaussian nature of the DNA bend angle fluctuations. We show that the worm-like chain (WLC) model, commonly used to describe the average conformation of long semiflexible polymers, reproduces remarkably well the persistence length estimates for the first two molecules as consistently obtained from (i) mean square end-to-end distance measurement and (ii) mean projection of the end-to-end vector on the initial orientation. Whatever the operating conditions (air or liquid, concentration of metal cations Mg(2+) and/or Ni(2+)), the persistence length found for the uncorrelated viral DNA underestimates the value obtained for the straight DNA. We show that this systematic difference is the signature of the presence of an uncorrelated structural intrinsic disorder in the hepatitis C virus (HCV) DNA fragment that superimposes on local curvatures induced by thermal fluctuations and that only the entropic disorder depends upon experimental conditions. In contrast, the WLC model fails to describe the human DNA conformations. We use a mean-field extension of the WLC model to account for the presence of long-range correlations (LRC) in the intrinsic curvature disorder of human genomic DNA: the stronger the LRC, the smaller the persistence length. The comparison of AFM imaging of human DNA with LRC DNA simulations confirms that the rather small mean square end-to-end distance observed, particularly for G

Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues.

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Alec J Hirsch

2017-03-01

Full Text Available Zika virus (ZIKV, an emerging flavivirus, has recently spread explosively through the Western hemisphere. In addition to symptoms including fever, rash, arthralgia, and conjunctivitis, ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus. We report herein the results of ZIKV infection of adult rhesus macaques. Following subcutaneous infection, animals developed transient plasma viremia and viruria from 1-7 days post infection (dpi that was accompanied by the development of a rash, fever and conjunctivitis. Animals produced a robust adaptive immune response to ZIKV, although systemic cytokine response was minimal. At 7 dpi, virus was detected in peripheral nervous tissue, multiple lymphoid tissues, joints, and the uterus of the necropsied animals. Notably, viral RNA persisted in neuronal, lymphoid and joint/muscle tissues and the male and female reproductive tissues through 28 to 35 dpi. The tropism and persistence of ZIKV in the peripheral nerves and reproductive tract may provide a mechanism of subsequent neuropathogenesis and sexual transmission.

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...

Conditioned taste aversion modifies persistently the subsequent induction of neocortical long-term potentiation in vivo.

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Rodríguez-Durán, Luis F; Castillo, Diana V; Moguel-González, Minerva; Escobar, Martha L

2011-05-01

The ability of neurons to modify their synaptic strength in an activity-dependent manner has a crucial role in learning and memory processes. It has been proposed that homeostatic forms of plasticity might provide the global regulation necessary to maintain synaptic strength and plasticity within a functional dynamic range. Similarly, it is considered that the capacity of synapses to express plastic changes is itself subject to variation dependent on previous experience. In particular, training in several behavioral tasks modifies the possibility to induce long-term potentiation (LTP). Our previous studies in the insular cortex (IC) have shown that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to conditioned taste aversion (CTA) training enhances the retention of this task. The aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, CTA trained rats received high frequency stimulation in the Bla-IC projection in order to induce LTP 48, 72, 96 and 120 h after the aversion test. Our results show that CTA training prevents the subsequent induction of LTP in the Bla-IC projection, for at least 120 h after CTA training. We also showed that pharmacological inhibition of CTA consolidation with anisomycin (1 μl/side; 100 μg/μl) prevents the CTA effect on IC-LTP. These findings reveal that CTA training produces a persistent change in the ability to induce subsequent LTP in the Bla-IC projection in a protein-synthesis dependent manner, suggesting that changes in the ability to induce subsequent synaptic plasticity contribute to the formation and persistence of aversive memories. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

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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.

Long-term course of opioid addiction.

Science.gov (United States)

Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

2015-01-01

Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

Loss of arbuscular mycorrhizal fungal diversity in trap cultures during long-term subculturing.

Science.gov (United States)

Trejo-Aguilar, Dora; Lara-Capistrán, Liliana; Maldonado-Mendoza, Ignacio E; Zulueta-Rodríguez, Ramón; Sangabriel-Conde, Wendy; Mancera-López, María Elena; Negrete-Yankelevich, Simoneta; Barois, Isabelle

2013-12-01

Long-term successional dynamics of an inoculum of arbuscular mycorrhizal fungi (AMF) associated with the maize rhizosphere (from traditionally managed agroecosystems in Los Tuxtlas, Veracruz, Mexico), was followed in Bracchiaria comata trap cultures for almost eight years. The results indicate that AMF diversity is lost following long-term subculturing of a single plant host species. Only the dominant species, Claroideoglomus etunicatum, persisted in pot cultures after 13 cycles. The absence of other morphotypes was demonstrated by an 18S rDNA survey, which confirmed that the sequences present solely belonged to C. etunicatum. Members of Diversisporales were the first to decrease in diversity, and the most persistent species belonged to Glomerales.

Commissioning healthcare for people with long term conditions: the persistence of relational contracting in England's NHS quasi-market.

Science.gov (United States)

Porter, Alison; Mays, Nicholas; Shaw, Sara E; Rosen, Rebecca; Smith, Judith

2013-01-01

challenge the notion of a strict separation of commissioners and providers, and instead demonstrate the adaptive persistence of relational commissioning based on continuity of provision, trust and interdependence between commissioners and providers, at least for services for people with long-term conditions.

PKA and PKC Are Required for Long-Term but Not Short-Term in Vivo Operant Memory in "Aplysia"

Science.gov (United States)

Michel, Maximilian; Green, Charity L.; Lyons, Lisa C.

2011-01-01

We investigated the involvement of PKA and PKC signaling in a negatively reinforced operant learning paradigm in "Aplysia", learning that food is inedible (LFI). In vivo injection of PKA or PKC inhibitors blocked long-term LFI memory formation. Moreover, a persistent phase of PKA activity, although not PKC activity, was necessary for long-term…

Medium- and long-term consequences of pollution on labor supply: evidence from Indonesia

Directory of Open Access Journals (Sweden)

Younoh Kim

2017-04-01

Full Text Available Abstract We use a natural experiment in Indonesia to study the medium- and long-term effects of air pollution on labor supply. We find that exposure to air pollution reduces hours worked and while the medium-term effects are larger in magnitude, some effects do persist in the long term. More interestingly, we are able to provide some insight regarding the underlying channels that contribute to the reduced labor supply. Own health seems to be the only responsible channel in the long term, while in the medium term, a different channel based on dependent caregiving is the most important. JEL Classification: J22, Q53

Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory.

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Santini, Emanuela; Huynh, Thu N; Klann, Eric

2014-01-01

The complexity of memory formation and its persistence is a phenomenon that has been studied intensely for centuries. Memory exists in many forms and is stored in various brain regions. Generally speaking, memories are reorganized into broadly distributed cortical networks over time through systems level consolidation. At the cellular level, storage of information is believed to initially occur via altered synaptic strength by processes such as long-term potentiation. New protein synthesis is required for long-lasting synaptic plasticity as well as for the formation of long-term memory. The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of cap-dependent protein synthesis and is required for numerous forms of long-lasting synaptic plasticity and long-term memory. As such, the study of mTORC1 and protein factors that control translation initiation and elongation has enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we discuss the molecular mechanisms that regulate protein synthesis as well as pharmacological and genetic manipulations that demonstrate the requirement for proper translational control in long-lasting synaptic plasticity and long-term memory formation. © 2014 Elsevier Inc. All rights reserved.

Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients.

Science.gov (United States)

Diaz, Alba; Alós, Llúcia; León, Agathe; Mozos, Anna; Caballero, Miguel; Martinez, Antonio; Plana, Montserrat; Gallart, Teresa; Gil, Cristina; Leal, Manuel; Gatell, Jose M; García, Felipe

2010-08-24

The factors associated with fibrosis in lymphoid tissue in long-term treated HIV-infected patients and their correlation with immune reconstitution were assessed. Tonsillar biopsies were performed in seven antiretroviral-naive patients and 29 successfully treated patients (median time on treatment, 61 months). Twenty patients received protease inhibitors-sparing regimens and nine protease inhibitor-containing regimens. Five tonsillar resections of HIV-negative individuals were used as controls. Lymphoid tissue architecture, collagen deposition (fibrosis) and the mean interfollicular CD4(+) cell count per mum were assessed. Naive and long-term treated HIV-infected patients had a higher proportion of fibrosis than did HIV-uninfected persons (P lymphoid tissue (P = 0.03) and smaller increase in peripheral CD4(+) T cells (r = -0.40, P = 0.05). The factors independently associated with fibrosis in lymphoid tissue were age (P lymphoid tissue viral load when compared with patients with undetectable lymphoid tissue viral load (median 5 vs. 12%, respectively, P = 0.017) and patients receiving a protease inhibitor-sparing vs. a protease inhibitor-containing regimen (median 8 vs. 2.5%, respectively, P = 0.04). Fibrosis in lymphoid tissue was associated with a poor reconstitution of CD4(+) T cells and long-term antiretroviral therapy did not reverse this abnormality. HIV infection, older age, a detectable level of lymphoid tissue viral load in treated patients and protease inhibitor-sparing regimens seem to favour fibrosis in lymphoid tissue.

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

Host factors influencing viral persistence

DEFF Research Database (Denmark)

Thomsen, Allan Randrup; Nansen, A; Ørding Andreasen, Susanne

2000-01-01

host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand...... replication, mice lacking the ability to produce interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates...

Implicit short- and long-term memory direct our gaze in visual search.

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Kruijne, Wouter; Meeter, Martijn

2016-04-01

Visual attention is strongly affected by the past: both by recent experience and by long-term regularities in the environment that are encoded in and retrieved from memory. In visual search, intertrial repetition of targets causes speeded response times (short-term priming). Similarly, targets that are presented more often than others may facilitate search, even long after it is no longer present (long-term priming). In this study, we investigate whether such short-term priming and long-term priming depend on dissociable mechanisms. By recording eye movements while participants searched for one of two conjunction targets, we explored at what stages of visual search different forms of priming manifest. We found both long- and short- term priming effects. Long-term priming persisted long after the bias was present, and was again found even in participants who were unaware of a color bias. Short- and long-term priming affected the same stage of the task; both biased eye movements towards targets with the primed color, already starting with the first eye movement. Neither form of priming affected the response phase of a trial, but response repetition did. The results strongly suggest that both long- and short-term memory can implicitly modulate feedforward visual processing.

Testing Hypotheses in an I(2) Model with Applications to the Persistent Long Swings in the Dmk/$ Rate

DEFF Research Database (Denmark)

Johansen, Søren; Juselius, Katarina; Frydman, Roman

and persistent swings in the foreign exchange market between Germany and USA. The data analyzed consist of nominal exchange rates, relative prices, US inflation rate, two long-term interest rates and two short-term interest rates over the 1975-1999 period. One important aim of the paper is to demonstrate...... that by structuring the data with the help of the I(2) model one can achieve a better understanding of the empirical regularities underlying the persistent swings in nominal exchange rates, typical in periods of floating exchange rates...

Persistent Associative Plasticity at an Identified Synapse Underlying Classical Conditioning Becomes Labile with Short-Term Homosynaptic Activation.

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Hu, Jiangyuan; Schacher, Samuel

2015-12-09

Synapses express different forms of plasticity that contribute to different forms of memory, and both memory and plasticity can become labile after reactivation. We previously reported that a persistent form of nonassociative long-term facilitation (PNA-LTF) of the sensorimotor synapses in Aplysia californica, a cellular analog of long-term sensitization, became labile with short-term heterosynaptic reactivation and reversed when the reactivation was followed by incubation with the protein synthesis inhibitor rapamycin. Here we examined the reciprocal impact of different forms of short-term plasticity (reactivations) on a persistent form of associative long-term facilitation (PA-LTF), a cellular analog of classical conditioning, which was expressed at Aplysia sensorimotor synapses when a tetanic stimulation of the sensory neurons was paired with a brief application of serotonin on 2 consecutive days. The expression of short-term homosynaptic plasticity [post-tetanic potentiation or homosynaptic depression (HSD)], or short-term heterosynaptic plasticity [serotonin-induced facilitation or neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa)-induced depression], at synapses expressing PA-LTF did not affect the maintenance of PA-LTF. The kinetics of HSD was attenuated at synapses expressing PA-LTF, which required activation of protein kinase C (PKC). Both PA-LTF and the attenuated kinetics of HSD were reversed by either a transient blockade of PKC activity or a homosynaptic, but not heterosynaptic, reactivation when paired with rapamycin. These results indicate that two different forms of persistent synaptic plasticity, PA-LTF and PNA-LTF, expressed at the same synapse become labile when reactivated by different stimuli. Activity-dependent changes in neural circuits mediate long-term memories. Some forms of long-term memories become labile and can be reversed with specific types of reactivations, but the mechanism is complex. At the cellular level, reactivations that induce a

Frequency and Cause of Persistent Symptoms in Celiac Disease Patients on a Long-term Gluten-free Diet.

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Stasi, Elisa; Marafini, Irene; Caruso, Roberta; Soderino, Federica; Angelucci, Erika; Del Vecchio Blanco, Giovanna; Paoluzi, Omero A; Calabrese, Emma; Sedda, Silvia; Zorzi, Francesca; Pallone, Francesco; Monteleone, Giovanni

2016-03-01

To estimate the frequency and cause of nonresponsive celiac disease (CD). Treatment of CD is based on life-long adherence to a gluten-free diet (GFD). Some celiac patients experience persistence of symptoms despite a GFD. This condition is defined as nonresponsive CD. Celiac patients on a GFD for at least 12 months underwent diet compliance assessment, laboratory tests, breath tests, endoscopic, and histologic evaluations according to the symptoms/signs reported. Seventy of 321 (21.8%) patients had persistent or recurrent symptoms/signs. The cause of symptom persistence was evaluated in 56 of 70 patients. Thirteen of 56 (23%) patients were antiendomysial antibody positive. Among the patients with negative serology, 1 had fibromyalgia, and 3 had evidence that disproved the diagnosis of CD. The remaining 39 patients with negative serology underwent duodenal biopsy sampling, which evidenced histologic alterations in 24 patients. Among the 15 patients with normal histology 3 were lactose intolerant, 9 had irritable bowel syndrome, 2 had gastroesophageal reflux disease, and in 1 patient a cause for the persistent symptom was not identified. In patients with confirmed diagnosis of CD, exposure to dietary gluten was the main cause of persistence of symptoms/signs, and consistently after dietary modification, symptoms resolved in 63% of the patients at later time points during follow-up. Nonresponsive CD occurs in nearly one fifth of celiac patients on GFD and its occurrence suggests further investigations to optimize the management of celiac patients.

CT images of infantile viral encephalitis

International Nuclear Information System (INIS)

Sugimoto, Tateo; Okazaki, Hitoshi; Woo, Man

1985-01-01

Cranial CT scanning was undertaken in 40 patients with infantile viral encephalitis seen from 1977 to 1983. According to the pathogenic viruses, abnormal CT findings were detected most frequently in cases of herpes simplex encephalitis (HSE), followed by non-eruptive viral encephalitis, measles encephalitis, and rubella encephalitis in that order, which coincided well with neurological prognosis. Although CT findings lay within a normal range in cases of measles encephalitis, except a case in which cerebral ventricle was slightly dilated, the degree of consciousness disturbance was unfavorable and it persisted long. This revealed that there is no distinct correlation between the degree of consciousness disturbance and CT findings. Normal CT findings were detected in 13% of patients aged less than 5 years and 76.5% of patients aged 5 years or more. In many patients who had an attack of viral encephalitis at the age of 5 years or more, epileptic seizures occurred frequently, even though CT findings were normal. (Namekawa, K.)

Biochemical Mechanisms and Energy Strategies of Geobacter sulfurreducens for Long- Term Survival

Science.gov (United States)

Helmus, R. A.; Liermann, L. J.; Brantley, S. L.; Tien, M.

2008-12-01

Numerous species of bacteria have been observed to exhibit a growth advantage in stationary phase (GASP) phenotype, indicating that microorganisms starved of an energy source may adapt to allow for long-term survival. Understanding how Geobacter sulfurreducens persists using various metal forms as energy sources and whether a GASP phenotype develops during long-term growth are important for efficient application of this bacterium to sites requiring engineered bioremediation of soluble metals. Thus, we investigated the growth kinetics and survival of G. sulfurreducens. The growth rate of G. sulfurreducens was highest when cultured with soluble iron and generally higher on iron oxide than manganese oxide, suggesting that soluble metal forms are more readily utilized as energy sources by G. sulfurreducens. By monitoring the abundance of G. sulfurreducens in batch cultures for >6 months, distinct growth, stationary, and prolonged starvation phases were observed and a cell density of 105- 106 cells/mL persisted under long-term starvation conditions. The outgrowth of an aged G. sulfurreducens strain co-cultured with a young strain was monitored as a measure of the existence of the GASP phenotype. As the strains aged, the rpoS gene was cloned and sequenced at different stages of growth to identify mutations corresponding to a growth advantage. The results of these studies provide insight into the use of various metal forms for growth by G. sulfurreducens and its ability to persist when starved of energy sources.

Different Immunological Phenotypes Associated with Preserved CD4+ T Cell Counts in HIV-Infected Controllers and Viremic Long Term Non-Progressors

DEFF Research Database (Denmark)

Gaardbo, Julie Christine; Hartling, Hans J; Ronit, Andreas

2013-01-01

HIV-infected controllers control viral replication and maintain normal CD4+ T cell counts. Long Term Non-Progressors (LTNP) also maintain normal CD4+ T cell counts, but have on-going viral replication. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell...

Distinct cerebellar engrams in short-term and long-term motor learning.

Science.gov (United States)

Wang, Wen; Nakadate, Kazuhiko; Masugi-Tokita, Miwako; Shutoh, Fumihiro; Aziz, Wajeeha; Tarusawa, Etsuko; Lorincz, Andrea; Molnár, Elek; Kesaf, Sebnem; Li, Yun-Qing; Fukazawa, Yugo; Nagao, Soichi; Shigemoto, Ryuichi

2014-01-07

Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-term adaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation.

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains.

Science.gov (United States)

Sudhakaran, Indulekha P; Ramaswami, Mani

2017-05-04

Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs

Long term persistence in the sea surface temperature fluctuations

OpenAIRE

Monetti, Roberto A.; Havlin, Shlomo; Bunde, Armin

2002-01-01

We study the temporal correlations in the sea surface temperature (SST) fluctuations around the seasonal mean values in the Atlantic and Pacific oceans. We apply a method that systematically overcome possible trends in the data. We find that the SST persistence, characterized by the correlation $C(s)$ of temperature fluctuations separated by a time period $s$, displays two different regimes. In the short-time regime which extends up to roughly 10 months, the temperature fluctuations display a...

Genetic Variability of Bovine Viral Diarrhea Virus and Evidence for a Possible Genetic Bottleneck during Vertical Transmission in Persistently Infected Cattle.

Directory of Open Access Journals (Sweden)

Natalie Dow

Full Text Available Bovine viral diarrhea virus (BVDV, a Pestivirus in the family Flaviviridae, is an economically important pathogen of cattle worldwide. The primary propagators of the virus are immunotolerant persistently infected (PI cattle, which shed large quantities of virus throughout life. Despite the absence of an acquired immunity against BVDV in these PI cattle there are strong indications of viral variability that are of clinical and epidemiological importance. In this study the variability of E2 and NS5B sequences in multiple body compartments of PI cattle were characterized using clonal sequencing. Phylogenetic analyses revealed that BVDV exists as a quasispecies within PI cattle. Viral variants were clustered by tissue compartment significantly more often than expected by chance alone with the central nervous system appearing to be a particularly important viral reservoir. We also found strong indications for a genetic bottleneck during vertical transmission from PI animals to their offspring. These quasispecies analyses within PI cattle exemplify the role of the PI host in viral propagation and highlight the complex dynamics of BVDV pathogenesis, transmission and evolution.

5-Bromo-2'-deoxyuridine impairs long-term food aversion memory in edible snail.

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Efimova, O I; Anokhin, K V

2012-09-01

We studied the involvement of DNA synthesis into molecular mechanisms of long-term memory. Nucleoside analogue 5-bromo-2'-deoxyuridine (BrdU) is known to incorporate into synthesizing DNA and prevent subsequent DNA replication from this region. To investigate the effect of BrdU administration on long-term memory, terrestrial gastropods edible snails Helix lucorum were trained in the food aversion paradigm. Single-session training (carrot presentation combined with application of 10% quinine solution, three carrot presentations with 10-min intervals) resulted in the formation of long-term memory that persisted for at least 45° days. BrdU administration (250 mg/kg) 30 min before training impaired long-term memory tested 24 h later. Immunohistochemical study revealed BrdU incorporation in the nuclei of identified neurons of defensive behavior.

Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

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Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

2015-01-01

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.

Science.gov (United States)

Lyons, Lisa C; Gardner, Jacob S; Lentsch, Cassidy T; Gandour, Catherine E; Krishnan, Harini C; Noakes, Eric J

2017-01-01

In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

Directory of Open Access Journals (Sweden)

Peter Serrano

2008-12-01

Full Text Available How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta, an autonomously active atypical protein kinase C (PKC isoform critical for the maintenance of long-term potentiation (LTP. PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH and basolateral amygdala (BLA on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise

PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

Science.gov (United States)

Serrano, Peter; Friedman, Eugenia L; Kenney, Jana; Taubenfeld, Stephen M; Zimmerman, Joshua M; Hanna, John; Alberini, Cristina; Kelley, Ann E; Maren, Stephen; Rudy, Jerry W; Yin, Jerry C P; Sacktor, Todd C; Fenton, André A

2008-12-23

How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta), an autonomously active atypical protein kinase C (PKC) isoform critical for the maintenance of long-term potentiation (LTP). PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP) by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH) and basolateral amygdala (BLA) on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US) associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise, or

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

Science.gov (United States)

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

2008-05-12

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

Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus.

Science.gov (United States)

Medeiros, Sheila de Oliveira; Abreu, Celina Monteiro; Delvecchio, Rodrigo; Ribeiro, Anísia Praxedes; Vasconcelos, Zilton; Brindeiro, Rodrigo de Moraes; Tanuri, Amilcar

2016-04-01

Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years. Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group. CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment. The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo. © ISFM and AAFP 2015.

Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein.

Directory of Open Access Journals (Sweden)

Karishma T Mody

Full Text Available Bovine Viral Diarrhoea Virus (BVDV is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2 antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm3 g(-1 have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 μg/SV-140 (500 μg and FD oE2 (100 μg/SV-140 (500 μg to induce long-term immunity was compared to immunisation with oE2 (100 μg together with the conventional adjuvant Quil-A from the Quillaja saponira (10 μg in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 μg SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications.

Long-term exposure to noise impairs cortical sound processing and attention control.

Science.gov (United States)

Kujala, Teija; Shtyrov, Yury; Winkler, Istvan; Saher, Marieke; Tervaniemi, Mari; Sallinen, Mikael; Teder-Sälejärvi, Wolfgang; Alho, Kimmo; Reinikainen, Kalevi; Näätänen, Risto

2004-11-01

Long-term exposure to noise impairs human health, causing pathological changes in the inner ear as well as other anatomical and physiological deficits. Numerous individuals are daily exposed to excessive noise. However, there is a lack of systematic research on the effects of noise on cortical function. Here we report data showing that long-term exposure to noise has a persistent effect on central auditory processing and leads to concurrent behavioral deficits. We found that speech-sound discrimination was impaired in noise-exposed individuals, as indicated by behavioral responses and the mismatch negativity brain response. Furthermore, irrelevant sounds increased the distractibility of the noise-exposed subjects, which was shown by increased interference in task performance and aberrant brain responses. These results demonstrate that long-term exposure to noise has long-lasting detrimental effects on central auditory processing and attention control.

Persistent organic pollutants (POPs) in the atmosphere of coastal areas of the Ross Sea, Antarctica: Indications for long-term downward trends.

Science.gov (United States)

Pozo, Karla; Martellini, Tania; Corsolini, Simonetta; Harner, Tom; Estellano, Victor; Kukučka, Petr; Mulder, Marie D; Lammel, Gerhard; Cincinelli, Alessandra

2017-07-01

Passive air samplers were used to evaluate long-term trends and spatial distribution of trace organic compounds in Antarctica. Duplicate PUF disk samplers were deployed at six automatic weather stations in the coastal area of the Ross sea (East Antarctica), between December 2010 and January 2011, during the XXVI Italian Scientific Research Expedition. Among the investigated persistent organic compounds, Hexachlorobenzene was the most abundant, with air concentrations ranging from 0.8 to 50 pg m -3 . In general, the following decreasing concentration order was found for the air samples analyzed: HCB > PeCB > PCBs > DDTs > HCHs. While HCB concentrations were in the same range as those reported in the atmosphere of other Antarctic sampling areas and did not show a decline, HCHs and DDTs levels were lower or similar to those determined one or two decades ago. In general, the very low concentrations reflected the pristine state of the East Antarctica air. Backward trajectories indicated the prevalence of air masses coming from the Antarctic continent. Local contamination and volatilization from ice were suggested as potential sources for the presence of persistent organic pollutants in the atmosphere. Copyright © 2017 Elsevier Ltd. All rights reserved.

Viral Small-RNA Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection.

Science.gov (United States)

Zografidis, Aris; Van Nieuwerburgh, Filip; Kolliopoulou, Anna; Apostolou-Karampelis, Konstantinos; Head, Steven R; Deforce, Dieter; Smagghe, Guy; Swevers, Luc

2015-11-01

The lepidopteran innate immune response against RNA viruses remains poorly understood, while in other insects several studies have highlighted an essential role for the exo-RNAi pathway in combating viral infection. Here, by using deep-sequencing technology for viral small-RNA (vsRNA) assessment, we provide evidence that exo-RNAi is operative in the silkworm Bombyx mori against both persistent and pathogenic infection of B. mori cytoplasmic polyhedrosis virus (BmCPV) which is characterized by a segmented double-stranded RNA (dsRNA) genome. Further, we show that Dicer-2 predominantly targets viral dsRNA and produces 20-nucleotide (nt) vsRNAs, whereas an additional pathway is responsive to viral mRNA derived from segment 10. Importantly, vsRNA distributions, which define specific hot and cold spot profiles for each viral segment, to a considerable degree overlap between Dicer-2-related (19 to 21 nt) and Dicer-2-unrelated vsRNAs, suggesting a common origin for these profiles. We found a degenerate motif significantly enriched at the cut sites of vsRNAs of various lengths which link an unknown RNase to the origins of vsRNAs biogenesis and distribution. Accordingly, the indicated RNase activity may be an important early factor for the host's antiviral defense in Lepidoptera. This work contributes to the elucidation of the lepidopteran antiviral response against infection of segmented double-stranded RNA (dsRNA) virus (CPV; Reoviridae) and highlights the importance of viral small-RNA (vsRNA) analysis for getting insights into host-pathogen interactions. Three vsRNA pathways are implicated in antiviral defense. For dsRNA, two pathways are proposed, either based on Dicer-2 cleavage to generate 20-nucleotide vsRNAs or based on the activity of an uncharacterized endo-RNase that cleaves the viral RNA substrate at a degenerate motif. The analysis also indicates the existence of a degradation pathway that targets the positive strand of segment 10. Copyright © 2015, American

BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.

Science.gov (United States)

Yoo, Miran; Choi, Kwang-Yeon; Kim, Jieun; Kim, Mujun; Shim, Jaehoon; Choi, Jun-Hyeok; Cho, Hye-Yeon; Oh, Jung-Pyo; Kim, Hyung-Su; Kaang, Bong-Kiun; Han, Jin-Hee

2017-03-29

Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage. To address these questions, we used viral vector approaches to either decrease or increase BAF53b function specifically in the lateral amygdala of adult mice in auditory fear conditioning paradigm. Knockdown of Baf53b before training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory formation, which was accompanied by increase in thin-type spine density. Together, our results provide the evidence that BAF53b is induced after learning, and show that such increase of BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity. SIGNIFICANCE STATEMENT Recent works in the rodent brain begin to link nucleosome remodeling-dependent epigenetic mechanism to memory consolidation. Here we show that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons at the late phase of consolidation after fear conditioning. Using specific gene knockdown or overexpression approaches, we identify the critical role of BAF53b in the lateral amygdala neurons for

Identification of alpha interferon-induced envelope mutations of hepatitis C virus in vitro associated with increased viral fitness and interferon resistance

DEFF Research Database (Denmark)

Serre, Stéphanie B N; Krarup, Henrik B; Bukh, Jens

2013-01-01

Alpha interferon (IFN-α) is an essential component of innate antiviral immunity and of treatment regimens for chronic hepatitis C virus (HCV) infection. Resistance to IFN might be important for HCV persistence and failure of IFN-based therapies. Evidence for HCV genetic correlates of IFN resistance...... is limited. Experimental studies were hampered by lack of HCV culture systems. Using genotype (strain) 1a(H77) and 3a(S52) Core-NS2 JFH1-based recombinants, we aimed at identifying viral correlates of IFN-α resistance in vitro. Long-term culture with IFN-α2b in Huh7.5 cells resulted in viral spread...... with acquisition of putative escape mutations in HCV structural and nonstructural proteins. Reverse genetic studies showed that primarily amino acid changes I348T in 1a(H77) E1 and F345V/V414A in 3a(S52) E1/E2 increased viral fitness. Single-cycle assays revealed that I348T and F345V/V414A enhanced viral entry...

Experimental Inoculation in Rats and Mice by the Giant Marseillevirus Leads to Long-Term Detection of Virus

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Sarah Aherfi

2018-03-01

Full Text Available The presence of the giant virus of amoeba Marseillevirus has been identified at many different sites on the human body, including in the bloodstream of asymptomatic subjects, in the lymph nodes of a child with adenitis, in one adult with Hodgkin's disease, and in the pharynx of an adult. A high seroprevalence of the Marseillevirus has been recorded in the general population. Whether Marseillevirus can disseminate and persist within a mammal after entry remains unproven. We aimed to assess the ability of the virus to disseminate and persist into healthy organisms, especially in the lymphoid organs. Parenteral inoculations were performed by intraperitoneal injection (in rats and mice or intravenous injection (in rats. Airway inoculation was performed by aerosolization (in mice. Dissemination and persistence were assessed by using PCR and amebal co-culture. Serologies were performed by immunofluorescent assay. Pathological examination was conducted after standard and immunohistochemistry staining. After intraperitoneal inoculation in mice and rats, Marseillevirus was detected in the bloodstream during the first 24 h. Persistence was noted until the end of the experiment, i.e., at 14 days in rats. After intravenous inoculation in rats, the virus was first detected in the blood until 48 h and then in deep organs with infectious virus detected until 14 and 21 days in the liver and the spleen, respectively. Its DNA was detected for up to 30 days in the liver and the spleen. After aerosolization in mice, infectious Marseillevirus was present in the lungs and nasal associated lymphoid tissue until 30 days post inoculation but less frequently and at a lower viral load in the lung than in the nasal associated lymphoid tissue. No other site of dissemination was found after aerosol exposure. Despite no evidence of disease being observed, the 30-day long persistence of Marseillevirus in rats and mice, regardless of the route of inoculation, supports the

Persistent short-term memory defects following sleep deprivation in a drosophila model of Parkinson disease.

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Seugnet, Laurent; Galvin, James E; Suzuki, Yasuko; Gottschalk, Laura; Shaw, Paul J

2009-08-01

Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on shortterm memory using a Drosophila model of Parkinson disease. Transgenic strains of Drosophila melanogaster. Using the GAL4-UAS system, human alpha-synuclein was expressed throughout the nervous system of adult flies. Alpha-synuclein expressing flies (alpha S flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry. MEASURMENTS AND RESULTS: When sleep deprived at an intermediate stage of the pathology, alpha S flies showed persistent short-term memory deficits that lasted > or = 3 days. Cognitive deficits were not observed in younger alpha S flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived alpha S flies. Blocking D1-like receptors during sleep deprivation prevented persistent shortterm memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits. These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics.

HoBi-like virus challenge of pregnant cows that had previously given birth to calves persistently infected with bovine viral diarrhea virus

Science.gov (United States)

The ability of bovine viral diarrhea viruses (BVDV) to establish persistent infection (PI) following fetal infection is central to keeping these viruses circulating. Similarly, an emerging species of pestivirus, HoBi-like viruses, is also able to establish PIs. Dams that are not PI, but carrying PI ...

Presynaptic learning and memory with a persistent firing neuron and a habituating synapse: a model of short term persistent habituation.

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Ramanathan, Kiruthika; Ning, Ning; Dhanasekar, Dhiviya; Li, Guoqi; Shi, Luping; Vadakkepat, Prahlad

2012-08-01

Our paper explores the interaction of persistent firing axonal and presynaptic processes in the generation of short term memory for habituation. We first propose a model of a sensory neuron whose axon is able to switch between passive conduction and persistent firing states, thereby triggering short term retention to the stimulus. Then we propose a model of a habituating synapse and explore all nine of the behavioral characteristics of short term habituation in a two neuron circuit. We couple the persistent firing neuron to the habituation synapse and investigate the behavior of short term retention of habituating response. Simulations show that, depending on the amount of synaptic resources, persistent firing either results in continued habituation or maintains the response, both leading to longer recovery times. The effectiveness of the model as an element in a bio-inspired memory system is discussed.

Long-term use of neonatal helmet-CPAP: a case report.

Science.gov (United States)

Doglioni, N; Micaglio, M; Zanardo, V; Trevisanuto, D

2009-12-01

In a recent short-term physiological study, we demonstrated a new continuous positive airway pressure (CPAP) system (neonatal helmet-CPAP) that could be a feasible device for managing preterm infants needing continuous distending pressure with better tolerability than nasal-CPAP. However, its application for a long-term period has never been reported in neonates. Here, we describe the use of neonatal helmet-CPAP in a neonate with persistent pulmonary hypertension of the newborn. Twenty minutes after neonatal helmet-CPAP placement, the baseline post-ductal tcSaO2 (66%) and alveolar-arterial gradient O2 improved from 66% and 648 mmHg to 100% and 465 mmHg, respectively. The neonatal helmet-CPAP was applied for 48 hours and was well-tolerated by the patient without complications. Long-term use of neonatal helmet-CPAP appears feasible and well-tolerated. Comparative trials are needed.

Long-term persistence, density dependence and effects of climate change on rosyside dace (Cyprinidae)

Science.gov (United States)

Gary D. Grossman; Gary Sundin; Robert E. Ratajczak

2016-01-01

SummaryWe used long-term population data for rosyside dace (Clinostomus funduloides), a numerically dominant member of a stochastically organised fish assemblage, to evaluate the relative importance of density-dependent and density-independent processes to population...

Indoor air in long term care facilities and spread of infectious diseases

NARCIS (Netherlands)

te Kulve, M.; Loomans, M.G.L.C.; Huisman, E.; Kort, H.S.M.

2014-01-01

Not much is known about the favourable indoor air conditions in long term care facilities (ltcf’s), where older adults suffering from dementia live. Due to the decrease in cognition function, it is hard to evaluate comfort and health in this group. Nevertheless, infectious diseases are a persistent

Antimicrobial stewardship in long term care facilities: what is effective?

OpenAIRE

Nicolle, Lindsay E

2014-01-01

Intense antimicrobial use in long term care facilities promotes the emergence and persistence of antimicrobial resistant organisms and leads to adverse effects such as C. difficile colitis. Guidelines recommend development of antimicrobial stewardship programs for these facilities to promote optimal antimicrobial use. However, the effectiveness of these programs or the contribution of any specific program component is not known. For this review, publications describing evaluation of antimicro...

Long-Term Neurodevelopmental Outcome after Doxapram for Apnea of Prematurity.

Science.gov (United States)

Ten Hove, Christine H; Vliegenthart, Roseanne J; Te Pas, Arjan B; Brouwer, Emma; Rijken, Monique; van Wassenaer-Leemhuis, Aleid G; van Kaam, Anton H; Onland, Wes

2016-01-01

Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP). To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established. From a retrospective cohort of preterm infants with a gestational age (GA) large, well-designed, placebo-controlled randomized trial. © 2016 The Author(s) Published by S. Karger AG, Basel.

International Long-term Data and Analysis Preservation

CERN Document Server

Shiers, J; Rahal, G; South, D; Guelzow, V; CERN. Geneva. IT Department

2011-01-01

The preservation of scientific data for long-term use and re-analysis has been identified as a key requirement in the field of High Energy Physics and other disciplines such as Astronomy and Astrophysics, as well as Life and Earth Sciences. In collaboration with related projects in the US (in particular in close collaboration with the National Science Foundation and Department of Energy) the proposed project would take the work of the Data Preservation in HEP Study group that defines the physics motivation for long-term data preservation and many of the associated issues, and extend this to cover not only the existing use cases but also consider the needs of the LHC experiments at CERN. This work would ensure the persistent availability of existing data and enable it to be shared between organisations and across national boundaries. Now is the time to define standards for data and meta-data formats and address access and authorization issues for on-going experiments (e.g. those at the LHC) – issues that hav...

Issues for the long term management of radioactive waste

International Nuclear Information System (INIS)

Schneider, T.; Schieber, C.; Lavelle, S.

2006-01-01

High-level radioactive waste are currently managed in interim storage installations, providing an adequate protection of the public and the workers for the short term period. However, the long-term persistence of the radioactivity of the waste gives a new timescale dimension, never experimented by the society for the development of protection systems. In the framework of the European Commission research project 'COWAM-2' (COmmunity WAste Management) dedicated to the governance of radioactive waste management, the issues of 'long term governance' have been addressed by exploring the elements which can contribute to a better integration of the technical and societal time dimensions, taking into account technical, ethical, economic and organizational considerations. The originality of this project is to address the various issues within working groups involving stakeholders from different origins and European countries together with a research team. After a discussion on the time dimensions to be taken into account from the technical and societal perspective, this paper presents, mainly based on the findings of the COWAM-2 project, a brief analysis of the ethical criteria to be considered when future generations are concerned as well as some performance criteria regarding long term governance. Finally, it proposes a discussion on the interest for the radiation protection experts to engage a process with stakeholders concerned by radioactive waste management in order to favour the emergence of a sustainable management responding to the issues at stake and including radiation protection considerations for long term periods. (authors)

Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats

Science.gov (United States)

2013-01-01

Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable. PMID:23675947

Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats.

Science.gov (United States)

Bachofen, Claudia; Vogt, Hans-Rudolf; Stalder, Hanspeter; Mathys, Tanja; Zanoni, Reto; Hilbe, Monika; Schweizer, Matthias; Peterhans, Ernst

2013-05-15

Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable.

Long-term Study of a Quadrivalent Human Papillomavirus Vaccine

DEFF Research Database (Denmark)

Ferris, Daron; Samakoses, Rudiwilai; Block, Stan L

2014-01-01

BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6...... objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease. RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti-HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none developed HPV6....../11/16/18-related disease or persistent infection of ≥12 months' duration. Acquisition of new sexual partners (among those ≥16 years) was ∼1 per year. Subjects receiving HPV4 vaccine at month 30 (mean age 15 years) had a similar baseline rate of seropositivity to ≥1 of the 4 HPV types to those vaccinated at day 1...

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

DEFF Research Database (Denmark)

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

2015-01-01

with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8-year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0-25.6%). The corresponding risks for HPV18......In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During...... 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women...

Distinguishing patterns in the dynamics of long-term medication use by Markov analysis: beyond persistence

Directory of Open Access Journals (Sweden)

Lammers Jan-Willem J

2007-07-01

Full Text Available Abstract Background In order to accurately distinguish gaps of varying length in drug treatment for chronic conditions from discontinuation without resuming therapy, short-term observation does not suffice. Thus, the use of inhalation corticosteroids (ICS in the long-term, during a ten-year period is investigated. To describe medication use as a continuum, taking into account the timeliness and consistency of refilling, a Markov model is proposed. Methods Patients, that filled at least one prescription in 1993, were selected from the PHARMO medical record linkage system (RLS containing >95% prescription dispensings per patient originating from community pharmacy records of 6 medium-sized cities in the Netherlands. The probabilities of continuous use, the refilling of at least one ICS prescription in each year of follow-up, and medication free periods were assessed by Markov analysis. Stratified analysis according to new use was performed. Results The transition probabilities of the refilling of at least one ICS prescription in the subsequent year of follow-up, were assessed for each year of follow-up and for the total study period. The change of transition probabilities in time was evaluated, e.g. the probability of continuing ICS use of starters in the first two years (51% of follow-up increased to more than 70% in the following years. The probabilities of different patterns of medication use were assessed: continuous use (7.7%, cumulative medication gaps (1–8 years 69.1% and discontinuing (23.2% during ten-year follow-up for new users. New users had lower probability of continuous use (7.7% and more variability in ICS refill patterns than previous users (56%. Conclusion In addition to well-established methods in epidemiology to ascertain compliance and persistence, a Markov model could be useful to further specify the variety of possible patterns of medication use within the continuum of adherence. This Markov model describes variation in

Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans.

Science.gov (United States)

Vita-More, Natasha; Barranco, Daniel

2015-10-01

Can memory be retained after cryopreservation? Our research has attempted to answer this long-standing question by using the nematode worm Caenorhabditis elegans, a well-known model organism for biological research that has generated revolutionary findings but has not been tested for memory retention after cryopreservation. Our study's goal was to test C. elegans' memory recall after vitrification and reviving. Using a method of sensory imprinting in the young C. elegans, we establish that learning acquired through olfactory cues shapes the animal's behavior and the learning is retained at the adult stage after vitrification. Our research method included olfactory imprinting with the chemical benzaldehyde (C6H5CHO) for phase-sense olfactory imprinting at the L1 stage, the fast-cooling SafeSpeed method for vitrification at the L2 stage, reviving, and a chemotaxis assay for testing memory retention of learning at the adult stage. Our results in testing memory retention after cryopreservation show that the mechanisms that regulate the odorant imprinting (a form of long-term memory) in C. elegans have not been modified by the process of vitrification or by slow freezing.

Fundamental bound on the persistence and capacity of short-term memory stored as graded persistent activity.

Science.gov (United States)

Koyluoglu, Onur Ozan; Pertzov, Yoni; Manohar, Sanjay; Husain, Masud; Fiete, Ila R

2017-09-07

It is widely believed that persistent neural activity underlies short-term memory. Yet, as we show, the degradation of information stored directly in such networks behaves differently from human short-term memory performance. We build a more general framework where memory is viewed as a problem of passing information through noisy channels whose degradation characteristics resemble those of persistent activity networks. If the brain first encoded the information appropriately before passing the information into such networks, the information can be stored substantially more faithfully. Within this framework, we derive a fundamental lower-bound on recall precision, which declines with storage duration and number of stored items. We show that human performance, though inconsistent with models involving direct (uncoded) storage in persistent activity networks, can be well-fit by the theoretical bound. This finding is consistent with the view that if the brain stores information in patterns of persistent activity, it might use codes that minimize the effects of noise, motivating the search for such codes in the brain.

Surviving in Changing Seascapes: Sediment Dynamics as Bottleneck for Long-Term Seagrass Presence

NARCIS (Netherlands)

Suykerbuyk, W.; Bouma, T.J.; Govers, L.L.; Giesen, K.; de Jong, D.J.; Herman, P.M.J.; Hendriks, J.; van Katwijk, M.M.

2016-01-01

Changes in the seascape often result in altered hydrodynamics that lead to coinciding changes in sediment dynamics. Little is known on how altered sediment dynamics affect long-term seagrass persistence. We studied the thresholds of sediment dynamics in relation to seagrass presence by comparing

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

Directory of Open Access Journals (Sweden)

Kesic Matthew

2008-05-01

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

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

Long-term outcomes of unilateral transtibial amputations.

Science.gov (United States)

Ebrahimzadeh, Mohamad H; Hariri, Sanaz

2009-06-01

the long-term outcomes of wartime transtibial amputations have not been well documented. The purpose of this case series is to present the long-term functional, social, and psychological outcomes of modern-day military unilateral transtibial amputees. the Iranian Veterans Administration of the Khorasan province invited their Iranian military amputees from the Iran-Iraq War (1980-1988) to its medical center for evaluation. The patients filled out a detailed questionnaire and were interviewed and examined by each team member. two hundred (77%) of the 260 invited amputees were willing and able to come back for follow-up. Ninety-six of these patients (48%) were unilateral transtibial amputation. The average follow-up was 17.4 years (range 15-22 years). Land mines were the leading cause of war injury necessitating a transtibial amputation (68%). The most common symptoms about their amputated limbs were phantom sensations (54%), phantom pain (17%), and stump pain (42%). Lower back pain, contralateral (nonamputated limb) knee pain, and ipsilateral (amputated limb) knee pain were reported by 44%, 38%, and 13% of subjects, respectively. Sixty-five percent of patients were employed or had been employed for multiple years after their war injury. All patients were married, and 97% had children. Fifty-four percent of amputees reported psychological problems; 26% were currently utilizing psychological support services. at long-term follow-up, most military transtibial amputees experienced phantom sensation or some type of stump pain. More than half had persistent psychiatric problems, but only about half of these patients were receiving psychological treatment. Although this case series reports the status of these amputees, the next step would be to prospectively follow modern wartime amputees using standardized, validated outcome measures. With the goal of optimizing long-term amputee outcomes, researchers should correlate outcomes with demographics, injury characteristics, and

Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women

DEFF Research Database (Denmark)

Petäjä, T; Pedersen, Court; Poder, A

2011-01-01

Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered...... of transudation or exudation of serum IgG antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women...... induces long-term systemic and mucosal immune response and has a clinically acceptable safety profile up to four years after the first vaccine dose....

Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women

DEFF Research Database (Denmark)

Petäjä, T; Pedersen, C; Andersen, Anne Poder

2010-01-01

Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered...... of transudation or exudation of serum IgG antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women...... induces long-term systemic and mucosal immune response and has a clinically acceptable safety profile up to four years after the first vaccine dose....

Novel remote electronic medication supply model for opioid-dependent outpatients with polypharmacy--first long-term case study.

Science.gov (United States)

Allemann, Samuel S; Dürsteler, Kenneth M; Strasser, Johannes; Vogel, Marc; Stoeckle, Marcel; Hersberger, Kurt E; Arnet, Isabelle

2017-08-16

Patients with substance use disorders grow older thanks to effective treatments. Together with a high prevalence of comorbidities, psychological problems, and low social support, these patients are at high risk for medication non-adherence. Established treatment facilities face challenges to accommodate these complex patients within their setting. Electronic medication management aids (e-MMAs) might be appropriate to simultaneously monitor and improve adherence for these patients. We report the first long-term experiences with a novel remote electronic medication supply model for two opioid-dependent patients with HIV. John (beginning dementia, 52 years, 6 tablets daily at 12 am) and Mary (frequent drug holidays, 48 years, 5-6 tablets daily at 8 pm) suffered from disease progression due to non-adherence. We electronically monitored adherence and clinical outcomes during 659 (John) and 953 (Mary) days between July 2013 and April 2016. Both patients retrieved over 90% of the pouches within 75 min of the scheduled time. Technical problems occurred in 4% (John) and 7.2% (Mary) of retrievals, but on-site support was seldom required. Viral loads fell below detection limits during the entire observation period. Continuous medication supply and persistence with treatment of over 1.7 years, timing adherence of more than 90%, and suppressed HIV viral load are first results supporting the feasibility of the novel supply model for patients on opioid-assisted treatment and polypharmacy.

Long term storage of virus templated fluorescent materials for sensing applications

Energy Technology Data Exchange (ETDEWEB)

Seetharam, Raviraja N; Guerra, Charles; Satir, Peter [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Blum, Amy Szuchmacher; Soto, Carissa M; Ratna, Banahalli R [Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, 4555 Overlook Avenue SW, Washington, DC 20375 (United States); Whitley, Jessica L [Geo-Centers, Incorporated, Newton, MA 02459 (United States); Sapsford, Kim E [George Mason University, 10910 University Boulevard, Manassas, VA 20110 (United States); Chatterji, Anju; Lin Tianwei; Johnson, John E [Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (United States)], E-mail: amy.blum@nrl.navy.mil

2008-03-12

Wild type, mutant, and chemically modified Cowpea mosaic viruses (CPMV) were studied for long term preservation in the presence and absence of cryoprotectants. Viral complexes were reconstituted and tested via fluorescence spectroscopy and a UV/vis-based RNase assay for structural integrity. When viruses lyophilized in the absence of cryoprotectant were rehydrated and RNase treated, UV absorption increased, indicating that the capsids were damaged. The addition of trehalose during lyophilization protected capsid integrity for at least 7 weeks. Measurements of the fluorescence peak maximum of CPMV lyophilized with trehalose and reconstituted also indicate that the virus remained intact. Microarray binding assays indicated that CPMV particles chemically modified for use as a fluorescent tracer were intact and retained binding specificity after lyophilization in the presence of trehalose. Thus, we demonstrate that functionalized CPMV nanostructures can be stored for the long term, enabling their use in practical sensing applications.

Long term storage of virus templated fluorescent materials for sensing applications

International Nuclear Information System (INIS)

Seetharam, Raviraja N; Guerra, Charles; Satir, Peter; Blum, Amy Szuchmacher; Soto, Carissa M; Ratna, Banahalli R; Whitley, Jessica L; Sapsford, Kim E; Chatterji, Anju; Lin Tianwei; Johnson, John E

2008-01-01

Wild type, mutant, and chemically modified Cowpea mosaic viruses (CPMV) were studied for long term preservation in the presence and absence of cryoprotectants. Viral complexes were reconstituted and tested via fluorescence spectroscopy and a UV/vis-based RNase assay for structural integrity. When viruses lyophilized in the absence of cryoprotectant were rehydrated and RNase treated, UV absorption increased, indicating that the capsids were damaged. The addition of trehalose during lyophilization protected capsid integrity for at least 7 weeks. Measurements of the fluorescence peak maximum of CPMV lyophilized with trehalose and reconstituted also indicate that the virus remained intact. Microarray binding assays indicated that CPMV particles chemically modified for use as a fluorescent tracer were intact and retained binding specificity after lyophilization in the presence of trehalose. Thus, we demonstrate that functionalized CPMV nanostructures can be stored for the long term, enabling their use in practical sensing applications

Differences in the verbal fluency, working memory and executive functions in alcoholics: Short-term vs. long-term abstainers.

Science.gov (United States)

Nowakowska-Domagała, Katarzyna; Jabłkowska-Górecka, Karolina; Mokros, Łukasz; Koprowicz, Jacek; Pietras, Tadeusz

2017-03-01

The aim of the study was to assess differences in verbal fluency, working memory and executive functions in two subgroups of alcohol-dependent patients, those undergoing short-term abstinence (STA) and those undergoing long-term abstinence (LTA), and to compare the level of cognitive functions in patients after long-term abstinence with healthy subjects. The study group consisted of 106 alcohol-dependent patients (53 immediately after drinking at least 3 days and 53 after at least one-year abstinence). The control group comprised 53 subjects, whose age, sex and education levels matched those of the patients in the experimental group. The dependence intensity was assessed using SADD and MAST scales. The neuropsychological assessment was based on the FAS Test, Stroop Test and TMT A&B Test. The results obtained for alcohol-dependent patients revealed significant disturbances of cognitive functions. Such results indicate the presence of severe frontal cerebral cortex dysfunctions. Frontal cortex dysfunctions affecting the verbal fluency and working memory subsystems and the executive functions also persisted during long-term abstinence periods. No significant correlations between the duration of dependence, quantity of alcohol consumed and efficiency of the working memory and executive functions were observed in alcohol-dependent subjects after short-term or long-term abstinence. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children.

NARCIS (Netherlands)

Kyrieleis, H.A.; Lowik, M.M.; Pronk, I.; Cruysberg, J.R.M.; Kremer, J.A.M.; Oyen, W.J.G.; Heuvel, L.P.W.J. van den; Wetzels, J.F.M.; Levtchenko, E.N.

2009-01-01

BACKGROUND AND OBJECTIVES: Frequently relapsing and steroid-dependent minimal-change nephrotic syndrome (MCNS) that originates in childhood can persist after puberty in >20% of patients. These patients require immunosuppressive treatment during several decades of their life. We examined long-term

Congenital infection with atypical porcine pestivirus (APPV) is associated with disease and viral persistence.

Science.gov (United States)

Schwarz, Lukas; Riedel, Christiane; Högler, Sandra; Sinn, Leonie J; Voglmayr, Thomas; Wöchtl, Bettina; Dinhopl, Nora; Rebel-Bauder, Barbara; Weissenböck, Herbert; Ladinig, Andrea; Rümenapf, Till; Lamp, Benjamin

2017-01-06

In 2013, several Austrian piglet-producing farms recorded outbreaks of action-related repetitive myoclonia in newborn piglets ("shaking piglets"). Malnutrition was seen in numerous piglets as a complication of this tremor syndrome. Overall piglet mortality was increased and the number of weaned piglets per sow decreased by more than 10% due to this outbreak. Histological examination of the CNS of affected piglets revealed moderate hypomyelination of the white substance in cerebellum and spinal cord. We detected a recently discovered pestivirus, termed atypical porcine pestivirus (APPV) in all these cases by RT-PCR. A genomic sequence and seven partial sequences were determined and revealed a 90% identity to the US APPV sequences and 92% identity to German sequences. In confirmation with previous reports, APPV genomes were identified in different body fluids and tissues including the CNS of diseased piglets. APPV could be isolated from a "shaking piglet", which was incapable of consuming colostrum, and passaged on different porcine cells at very low titers. To assess the antibody response a blocking ELISA was developed targeting NS3. APPV specific antibodies were identified in sows and in PCR positive piglets affected by congenital tremor (CT). APPV genomes were detected continuously in piglets that gradually recovered from CT, while the antibody titers decreased over a 12-week interval, pointing towards maternally transmitted antibodies. High viral loads were detectable by qRT-PCR in saliva and semen of infected young adults indicating a persistent infection.

Long-term injury in B-lymphocyte precursor cells in repeatedly-irradiated mice

International Nuclear Information System (INIS)

Hendry, J.H.; Clarke, D.; Testa, N.; Kimber, J.

1984-01-01

Mice irradiated with 4 doses of 4,5 Gy X-rays at 3-week intervals, demonstrated long-term proliferative defects in B lymphocytes. There was a reduced mitogenic response to bacterial polysaccharide (30%), a lower concentration (35%) of B-lymphocyte colony-forming cells (BL-CFC) in agar with an increased proportion of clusters (x2), and a reduced concentration (30%) of plaque-forming cells. Grafts of thymocytes were able to restore the levels of BL-CFC in the short term, but in the long term large grafts of femoral marrow cells were much better in restoring the numbers of BL-CFC. The reduced mitogenesis (25%) of splenocytes by concanavalin A and the diminished number of plaque-forming cells, may suggest persistent injury in T-B cell cooperation

Biological effects of petroleum hydrocarbons: Predictions of long-term effects and recovery

International Nuclear Information System (INIS)

Capuzzo, J.M.

1990-01-01

Biological effects of petroleum hydrocarbons on marine organisms and ecosystems are dependent on the persistence and bioavailability of specific hydrocarbons, the ability of organisms to accumulate and metabolize various hydrocarbons, the fate of metabolized products, and the interference of specific hydrocarbons with normal metabolic processes that may alter an organism's chances for survival and reproduction in the environment. In considering the long-term effects of petroleum hydrocarbons on marine ecosystems it is important to ascertain what biological effects may result in subtle ecological changes, changes in community structure and function, and possible impairment of fisheries resources. It is also important to understand which hydrocarbons persist in benthic environments and the sublethal effects that lead to reduced growth, delayed development and reduced reproductive effort, population decline and the loss of that population's function in marine communities. Only through a multi-disciplinary approach to the study of the fate, transport and effects of petroleum hydrocarbons on marine ecosystems will there be a significant improvement in the ability to predict the long-term effects of oil spills and to elucidate the mechanisms of recovery

Issues for the long term management of radioactive waste

Energy Technology Data Exchange (ETDEWEB)

Schneider, T.; Schieber, C. [CEPN, 92 - Fontenay-aux-Roses (France); Lavelle, S. [ICAM, 59 - Lille (France)

2006-07-01

High-level radioactive waste are currently managed in interim storage installations, providing an adequate protection of the public and the workers for the short term period. However, the long-term persistence of the radioactivity of the waste gives a new timescale dimension, never experimented by the society for the development of protection systems. In the framework of the European Commission research project 'COWAM-2' (COmmunity WAste Management) dedicated to the governance of radioactive waste management, the issues of 'long term governance' have been addressed by exploring the elements which can contribute to a better integration of the technical and societal time dimensions, taking into account technical, ethical, economic and organizational considerations. The originality of this project is to address the various issues within working groups involving stakeholders from different origins and European countries together with a research team. After a discussion on the time dimensions to be taken into account from the technical and societal perspective, this paper presents, mainly based on the findings of the COWAM-2 project, a brief analysis of the ethical criteria to be considered when future generations are concerned as well as some performance criteria regarding long term governance. Finally, it proposes a discussion on the interest for the radiation protection experts to engage a process with stakeholders concerned by radioactive waste management in order to favour the emergence of a sustainable management responding to the issues at stake and including radiation protection considerations for long term periods. (authors)

Long-term energy futures: the critical role of technology

International Nuclear Information System (INIS)

Grubler, A.

1999-01-01

The paper briefly reviews the results of a 5-year study conducted by IIASA jointly with the World Energy Council (WEC) on long term-energy perspectives. After summarizing the study's main findings, the paper addresses the crucial role of technological change in the evolution of long-term energy futures and in responding to key long-term uncertainties in the domains of energy demand growth, economics, as well as environmental protection. Based on most recent empirical and methodological findings, long-term dynamics of technological change portray a number of distinct features that need to be taken account of in technology and energy policy. First, success of innovation efforts and ultimate outcomes of technological are uncertain. Second, new, improved technologies are not a free good, but require continued dedicated efforts. Third, technological knowledge (as resulting from R and D and accumulation of experience, i.e. technological learning) exhibits characteristics of (uncertain) increasing returns. Forth, due to innovation - diffusion lags, technological interdependence, and infrastructure needs (network externalities), rates of change in large-scale energy systems are necessarily slow. This implies acting sooner rather than later as a contigency policy to respond to long-term social, economic and environmental uncertainties, most notably possible climate change. Rather than picking technological 'winners' the results of the IIASA-WEC scenario studies are seen most appropriate to guide technology and R and D portfolio analysis. Nonetheless, robust persistent patterns of technological change invariably occur across all scenarios. Examples of primising groups of technologies are given. The crucial importance of meeting long-energy demand in developing countries, assuring large-scale infrastructure investments, maintaining a strong and diversified R AND D protfolio, as well as to dvise new institutional mechnisms for technology development and diffusion for instance

Peripheral immunophenotype and viral promoter variants during the asymptomatic phase of feline immunodeficiency virus infection.

Science.gov (United States)

Murphy, B; Hillman, C; McDonnel, S

2014-01-22

Feline immunodeficiency virus (FIV)-infected cats enter a clinically asymptomatic phase during chronic infection. Despite the lack of overt clinical disease, the asymptomatic phase is characterized by persistent immunologic impairment. In the peripheral blood obtained from cats experimentally infected with FIV-C for approximately 5 years, we identified a persistent inversion of the CD4/CD8 ratio. We cloned and sequenced the FIV-C long terminal repeat containing the viral promoter from cells infected with the inoculating virus and from in vivo-derived peripheral blood mononuclear cells and CD4 T cells isolated at multiple time points throughout the asymptomatic phase. Relative to the inoculating virus, viral sequences amplified from cells isolated from all of the infected animals demonstrated multiple single nucleotide mutations and a short deletion within the viral U3, R and U5 regions. A transcriptionally inactivating proviral mutation in the U3 promoter AP-1 site was identified at multiple time points from all of the infected animals but not within cell-associated viral RNA. In contrast, no mutations were identified within the sequence of the viral dUTPase gene amplified from PBMC isolated at approximately 5 years post-infection relative to the inoculating sequence. The possible implications of these mutations to viral pathogenesis are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Long-term follow-up of HIV-1-infected adults who received the F4/AS01B HIV-1 vaccine candidate in two randomised controlled trials.

Science.gov (United States)

Harrer, Thomas; Dinges, Warren; Roman, François

2018-05-03

This Phase I/II, open, long-term follow-up study was conducted in antiretroviral therapy (ART)-naïve (N = 212) and ART-treated (N = 19) human immunodeficiency virus 1 (HIV-1)-infected adults, who received an HIV-1 investigational vaccine (F4/AS01 B ) or placebo in two previous studies (NCT00814762 and NCT01218113). After a minimum of two years and a maximum of four years of follow-up post-vaccination per patient, no significant differences were observed between F4/AS01 B and placebo groups in terms of viral load, CD4 + T-cell count and incidence of specific clinical events. Vaccine-induced polyfunctional CD4 + T-cells persisted up to study end and no relevant vaccine-related safety events were reported in F4/AS01 B groups. This study has been registered at ClinicalTrials.gov (NCT01092611). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Audit of long-term and short-term liabilities

Directory of Open Access Journals (Sweden)

Korinko M.D.

2017-03-01

Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

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.

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.

Long-term follow-up study and long-term care of childhood cancer survivors

Directory of Open Access Journals (Sweden)

Hyeon Jin Park

2010-04-01

Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

Relative phase asynchrony and long-range correlation of long-term solar magnetic activity

Science.gov (United States)

Deng, Linhua

2017-07-01

Statistical signal processing is one of the most important tasks in a large amount of areas of scientific studies, such as astrophysics, geophysics, and space physics. Phase recurrence analysis and long-range persistence are the two dynamical structures of the underlying processes for the given natural phenomenon. Linear and nonlinear time series analysis approaches (cross-correlation analysis, cross-recurrence plot, wavelet coherent transform, and Hurst analysis) are combined to investigate the relative phase interconnection and long-range correlation between solar activity and geomagnetic activity for the time interval from 1932 January to 2017 January. The following prominent results are found: (1) geomagnetic activity lags behind sunspot numbers with a phase shift of 21 months, and they have a high level of asynchronous behavior; (2) their relative phase interconnections are in phase for the periodic scales during 8-16 years, but have a mixing behavior for the periodic belts below 8 years; (3) both sunspot numbers and geomagnetic activity can not be regarded as a stochastic phenomenon because their dynamical behaviors display a long-term correlation and a fractal nature. We believe that the presented conclusions could provide further information on understanding the dynamical coupling of solar dynamo process with geomagnetic activity variation, and the crucial role of solar and geomagnetic activity in the long-term climate change.

HTLV-1 Alters T Cells for Viral Persistence and Transmission

Directory of Open Access Journals (Sweden)

Azusa Tanaka

2018-03-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 was the first retrovirus to be discovered as a causative agent of adult T-cell leukemia-lymphoma (ATL and chronic inflammatory diseases. Two viral factors, Tax and HTLV-1 bZIP factor (HBZ, are thought to be involved in the leukemogenesis of ATL. Tax expression is frequently lost due to DNA methylation in the promoter region, genetic changes to the tax gene, and deletion of the 5′ long terminal repeat (LTR in approximately half of all ATL cases. On the other hand, HBZ is expressed in all ATL cases. HBZ is known to function in both protein form and mRNA form, and both forms play an important role in the oncogenic process of HTLV-1. HBZ protein has a variety of functions, including the suppression of apoptosis, the promotion of proliferation, and the impairment of anti-viral activity, through the interaction with several host cellular proteins including p300/CBP, Foxp3, and Foxo3a. These functions dramatically modify the transcriptional profiling of host T cells. HBZ mRNA also promotes T cell proliferation and viability. HBZ changes infected T cells to CCR4+TIGIT+CD4+ effector/memory T cells. This unique immunophenotype enables T cells to migrate into various organs and tissues and to survive in vivo. In this review, we summarize how HBZ hijacks the transcriptional networks and immune systems of host T cells to contribute to HTLV-1 pathogenesis on the basis of recent new findings about HBZ and tax.

Long-term prevention of diabetic nephropathy: an audit

DEFF Research Database (Denmark)

Schjoedt, K.J.; Hansen, H.P.; Tarnow, L.

2008-01-01

AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin......-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in microalbuminuric type 1 diabetic patients on progression of microalbuminuria and development of DN. METHODS: All patients with type 1 diabetes and persistent microalbuminuria (30-300 mg/24 h) were identified (n=227...

Immediate and persistent transcriptional correlates of long-term sensitization training at different CNS loci in Aplysia californica.

Directory of Open Access Journals (Sweden)

Samantha Herdegen

Full Text Available Repeated noxious stimulation produces long-term sensitization of defensive withdrawal reflexes in Aplysia californica, a form of long-term memory that requires changes in both transcription and translation. Previous work has identified 10 transcripts which are rapidly up-regulated after long-term sensitization training in the pleural ganglia. Here we use quantitative PCR to begin examining how these transcriptional changes are expressed in different CNS loci related to defensive withdrawal reflexes at 1 and 24 hours after long-term sensitization training. Specifically, we sample from a the sensory wedge of the pleural ganglia, which exclusively contains the VC nociceptor cell bodies that help mediate input to defensive withdrawal circuits, b the remaining pleural ganglia, which contain withdrawal interneurons, and c the pedal ganglia, which contain many motor neurons. Results from the VC cluster show different temporal patterns of regulation: 1 rapid but transient up-regulation of Aplysia homologs of C/EBP, C/EBPγ, and CREB1, 2 delayed but sustained up-regulation of BiP, Tolloid/BMP-1, and sensorin, 3 rapid and sustained up-regulation of Egr, GlyT2, VPS36, and an uncharacterized protein (LOC101862095, and 4 an unexpected lack of regulation of Aplysia homologs of calmodulin (CaM and reductase-related protein (RRP. Changes in the remaining pleural ganglia mirror those found in the VC cluster at 1 hour but with an attenuated level of regulation. Because these samples had almost no expression of the VC-specific transcript sensorin, our data suggests that sensitization training likely induces transcriptional changes in either defensive withdrawal interneurons or neurons unrelated to defensive withdrawal. In the pedal ganglia, we observed only a rapid but transient increase in Egr expression, indicating that long-term sensitization training is likely to induce transcriptional changes in motor neurons but raising the possibility of different

Long-term adherence to a local guideline on postoperative body temperature measurement: mixed methods analysis

NARCIS (Netherlands)

Storm-Versloot, Marja N.; Knops, Anouk M.; Ubbink, Dirk T.; Goossens, Astrid; Legemate, Dink A.; Vermeulen, Hester

2012-01-01

Aim To find out whether a successful multifaceted implementation approach of a local evidence-based guideline on postoperative body temperature measurements (BTM) was persistent over time, and which factors influenced long-term adherence. Methods Mixed methods analysis. Patient records were

Gastrointestinal Symptoms in Celiac Disease Patients on a Long-Term Gluten-Free Diet.

Science.gov (United States)

Laurikka, Pilvi; Salmi, Teea; Collin, Pekka; Huhtala, Heini; Mäki, Markku; Kaukinen, Katri; Kurppa, Kalle

2016-07-14

Experience suggests that many celiac patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD). We investigated the prevalence and severity of these symptoms in patients with variable duration of GFD. Altogether, 856 patients were classified into untreated (n = 128), short-term GFD (1-2 years, n = 93) and long-term GFD (≥3 years, n = 635) groups. Analyses were made of clinical and histological data and dietary adherence. Symptoms were evaluated by the validated GSRS questionnaire. One-hundred-sixty healthy subjects comprised the control group. Further, the severity of symptoms was compared with that in peptic ulcer, reflux disease, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Altogether, 93% of the short-term and 94% of the long-term treated patients had a strict GFD and recovered mucosa. Untreated patients had more diarrhea, indigestion and abdominal pain than those on GFD and controls. There were no differences in symptoms between the short- and long-term GFD groups, but both yielded poorer GSRS total score than controls (p = 0.03 and p = 0.05, respectively). Furthermore, patients treated 1-2 years had more diarrhea (p = 0.03) and those treated >10 years more reflux (p = 0.04) than controls. Long-term treated celiac patients showed relatively mild symptoms compared with other gastrointestinal diseases. Based on our results, good response to GFD sustained in long-term follow-up, but not all patients reach the level of healthy individuals.

Cognitive, physical, and mental health outcomes between long-term cannabis and tobacco users.

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Lovell, M E; Bruno, R; Johnston, J; Matthews, A; McGregor, I; Allsop, D J; Lintzeris, N

2018-04-01

Cannabis intoxication adversely affects health, yet persistent effects following short-term abstinence in long-term cannabis users are unclear. This matched-subjects, cross-sectional study compared health outcomes of long-term cannabis and long-term tobacco-only users, relative to population norms. Nineteen long-term (mean 32.3years of use, mean age 55.7years), abstinent (mean 15h) cannabis users and 16 long-term tobacco users (mean 37.1years of use, mean age 52.9years), matched for age, educational attainment, and lifetime tobacco consumption, were compared on measures of learning and memory, response inhibition, information-processing, sustained attention, executive control, and mental and physical health. Cannabis users exhibited poorer overall learning and delayed recall and greater interference and forgetting than tobacco users, and exhibited poorer recall than norms. Inhibition and executive control were similar between groups, but cannabis users had slower reaction times during information processing and sustained attention tasks. Cannabis users had superior health satisfaction and psychological, somatic, and general health than tobacco users and had similar mental and physical health to norms whilst tobacco users had greater stress, role limitations from emotional problems, and poorer health satisfaction. Long-term cannabis users may exhibit deficits in some cognitive domains despite short-term abstinence and may therefore benefit from interventions to improve cognitive performance. Tobacco alone may contribute to adverse mental and physical health outcomes, which requires appropriate control in future studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-term follow-up of cognitive outcome after breech presentation at birth

DEFF Research Database (Denmark)

Sørensen, Henrik Toft; Steffensen, Flemming Hald; Olsen, Jørn

1999-01-01

Studies of long-term consequences of birth in breech presentation are sparse. Therefore, we conducted a cohort study linking birth registry data with data collected during evaluation for military service in 4,298 conscripts born between 1973 and 1976. The cognitive functions were measured...... with the Boerge Prien IQ test. A total of 164 conscripts were born in breech presentation and 70 (42.7%) of these were delivered after Caesarean section. The mean Boerge Prien test score was 43.2 among men born in cephalic presentation and 39.9 among those born in breech presentation for a difference of 3.3 (95......% confidence interval = 1.8-4.7). The negative association between breech presentation and cognitive outcome persisted after stratifying by Caesarean section and after adjustment for confounders. It also persisted when we restricted the analyses to term singleton pregnancies....

Alterations in adaptive immunity persist during long-duration spaceflight

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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

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 ...

[Long-term psychiatric hospitalizations].

Science.gov (United States)

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Exploring viral reservoir: The combining approach of cell sorting and droplet digital PCR.

Science.gov (United States)

Gibellini, Lara; Pecorini, Simone; De Biasi, Sara; Pinti, Marcello; Bianchini, Elena; De Gaetano, Anna; Digaetano, Margherita; Pullano, Rosalberta; Lo Tartaro, Domenico; Iannone, Anna; Mussini, Cristina; Cossarizza, Andrea; Nasi, Milena

2018-02-01

Combined antiretroviral therapy (cART) blocks different steps of HIV replication and maintains plasma viral RNA at undetectable levels. The virus can remain in long-living cells and create a reservoir where HIV can restart replicating after cART discontinuation. A persistent viral production triggers and maintains a persistent immune activation, which is a well-known feature of chronic HIV infection, and contributes either to precocious aging, or to the increased incidence of morbidity and mortality of HIV positive patients. The new frontier of the treatment of HIV infection is nowadays eradication of the virus from all host cells and tissues. For this reason, it is crucial to have a clear and precise idea of where the virus hides, and which are the cells that keep it silent. Important efforts have been made to improve the detection of viral reservoirs, and new techniques are now giving the opportunity to characterize viral reservoirs. Among these techniques, a strategic approach based upon cell sorting and droplet digital PCR (ddPCR) is opening new horizons and opportunities of research. This review provides an overview of the methods that combine cell sorting and ddPCR for the quantification of HIV DNA in different cell types, and for the detection of its maintenance. Copyright © 2017 Elsevier Inc. All rights reserved.

Persistent Bovine Viral Diarrhea Virus infection in domestic and wild small ruminants and camelids including the mountain goat (Oreamnos americanus

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Danielle Darracq Nelson

2016-01-01

Full Text Available Bovine viral diarrhea virus (BVDV is a Pestivirus best known for causing a variety of disease syndromes in cattle, including gastrointestinal disease, reproductive insufficiency, immunosuppression, mucosal disease, and hemorrhagic syndrome. The virus can be spread by transiently infected individuals and by persistently infected animals that may be asymptomatic while shedding large amounts of virus throughout their lifetime. BVDV has been reported in over 40 domestic and free-ranging species, and persistent infection has been described in eight of those species: white-tailed deer, mule deer, eland, mousedeer, mountain goats, alpacas, sheep, and domestic swine. This paper reviews the various aspects of BVDV transmission, disease syndromes, diagnosis, control, and prevention, as well as examines BVDV infection in domestic and wild small ruminants and camelids including mountain goats (Oreamnos americanus.

Age and long-term protective immunity in dogs and cats.

Science.gov (United States)

Schultz, R D; Thiel, B; Mukhtar, E; Sharp, P; Larson, L J

2010-01-01

Vaccination can provide an immune response that is similar in duration to that following a natural infection. In general, adaptive immunity to viruses develops earliest and is highly effective. Such anti-viral immune responses often result in the development of sterile immunity and the duration of immunity (DOI) is often lifelong. In contrast, adaptive immunity to bacteria, fungi or parasites develops more slowly and the DOI is generally short compared with most systemic viral infections. Sterile immunity to these infectious agents is less commonly engendered. Old dogs and cats rarely die from vaccine-preventable infectious disease, especially when they have been vaccinated and immunized as young adults (i.e. between 16 weeks and 1 year of age). However, young animals do die, often because vaccines were either not given or not given at an appropriate age (e.g. too early in life in the presence of maternally derived antibody [MDA]). More animals need to be vaccinated to increase herd (population) immunity. The present study examines the DOI for core viral vaccines in dogs that had not been revaccinated for as long as 9 years. These animals had serum antibody to canine distemper virus (CDV), canine parvovirus type 2 (CPV-2) and canine adenovirus type-1 (CAV-1) at levels considered protective and when challenged with these viruses, the dogs resisted infection and/or disease. Thus, even a single dose of modified live virus (MLV) canine core vaccines (against CDV, cav-2 and cpv-2) or MLV feline core vaccines (against feline parvovirus [FPV], feline calicivirus [FCV] and feline herpesvirus [FHV]), when administered at 16 weeks or older, could provide long-term immunity in a very high percentage of animals, while also increasing herd immunity. Copyright 2009 Elsevier Ltd. All rights reserved.

Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

Science.gov (United States)

Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

2007-09-01

In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

Science.gov (United States)

Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

2014-01-01

Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

a Method for the Extraction of Long-Term Deformation Characteristics of Long-Span High-Speed Railway Bridges Using High-Resolution SAR Images

Science.gov (United States)

Jia, H. G.; Liu, L. Y.

2016-06-01

Natural causes and high-speed train load will result in the structural deformation of long-span bridges, which greatly influence the safety operation of high-speed railway. Hence it is necessary to conduct the deformation monitoring and regular status assessment for long-span bridges. However for some traditional surveying technique, e.g. control-point-based surveying techniques, a lot of human and material resources are needed to perform the long-term monitoring for the whole bridge. In this study we detected the long-term bridge deformation time-series by persistent scatterer interferometric synthetic aperture radar (PSInSAR) technique using the high-resolution SAR images and external digital elevation model. A test area in Nanjing city in China is chosen and TerraSAR-X images and Tandem-X for this area have been used. There is the Dashengguan bridge in high speed railway in this area as study object to evaluate this method. Experiment results indicate that the proposed method can effectively extract the long-term deformation of long-span high-speed railway bridge with higher accuracy.

A METHOD FOR THE EXTRACTION OF LONG-TERM DEFORMATION CHARACTERISTICS OF LONG-SPAN HIGH-SPEED RAILWAY BRIDGES USING HIGH-RESOLUTION SAR IMAGES

Directory of Open Access Journals (Sweden)

H. G. Jia

2016-06-01

Full Text Available Natural causes and high-speed train load will result in the structural deformation of long-span bridges, which greatly influence the safety operation of high-speed railway. Hence it is necessary to conduct the deformation monitoring and regular status assessment for long-span bridges. However for some traditional surveying technique, e.g. control-point-based surveying techniques, a lot of human and material resources are needed to perform the long-term monitoring for the whole bridge. In this study we detected the long-term bridge deformation time-series by persistent scatterer interferometric synthetic aperture radar (PSInSAR technique using the high-resolution SAR images and external digital elevation model. A test area in Nanjing city in China is chosen and TerraSAR-X images and Tandem-X for this area have been used. There is the Dashengguan bridge in high speed railway in this area as study object to evaluate this method. Experiment results indicate that the proposed method can effectively extract the long-term deformation of long-span high-speed railway bridge with higher accuracy.

Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

Science.gov (United States)

Smolen, Paul; Baxter, Douglas A; Byrne, John H

2012-01-01

Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

Long-term potentiation and long-term depression: a clinical perspective

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Timothy V.P. Bliss

2011-01-01

Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia.

Science.gov (United States)

Chen, Shanping; Cai, Diancai; Pearce, Kaycey; Sun, Philip Y-W; Roberts, Adam C; Glanzman, David L

2014-11-17

Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories.

Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus

Directory of Open Access Journals (Sweden)

Ana Cristina Cisne Frota

Full Text Available Abstract Objective: HIV-infected individuals (HIVI are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA after a meningococcal C conjugate (MCC vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. Methods: HIVI and HIV uninfected individuals (HIVU, aged 2–18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4 at baseline and at 12–18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. Results: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value = 0.02. 85 HIVI (44% had undetectable viral load (UVL. Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12–18 months after immunization (p = 0.14. Baseline immunity (odds ratio [OR] = 70.70, 95% CI: 65.2–766.6; UVL at entry (OR: 2.87, 95% CI: 0.96–8.62 and lower family income (OR: 0.09, 95% CI: 0.01–0.69 were associated with seroprotection among HIVI. Conclusion: Seroprotection at 12–18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.

Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.

Science.gov (United States)

Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

2016-04-13

The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal

Long term results of childhood dysphonia treatment.

Science.gov (United States)

Mackiewicz-Nartowicz, Hanna; Sinkiewicz, Anna; Bielecka, Arleta; Owczarzak, Hanna; Mackiewicz-Milewska, Magdalena; Winiarski, Piotr

2014-05-01

The aim of this study was to assess the long term results of treatment and rehabilitation of childhood dysphonia. This study included a group of adolescents (n=29) aged from 15 to 20 who were treated due to pediatric hyperfunctional dysphonia and soft vocal fold nodules during their pre-mutational period (i.e. between 5 and 12 years of age). The pre-mutational therapy was comprised of proper breathing pattern training, voice exercises and psychological counseling. Laryngostroboscopic examination and perceptual analysis of voice were performed in each patient before treatment and one to four years after mutation was complete. The laryngostroboscopic findings, i.e. symmetry, amplitude, mucosal wave and vocal fold closure, were graded with NAPZ scale, and the GRBAS scale was used for the perceptual voice analysis. Complete regression of the childhood dysphonia was observed in all male patients (n=14). Voice disorders regressed completely also in 8 out of 15 girls, but symptoms of dysphonia documented on perceptual scale persisted in the remaining seven patients. Complex voice therapy implemented in adolescence should be considered as either the treatment or preventive measure of persistent voice strain, especially in girls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Antimicrobial stewardship in long term care facilities: what is effective?

Science.gov (United States)

Nicolle, Lindsay E

2014-02-12

Intense antimicrobial use in long term care facilities promotes the emergence and persistence of antimicrobial resistant organisms and leads to adverse effects such as C. difficile colitis. Guidelines recommend development of antimicrobial stewardship programs for these facilities to promote optimal antimicrobial use. However, the effectiveness of these programs or the contribution of any specific program component is not known. For this review, publications describing evaluation of antimicrobial stewardship programs for long term care facilities were identified through a systematic literature search. Interventions included education, guidelines development, feedback to practitioners, and infectious disease consultation. The studies reviewed varied in types of facilities, interventions used, implementation, and evaluation. Comprehensive programs addressing all infections were reported to have improved antimicrobial use for at least some outcomes. Targeted programs for treatment of pneumonia were minimally effective, and only for indicators of uncertain relevance for stewardship. Programs focusing on specific aspects of treatment of urinary infection - limiting treatment of asymptomatic bacteriuria or prophylaxis of urinary infection - were reported to be effective. There were no reports of cost-effectiveness, and the sustainability of most of the programs is unclear. There is a need for further evaluation to characterize effective antimicrobial stewardship for long term care facilities.

Detection of human parvovirus 4 viremia in the follow-up blood samples from seropositive individuals suggests the existence of persistent viral replication or reactivation of latent viral infection.

Science.gov (United States)

Chen, Mao-Yuan; Hung, Chien-Ching; Lee, Kuang-Lun

2015-06-19

The transmission routes for human parvovirus 4 (PARV4) infections in areas with high seroprevalence are not known. In the work described here, persistent PARV4 viral replication was investigated by conducting a longitudinal study. Ten healthcare workers each provided a blood sample at the beginning of the study (first sample) and 12 months later (second sample). The paired samples were tested for PARV4-positivity by immunoblotting analysis and nested polymerase chain reactions. IgG antibodies against PARV4 were detected in six participants, three of whom also had IgM antibodies against PARV4. The immunoblotting results did not vary over time. PARV4 DNA was detected in the first blood sample from one participant who had IgG antibodies against PARV4 and in the second blood samples from 2 participants who had IgG and IgM antibodies against PARV4. Detection of PARV4 DNA in the second blood samples from two seropositive participants suggests the existence of persistent PARV4 replication or reactivation of inactive virus in the tissues. The finding of persistent or intermittent PARV4 replication in individuals with past infections provides an important clue toward unraveling the non-parenteral transmission routes of PARV4 infection in areas where the virus is endemic.

Long-Term Symbolic Learning

National Research Council Canada - National Science Library

Kennedy, William G; Trafton, J. G

2007-01-01

What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation.

Science.gov (United States)

McCoy, Portia; Norton, Thomas T; McMahon, Lori L

2008-07-01

Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

Pediatric polytrauma : Short-term and long-term outcomes

NARCIS (Netherlands)

vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

Long-term effectiveness of highly active antiretroviral therapy (HAART) in perinatally HIV-infected children in Denmark

DEFF Research Database (Denmark)

Bracher, Linda; Valerius, Niels Henrik; Rosenfeldt, Vibeke

2007-01-01

children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline......The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients ... characteristics were median CD4 percentage 14% and HIV-RNA viral load 4.9 log(10). Within the first 12 weeks of therapy approximately 60% achieved HIV-RNA viral load children changed the components of HAART. The proportion of children with CD4...

Long persistence of rigor mortis at constant low temperature.

Science.gov (United States)

Varetto, Lorenzo; Curto, Ombretta

2005-01-06

We studied the persistence of rigor mortis by using physical manipulation. We tested the mobility of the knee on 146 corpses kept under refrigeration at Torino's city mortuary at a constant temperature of +4 degrees C. We found a persistence of complete rigor lasting for 10 days in all the cadavers we kept under observation; and in one case, rigor lasted for 16 days. Between the 11th and the 17th days, a progressively increasing number of corpses showed a change from complete into partial rigor (characterized by partial bending of the articulation). After the 17th day, all the remaining corpses showed partial rigor and in the two cadavers that were kept under observation "à outrance" we found the absolute resolution of rigor mortis occurred on the 28th day. Our results prove that it is possible to find a persistence of rigor mortis that is much longer than the expected when environmental conditions resemble average outdoor winter temperatures in temperate zones. Therefore, this datum must be considered when a corpse is found in those environmental conditions so that when estimating the time of death, we are not misled by the long persistence of rigor mortis.

Forecasting long memory time series under a break in persistence

DEFF Research Database (Denmark)

Heinen, Florian; Sibbertsen, Philipp; Kruse, Robinson

We consider the problem of forecasting time series with long memory when the memory parameter is subject to a structural break. By means of a large-scale Monte Carlo study we show that ignoring such a change in persistence leads to substantially reduced forecasting precision. The strength...... of this effect depends on whether the memory parameter is increasing or decreasing over time. A comparison of six forecasting strategies allows us to conclude that pre-testing for a change in persistence is highly recommendable in our setting. In addition we provide an empirical example which underlines...

Prior Virus Exposure Alters the Long-Term Landscape of Viral Replication during Feline Lentiviral Infection

Directory of Open Access Journals (Sweden)

Sue VandeWoude

2011-10-01

Full Text Available We developed a feline model of lentiviral cross-species transmission using a puma lentivirus (PLV or FIVPco which infects domestic cats but does not cause disease. Infection with PLV protects cats from CD4+ T-cell decline caused by subsequent infection with virulent feline immunodeficiency virus (FIV. Previous studies implicate innate immune and/or cellular restriction mechanisms for FIV disease attenuation in PLV-infected cats. In this study, we evaluated viral infection and cytokine mRNA transcription in 12 different tissue reservoirs approximately five months post infection. We quantitated tissue proviral load, viral mRNA load and relative transcription of IL-10, IL-12p40 and IFNγ from tissues of cats exposed to FIV, PLV or both viruses and analyzed these parameters using a multivariate statistical approach. The distribution and intensity of FIV infection and IFNγ transcription differed between single and co-infected cats, characterized by higher FIV proviral loads and IFNγ expression in co-infected cat tissues. Variability in FIV mRNA load and IFNγ was significantly more constrained in co-infected versus singly infected cat tissues. Single-infected:co-infected ratios of FIV mRNA load compared to FIV proviral load indicated that active viral transcription was apparently inhibited during co-infection. These results indicate that previous PLV infection increases activation of tissue innate immunity and constrains the ability of FIV to productively infect tissue reservoirs of infection for months, independent of FIV proviral load, supporting a model in which innate immunity and/or modulation of target cell susceptibility play a key role in PLV-induced protection from FIV disease.

Long-term competence restoration.

Science.gov (United States)

Morris, Douglas R; DeYoung, Nathaniel J

2014-01-01

While the United States Supreme Court's Jackson v. Indiana decision and most state statutes mandate determinations of incompetent defendants' restoration probabilities, courts and forensic clinicians continue to lack empirical evidence to guide these determinations and do not yet have a consensus regarding whether and under what circumstances incompetent defendants are restorable. The evidence base concerning the restoration likelihood of those defendants who fail initial restoration efforts is even further diminished and has largely gone unstudied. In this study, we examined the disposition of a cohort of defendants who underwent long-term competence restoration efforts (greater than six months) and identified factors related to whether these defendants were able to attain restoration and adjudicative success. Approximately two-thirds (n = 52) of the 81 individuals undergoing extended restoration efforts were eventually deemed restored to competence. Lengths of hospitalization until successful restoration are presented with implications for the reasonable length of time that restoration efforts should persist. Older individuals were less likely to be restored and successfully adjudicated, and individuals with more severe charges and greater factual legal understanding were more likely to be restored and adjudicated. The significance of these findings for courts and forensic clinicians is discussed.

Non-polarized cytokine profile of a long-term non-progressor HIV infected patient.

Science.gov (United States)

Pina, Ana Flávia; Matos, Vanessa Terezinha Gubert de; Bonin, Camila Mareti; Dal Fabbro, Márcia Maria Ferrairo Janini; Tozetti, Inês Aparecida

The HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without antiretroviral therapy. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast IL-4 was identified. Host-related factors could help explain such a level of infection control, namely the differentiated modulation of the cellular immune response and a non-polarized cytokine response of the TH1 and TH2 profiles. Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

Directory of Open Access Journals (Sweden)

Geovanny F. Perez

2016-10-01

Full Text Available Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children. Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks, 12% in preterm (32–37 weeks and 21% in severely premature children (<32 weeks. The most common viruses identified were rhinovirus (RV; 60% and respiratory syncytial virus (RSV; 17%. Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.

Effects of interferon on cultured cells persistently infected with viruses

Energy Technology Data Exchange (ETDEWEB)

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.

Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma.

Science.gov (United States)

Yii, A C A; Tan, J H Y; Lapperre, T S; Chan, A K W; Low, S Y; Ong, T H; Tan, K L; Chotirmall, S H; Sterk, P J; Koh, M S

2017-09-01

Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment. To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory. Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory. Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m 2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort. Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently

Does computer use pose a hazard for future long-term sickness absence?

DEFF Research Database (Denmark)

Andersen, Johan Hviid; Mikkelsen, Sigurd

2010-01-01

. The hazard ratio for sickness absence with weekly increase of one hour in computer use was 0.99 (95% CI: 0.99 to 1.00). Low satisfaction with work place arrangements and female gender both doubled the risk of sickness absence.We have earlier found that computer use did not predict persistent pain in the neck...... and upper limb, and it seems that computer use neither predicts future long-term sickness absence of all causes....

Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats

OpenAIRE

Sandhu, M. S.; Lee, K. Z.; Fregosi, R. F.; Fuller, D. D.

2010-01-01

Intermittent hypoxia (IH) can induce a persistent increase in neural drive to the respiratory muscles known as long-term facilitation (LTF). LTF of phrenic inspiratory activity is often studied in anesthetized animals after phrenicotomy (PhrX), with subsequent recordings being made from the proximal stump of the phrenic nerve. However, severing afferent and efferent axons in the phrenic nerve has the potential to alter the excitability of phrenic motoneurons, which has been hypothesized to be...

Near-Term Actions to Address Long-Term Climate Risk

Science.gov (United States)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

Directory of Open Access Journals (Sweden)

Paul Smolen

Full Text Available Protein synthesis-dependent, late long-term potentiation (LTP and depression (LTD at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

Long Term Financing of Infrastructure

OpenAIRE

Sinha, Sidharth

2014-01-01

Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

Requirement for nuclear calcium signaling in Drosophila long-term memory.

Science.gov (United States)

Weislogel, Jan-Marek; Bengtson, C Peter; Müller, Michaela K; Hörtzsch, Jan N; Bujard, Martina; Schuster, Christoph M; Bading, Hilmar

2013-05-07

Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

F-Specific RNA Bacteriophages, Especially Members of Subgroup II, Should Be Reconsidered as Good Indicators of Viral Pollution of Oysters.

Science.gov (United States)

Hartard, C; Leclerc, M; Rivet, R; Maul, A; Loutreul, J; Banas, S; Boudaud, N; Gantzer, C

2018-01-01

Norovirus (NoV) is the leading cause of gastroenteritis outbreaks linked to oyster consumption. In this study, we investigated the potential of F-specific RNA bacteriophages (FRNAPH) as indicators of viral contamination in oysters by focusing especially on FRNAPH subgroup II (FRNAPH-II). These viral indicators have been neglected because their behavior is sometimes different from that of NoV in shellfish, especially during the depuration processes usually performed before marketing. However, a significant bias needs to be taken into account. This bias is that, in the absence of routine culture methods, NoV is targeted by genome detection, while the presence of FRNAPH is usually investigated by isolation of infectious particles. In this study, by targeting both viruses using genome detection, a significant correlation between the presence of FRNAPH-II and that of NoV in shellfish collected from various European harvesting areas impacted by fecal pollution was observed. Moreover, during their depuration, while the long period of persistence of NoV was confirmed, a similar or even longer period of persistence of the FRNAPH-II genome, which was over 30 days, was observed. Such a striking genome persistence calls into question the relevance of molecular methods for assessing viral hazards. Targeting the same virus (i.e., FRNAPH-II) by culture and genome detection in specimens from harvesting areas as well as during depuration, we concluded that the presence of genomes in shellfish does not provide any information on the presence of the corresponding infectious particles. In view of these results, infectious FRNAPH detection should be reconsidered as a valuable indicator in oysters, and its potential for use in assessing viral hazard needs to be investigated. IMPORTANCE This work brings new data about the behavior of viruses in shellfish, as well as about the relevance of molecular methods for their detection and evaluation of the viral hazard. First, a strong

APOBEC3 Interference during Replication of Viral Genomes

Directory of Open Access Journals (Sweden)

Luc Willems

2015-06-01

Full Text Available Co-evolution of viruses and their hosts has reached a fragile and dynamic equilibrium that allows viral persistence, replication and transmission. In response, infected hosts have developed strategies of defense that counteract the deleterious effects of viral infections. In particular, single-strand DNA editing by Apolipoprotein B Editing Catalytic subunits proteins 3 (APOBEC3s is a well-conserved mechanism of mammalian innate immunity that mutates and inactivates viral genomes. In this review, we describe the mechanisms of APOBEC3 editing during viral replication, the viral strategies that prevent APOBEC3 activity and the consequences of APOBEC3 modulation on viral fitness and host genome integrity. Understanding the mechanisms involved reveals new prospects for therapeutic intervention.

Costs and longer-term savings of parenting programmes for the prevention of persistent conduct disorder: a modelling study

Directory of Open Access Journals (Sweden)

Beecham Jennifer

2011-10-01

Full Text Available Abstract Background Conduct disorders are the most common psychiatric disorders in children and may persist into adulthood in about 50% of cases. The costs to society are high and impact many public sector agencies. Parenting programmes have been shown to positively affect child behaviour, but little is known about their potential long-term cost-effectiveness. We therefore estimate the costs of and longer-term savings from evidence-based parenting programmes for the prevention of persistent conduct disorder. Methods A decision-analytic Markov model compares two scenarios: 1 a 5-year old with clinical conduct disorder receives an evidence-based parenting programme; 2 the same 5-year old does not receive the programme. Cost-savings analysis is performed by comparing the probability that conduct disorder persists over time in each scenario, adopting both a public sector and a societal perspective. If the intervention is successful in reducing persistent conduct disorder, cost savings may arise from reduced use of health services, education support, social care, voluntary agencies and from crimes averted. Results Results strongly suggest that parenting programmes reduce the chance that conduct disorder persists into adulthood and are cost-saving to the public sector within 5-8 years under base case conditions. Total savings to society over 25 years are estimated at £16,435 per family, which compares with an intervention cost in the range of £952-£2,078 (2008/09 prices. Conclusions Effective implementation of evidence-based parenting programmes is likely to yield cost savings to the public sector and society. More research is needed to address evidence gaps regarding the current level of provision, longer-term effectiveness and questions of implementation, engagement and equity.

Long-term effects of burning on woody plant species sprouting on the False thornveld of Eastern Cape

CSIR Research Space (South Africa)

Ratsele, C

2010-11-01

Full Text Available Sprouting allows woody plant species to persist in a site after a wide range of disturbances (e.g. prolonged fire), where opportunities for seedling establishment are limited. A study to investigate long-term effects of fire sprouting of woody...

Long term stability of power systems

Energy Technology Data Exchange (ETDEWEB)

Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

1994-12-31

Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

Cytopathic bovine viral diarrhea viruses (BVDV): emerging pestiviruses doomed to extinction.

Science.gov (United States)

Peterhans, Ernst; Bachofen, Claudia; Stalder, Hanspeter; Schweizer, Matthias

2010-01-01

Bovine viral diarrhea virus (BVDV), a Flaviviridae pestivirus, is arguably one of the most widespread cattle pathogens worldwide. Each of its two genotypes has two biotypes, non-cytopathic (ncp) and cytopathic (cp). Only the ncp biotype of BVDV may establish persistent infection in the fetus when infecting a dam early in gestation, a time point which predates maturity of the adaptive immune system. Such fetuses may develop and be born healthy but remain infected for life. Due to this early initiation of fetal infection and to the expression of interferon antagonistic proteins, persistently infected (PI) animals remain immunotolerant to the infecting viral strain. Although only accounting for some 1% of all animals in regions where BVDV is endemic, PI animals ensure the viral persistence in the host population. These animals may, however, develop the fatal mucosal disease, which is characterized by widespread lesions in the gastrointestinal tract. Cp BVD virus, in addition to the persisting ncp biotype, can be isolated from such animals. The cp viruses are characterized by unrestrained genome replication, and their emergence from the persisting ncp ones is due to mutations that are unique in each virus analyzed. They include recombinations with host cell mRNA, gene translocations and duplications, and point mutations. Cytopathic BVD viruses fail to establish chains of infection and are unable to cause persistent infection. Hence, these viruses illustrate a case of "viral emergence to extinction" - irrelevant for BVDV evolution, but fatal for the PI host. © INRA, EDP Sciences, 2010.

Long-term decline of the Amazon carbon sink.

Science.gov (United States)

Brienen, R J W; Phillips, O L; Feldpausch, T R; Gloor, E; Baker, T R; Lloyd, J; Lopez-Gonzalez, G; Monteagudo-Mendoza, A; Malhi, Y; Lewis, S L; Vásquez Martinez, R; Alexiades, M; Álvarez Dávila, E; Alvarez-Loayza, P; Andrade, A; Aragão, L E O C; Araujo-Murakami, A; Arets, E J M M; Arroyo, L; Aymard C, G A; Bánki, O S; Baraloto, C; Barroso, J; Bonal, D; Boot, R G A; Camargo, J L C; Castilho, C V; Chama, V; Chao, K J; Chave, J; Comiskey, J A; Cornejo Valverde, F; da Costa, L; de Oliveira, E A; Di Fiore, A; Erwin, T L; Fauset, S; Forsthofer, M; Galbraith, D R; Grahame, E S; Groot, N; Hérault, B; Higuchi, N; Honorio Coronado, E N; Keeling, H; Killeen, T J; Laurance, W F; Laurance, S; Licona, J; Magnussen, W E; Marimon, B S; Marimon-Junior, B H; Mendoza, C; Neill, D A; Nogueira, E M; Núñez, P; Pallqui Camacho, N C; Parada, A; Pardo-Molina, G; Peacock, J; Peña-Claros, M; Pickavance, G C; Pitman, N C A; Poorter, L; Prieto, A; Quesada, C A; Ramírez, F; Ramírez-Angulo, H; Restrepo, Z; Roopsind, A; Rudas, A; Salomão, R P; Schwarz, M; Silva, N; Silva-Espejo, J E; Silveira, M; Stropp, J; Talbot, J; ter Steege, H; Teran-Aguilar, J; Terborgh, J; Thomas-Caesar, R; Toledo, M; Torello-Raventos, M; Umetsu, R K; van der Heijden, G M F; van der Hout, P; Guimarães Vieira, I C; Vieira, S A; Vilanova, E; Vos, V A; Zagt, R J

2015-03-19

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades, with a substantial fraction of this sink probably located in the tropics, particularly in the Amazon. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale, and is contrary to expectations based on models.

Speech Perception and Short-Term Memory Deficits in Persistent Developmental Speech Disorder

Science.gov (United States)

Kenney, Mary Kay; Barac-Cikoja, Dragana; Finnegan, Kimberly; Jeffries, Neal; Ludlow, Christy L.

2006-01-01

Children with developmental speech disorders may have additional deficits in speech perception and/or short-term memory. To determine whether these are only transient developmental delays that can accompany the disorder in childhood or persist as part of the speech disorder, adults with a persistent familial speech disorder were tested on speech…

Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway

Directory of Open Access Journals (Sweden)

Qin Y

2016-12-01

Full Text Available Yue Qin,1,* Suning Li,2,* Gan Zhao,2,* Xuanhao Fu,1 Xueping Xie,1 Yiyi Huang,1 Xiaojing Cheng,3 Jinbin Wei,1 Huagang Liu,1 Zefeng Lai1 1Pharmaceutical College, Guangxi Medical University, 2Department of Pharmacy, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, 3Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of “pristine” or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta and pro-fibrotic growth factors (transforming growth factor-beta 1. Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition

Environmental controls on spatial patterns in the long-term persistence of giant kelp in central California

Science.gov (United States)

Young, Mary Alida; Cavanaugh, Kyle C.; Bell, Tom W.; Raimondi, Peter T.; Edwards, Christopher A.; Drake, Patrick T.; Erikson, Li H.; Storlazzi, Curt

2016-01-01

As marine management is moving towards the practice of protecting static areas, it is 44 important to make sure protected areas capture and protect persistent populations. Rocky reefs in 45 many temperate areas worldwide serve as habitat for canopy forming macroalgae and these 46 structure forming species of kelps (order Laminariales) often serve as important habitat for a great 47 diversity of species. Macrocystis pyrifera is the most common canopy forming kelp species found 48 along the coast of California but the distribution and abundance of M. pyrifera varies in space and 49 time. The purpose of this study is to determine what environmental parameters are correlated with 50 the spatial and temporal persistence of M. pyrifera along the central coast of California and how 51 well those environmental parameters can be used to predict areas where M. pyrifera is more likely 52 to persist. Nine environmental variables considered in this study included depth of the seafloor, 53 structure of the rocky reef, proportion of rocky reef, size of kelp patch, biomass of kelp within a 54 patch, distance from the edge of a kelp patch, sea surface temperature, wave orbital velocities, and 55 population connectivity of individual kelp patches. Using a generalized linear mixed effects model 56 (GLMM), the persistence of M. pyrifera was significantly associated with seven of the nine 57 variables considered: depth, complexity of the rocky reef, proportion of rock, patch biomass, 58 distance from the edge of a patch, population connectivity, and wave-orbital velocities. These 59 seven environmental variables were then used to predict the persistence of kelp across the central 60 coast and these predictions were compared to a reserved dataset of M. pyrifera persistence, which 61 was not used in the creation of the GLMM. The environmental variables were shown to accurately 62 predict the persistence of M. pyrifera within the central coast of California (r = 0.71, P<0.001). 63 Because

Long-term protective immunity from an influenza virus-like particle vaccine administered with a microneedle patch.

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Quan, Fu-Shi; Kim, Yeu-Chun; Song, Jae-Min; Hwang, Hye Suk; Compans, Richard W; Prausnitz, Mark R; Kang, Sang-Moo

2013-09-01

Skin vaccination with influenza virus-like particles (VLPs) using microneedles has been shown to induce protection similar to or better than that induced by intramuscular immunization. In this study, we examined the long-term protective efficacy of influenza (H1N1 A/PR/8/34) VLPs after skin vaccination using microneedle patches coated with the vaccine. Microneedle vaccination of mice in the skin induced 100% protection against lethal challenge infection with influenza A/PR/8/34 virus 14 months after a single vaccine dose. Influenza virus-specific total IgG response and hemagglutination inhibition (HAI) titers were maintained at high levels for over 1 year after microneedle vaccination. Microneedle vaccination also induced substantial levels of lung IgG and IgA antibody responses, and antibody-secreting plasma cells from spleen and bone marrow, as well as conferring effective control of lung viral loads, resulting in complete protection 14 months after vaccination. These strong and long-lasting immune responses were enabled in part by stabilization of the vaccine by formulation with trehalose during microneedle patch fabrication. Administration of the stabilized vaccine using microneedles was especially effective at enabling strong recall responses measured 4 days after lethal virus challenge, including increased HAI and antibody-secreting cells in the spleen and reduced viral titer and inflammatory response in the lung. The results in this study indicate that skin vaccination with VLP vaccine using a microneedle patch provides long-term protection against influenza in mice.

Decreased "ineffective erythropoiesis" preserves polycythemia in mice under long-term hypoxia.

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Harada, Tomonori; Tsuboi, Isao; Hirabayashi, Yukio; Kosaku, Kazuhiro; Naito, Michiko; Hara, Hiroyuki; Inoue, Tohru; Aizawa, Shin

2015-05-01

Hypoxia induces innumerable changes in humans and other animals, including an increase in peripheral red blood cells (polycythemia) caused by the activation of erythropoiesis mediated by increased erythropoietin (EPO) production. However, the elevation of EPO is limited and levels return to normal ranges under normoxia within 5-7 days of exposure to hypoxia, whereas polycythemia continues for as long as hypoxia persists. We investigated erythropoiesis in bone marrow and spleens from mouse models of long-term normobaric hypoxia (10 % O2) to clarify the mechanism of prolonged polycythemia in chronic hypoxia. The numbers of erythroid colony-forming units (CFU-E) in the spleen remarkably increased along with elevated serum EPO levels indicating the activation of erythropoiesis during the first 7 days of hypoxia. After 14 days of hypoxia, the numbers of CFU-E returned to normoxic levels, whereas polycythemia persisted for >140 days. Flow cytometry revealed a prolonged increase in the numbers of TER119-positive cells (erythroid cells derived from pro-erythroblasts through mature erythrocyte stages), especially the TER119 (high) CD71 (high) population, in bone marrow. The numbers of annexin-V-positive cells among the TER119-positive cells particularly declined under chronic hypoxia, suggesting that the numbers of apoptotic cells decrease during erythroid cell maturation. Furthermore, RT-PCR analysis showed that the RNA expression of BMP-4 and stem cell factor that reduces apoptotic changes during erythroid cell proliferation and maturation was increased in bone marrow under hypoxia. These findings indicated that decreased apoptosis of erythroid cells during erythropoiesis contributes to polycythemia in mice during chronic exposure to long-term hypoxia.

Do improvements after inpatient dialectial behavioral therapy persist in the long term? A naturalistic follow-up in patients with borderline personality disorder.

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Kleindienst, Nikolaus; Limberger, Matthias F; Schmahl, Christian; Steil, Regina; Ebner-Priemer, Ulrich W; Bohus, Martin

2008-11-01

Three months of inpatient dialectical behavior therapy proved to be highly effective in patients with borderline personality disorder. This study investigates whether the effects of DBT persist after the patients returned to their usual lives. Thirty-one patients with a diagnosis of borderline personality disorder (DSM-IV) were prospectively followed-up for an observation period of 21 months after discharge from the DBT program, under naturalistic conditions.Improvements as observed after discharge persisted over the full follow-up period. This is reflected in a steady rate of remitted patients and in a broad range of psychopathology showing statistically and clinically significant effect-sizes ranging from 0.70 to 1.71. Analyses of courses over time revealed a high intraindividual concordance, indicating that short term treatment response predicted remission after 2 years follow-up. The effects of inpatient dialectical behavior therapy seem to persist after patients returned to their usual lives.

Long-term exposure to political violence: The particular injury of persistent humiliation.

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Barber, Brian K; McNeely, Clea; Olsen, Joseph A; Belli, Robert F; Doty, Samuel Benjamin

2016-05-01

This study assessed the association between exposure to political violence over a 25-year period and adult functioning among a population that has experienced protracted and severe political conflict. Instead of aggregating exposure to political violence across time and type of exposure, as is commonly done, the event history calendar pioneered in this study assessed exposure to five forms of political violence annually from 1987 to 2011 in a representative sample of 1788 adults, aged 37 on average, in the occupied Palestinian territories (West Bank, East Jerusalem, and the Gaza Strip). This method allowed for the identification of trajectories of exposure to political violence from childhood to adulthood using latent profile analysis. We then correlated the trajectories of exposure to measures of economic, political, community, family, psychological, and health functioning. As expected, being shot at, having one's home raided, being hit or kicked, being verbally abused, and witnessing someone close being humiliated were all elevated during periods of heightened political conflict (the first intifada (1987-1993) and, less so, the second intifada (2000-2005)). In addition, 12% of women and men reported high and persistent levels of exposure to humiliation (being verbally abused and/or witnessing someone close being humiliated) across the entire 25-year period. These individuals lived predominantly in neighborhoods with a high Israeli military presence. Compared to those who experienced periodic exposure to political violence, persistently humiliated men and women reported significantly lower health, economic, political, and psychological functioning, as well as higher social cohesion and political expression. Relevant literatures are reviewed when concluding that persistent humiliation is a neglected form of political violence that is best represented as a direct (versus structural), acute (versus chronic), macro (versus micro), and high-grade (versus low

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

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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

Long-term infection and vertical transmission of a gammaretrovirus in a foreign host species.

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Sakuma, Toshie; Tonne, Jason M; Malcolm, Jessica A; Thatava, Tayaramma; Ohmine, Seiga; Peng, Kah-Whye; Ikeda, Yasuhiro

2012-01-01

Increasing evidence has indicated natural transspecies transmission of gammaretroviruses; however, viral-host interactions after initial xeno-exposure remain poorly understood. Potential association of xenotropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer and chronic fatigue syndrome has attracted broad interests in this topic. Although recent studies have indicated that XMRV is unlikely a human pathogen, further understanding of XMRV xenoinfection would allow in vivo modeling of the initial steps of gammaretroviral interspecies transmission, evolution and dissemination in a new host population. In this study, we monitored the long-term consequences of XMRV infection and its possible vertical transmission in a permissive foreign host, wild-derived Mus pahari mice. One year post-infection, XMRV-infected mice showed no notable pathological changes, while proviral DNA was detected in three out of eight mice. XMRV-infected mice remained seropositive throughout the study although the levels of gp70 Env- and p30 capsid-specific antibodies gradually decreased. When vertical XMRV transmission was assessed, no viremia, humoral immune responses nor endogenization were observed in nine offspring from infected mothers, yet one offspring was found PCR-positive for XMRV-specific sequences. Amplified viral sequences from the offspring showed several mutations, including one amino acid deletion in the receptor binding domain of Env SU. Our results therefore demonstrate long-term asymptomatic infection, low incidence of vertical transmission and limited evolution of XMRV upon transspecies infection of a permissive new host, Mus pahari.

Long-term infection and vertical transmission of a gammaretrovirus in a foreign host species.

Directory of Open Access Journals (Sweden)

Toshie Sakuma

Full Text Available Increasing evidence has indicated natural transspecies transmission of gammaretroviruses; however, viral-host interactions after initial xeno-exposure remain poorly understood. Potential association of xenotropic murine leukemia virus-related virus (XMRV in patients with prostate cancer and chronic fatigue syndrome has attracted broad interests in this topic. Although recent studies have indicated that XMRV is unlikely a human pathogen, further understanding of XMRV xenoinfection would allow in vivo modeling of the initial steps of gammaretroviral interspecies transmission, evolution and dissemination in a new host population. In this study, we monitored the long-term consequences of XMRV infection and its possible vertical transmission in a permissive foreign host, wild-derived Mus pahari mice. One year post-infection, XMRV-infected mice showed no notable pathological changes, while proviral DNA was detected in three out of eight mice. XMRV-infected mice remained seropositive throughout the study although the levels of gp70 Env- and p30 capsid-specific antibodies gradually decreased. When vertical XMRV transmission was assessed, no viremia, humoral immune responses nor endogenization were observed in nine offspring from infected mothers, yet one offspring was found PCR-positive for XMRV-specific sequences. Amplified viral sequences from the offspring showed several mutations, including one amino acid deletion in the receptor binding domain of Env SU. Our results therefore demonstrate long-term asymptomatic infection, low incidence of vertical transmission and limited evolution of XMRV upon transspecies infection of a permissive new host, Mus pahari.

Modeling viral coevolution: HIV multi-clonal persistence and competition dynamics

Science.gov (United States)

Bagnoli, F.; Liò, P.; Sguanci, L.

2006-07-01

The coexistence of different viral strains (quasispecies) within the same host are nowadays observed for a growing number of viruses, most notably HIV, Marburg and Ebola, but the conditions for the formation and survival of new strains have not yet been understood. We present a model of HIV quasispecies competition, which describes the conditions of viral quasispecies coexistence under different immune system conditions. Our model incorporates both T and B cells responses, and we show that the role of B cells is important and additive to that of T cells. Simulations of coinfection (simultaneous infection) and superinfection (delayed secondary infection) scenarios in the early stages (days) and in the late stages of the infection (years) are in agreement with emerging molecular biology findings. The immune response induces a competition among similar phenotypes, leading to differentiation (quasispeciation), escape dynamics and complex oscillations of viral strain abundance. We found that the quasispecies dynamics after superinfection or coinfection has time scales of several months and becomes even slower when the immune system response is weak. Our model represents a general framework to study the speed and distribution of HIV quasispecies during disease progression, vaccination and therapy.

Global synthesis of long-term cloud condensation nuclei observations

Science.gov (United States)

Schmale, Julia; Henning, Silvia; Stratmann, Frank; Henzing, Bas; Schlag, Patrick; Aalto, Pasi; Keskinen, Helmi; Sellegri, Karine; Ovadnevaite, Jurgita; Krüger, Mira; Jefferson, Anne; Whitehead, James; Carslaw, Ken; Yum, Seong Soo; Kristensson, Adam; Baltensperger, Urs; Gysel, Martin

2016-04-01

Cloud condensation nuclei (CCN) are aerosol particles with the ability to activate into droplets at a given super saturation and therefore influence the microphysical and optical properties of clouds. To predict cloud radiative properties understanding the spatial and temporal variability of CCN concentrations in different environments is important. However, currently, the effects of atmospheric particles on changes in cloud radiative forcing are still the largest contribution of uncertainty in climate forcing prediction (IPCC, 2013). Numerous intensive field campaigns have already explored detailed characteristics of CCN in many locations around the world. However, these rather short-term observations can generally not address seasonal or inter-annual variations and a comparison between campaign sites is difficult due to the higher influence of specific environmental circumstances on short-term measurements results. Here, we present results of more long-term CCN and aerosol number concentrations as well as size distribution data covering at least one full year between 2006 and 2014. The 12 locations include ACTRIS stations (http://www.actris.net/) in Europe, and further sites in North America, Brazil and Korea. The sites are located in different environments allowing for temporal and spatial characterization of CCN variability in different atmospheric regimes. Those include marine, remote-continental, boreal forest, rain forest, Arctic and monsoon-influenced environments, as well as boundary layer and free tropospheric conditions. The aerosol populations and their activation behavior show significant differences across the stations. While peak concentrations of CCN are observed in summer at the high altitude sites, in the Arctic the highest concentrations occur during the Haze period in spring. The rural-marine and rural-continental sites exhibit similar CCN concentration characteristics with a relatively flat annual cycle. At some stations, e.g. in the boreal

[Long-term follow-up of patients with suprasellar germinomas].

Science.gov (United States)

Bauditz, Juergen; Lochs, Herbert; Ventz, Manfred

2007-10-15

Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes. The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas. Mean age at diagnosis was 19.7 years (range 15-32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40-54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7-27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case. Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence.

Science.gov (United States)

Sugden, Scott M; Bego, Mariana G; Pham, Tram N Q; Cohen, Éric A

2016-03-03

The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection.

Post-traumatic stress symptoms in long-term non-Hodgkin's lymphoma survivors: does time heal?

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Smith, Sophia K; Zimmerman, Sheryl; Williams, Christianna S; Benecha, Habtamu; Abernethy, Amy P; Mayer, Deborah K; Edwards, Lloyd J; Ganz, Patricia A

2011-12-01

Little is known about the trajectory of post-traumatic stress disorder (PTSD) symptoms in cancer survivors, despite the fact that such knowledge can guide treatment. Therefore, this study examined changes in PTSD symptoms among long-term survivors of non-Hodgkin's lymphoma (NHL) and identified demographic, clinical, and psychosocial predictors and correlates of PTSD symptomatology. Surveys were mailed to 682 NHL survivors who participated in an earlier survey and now were at least 7 years postdiagnosis. Information was obtained regarding PTSD symptoms, positive and negative perceptions of the cancer experience (ie, impact of cancer), and other potential correlates of PTSD. A total of 566 individuals participated (83% response rate) with a median of 12.9 years since diagnosis; respondents were 52% female and 87% white. Although half (51%) of the respondents reported no PTSD symptoms and 12% reported a resolution of symptoms, more than one-third (37%) reported persistence or worsening of symptoms over 5 years. Survivors who reported a low income, stage ≥ 2 at diagnosis, aggressive lymphoma, having received chemotherapy, and greater impact of cancer (both positive and negative) at the initial survey had more PTSD symptoms at follow-up. In multivariable analysis, income and negative impacts of cancer were independent predictors of PTSD symptoms. More than one-third of long-term NHL survivors experience persisting or worsening PTSD symptoms. Providers should be aware of enduring risk; early identification of those at prolonged risk with standardized measures and treatments that target perceptions of the cancer experience might improve long-term outcomes.

Acute Sleep Deprivation Blocks Short- and Long-Term Operant Memory in Aplysia.

Science.gov (United States)

Krishnan, Harini C; Gandour, Catherine E; Ramos, Joshua L; Wrinkle, Mariah C; Sanchez-Pacheco, Joseph J; Lyons, Lisa C

2016-12-01

Insufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk Aplysia californica , a relatively simple model system well known for studies of learning and memory. Aplysia were sleep deprived for 9 hours using context changes and tactile stimulation either prior to or after training for the operant learning paradigm, learning that food is inedible (LFI). The effects of sleep deprivation on short-term (STM) and long-term memory (LTM) were assessed. Acute sleep deprivation prior to LFI training impaired the induction of STM and LTM with persistent effects lasting at least 24 h. Sleep deprivation immediately after training blocked the consolidation of LTM. However, sleep deprivation following the period of molecular consolidation did not affect memory recall. Memory impairments were independent of handling-induced stress, as daytime handled control animals demonstrated no memory deficits. Additional training immediately after sleep deprivation failed to rescue the induction of memory, but additional training alleviated the persistent impairment in memory induction when training occurred 24 h following sleep deprivation. Acute sleep deprivation inhibited the induction and consolidation, but not the recall of memory. These behavioral studies establish Aplysia as an effective model system for studying the interactions between sleep and memory formation. © 2016 Associated Professional Sleep Societies, LLC.

THE ROLE OF EARNINGS PERSISTENCE IN VALUATION ACCURACY AND THE TIME HORIZON

Directory of Open Access Journals (Sweden)

Renê Coppe Pimentel

2016-02-01

Full Text Available Based on the assumption that earnings persistence has implications for both financial analysis and compensation contracts, the aim of this paper is to investigate the role of earnings persistence assuming that (i more persistent earnings are likely to be a better input to valuation models and (ii more persistent earnings are likely to serve as a proxy for long-term market and managerial orientation. The analysis is based on Brazilian listed firms from 1995 to 2013, and while we document strong support for the relevance of earnings persistence in financial analysis and valuation, we fail to document a significant relationship between earnings persistence and long-term value orientation. These results are sensitive to different specifications, and additional results suggest that firms’ idiosyncratic risk (total risk is relevant to explain the focus on short-term outcomes (short-termism across firms. The main contribution of this paper is to offer empirical evidence for the relevance of accounting numbers in both valuation and contractual theories in an emergent market.

Long-term urethral catheterisation.

Science.gov (United States)

Turner, Bruce; Dickens, Nicola

This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

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

PKMζ inhibition prevents the metaplastic change induced by conditioned taste aversion on insular cortex long-term potentiation in vivo.

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Ángeles-Durán, Sandybel; Ramos-Languren, Laura E; Escobar, Martha L

2012-01-01

The activity history of a given neuron or pathway has been suggested to influence its future responses to synaptic inputs. In particular, training in several learning tasks produces a metaplastic change, that is, a change in the ability to induce subsequent synaptic plasticity. Experimental evidence shows that the maintenance of long term memory and long-term potentiation (LTP) requires the persistent action of the atypical protein kinase Cisoform, protein kinase M ζ (PKM ζ ). Recent work has demonstrated that the inactivation of PKM ζ in the insular cortex (IC) abolishes conditioned taste aversion (CTA) long term memory. Our previous studies in the IC have demonstrated that the induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to CTA training enhances the retention of this task. Moreover, recently, we have observed that CTA training blocks the subsequent induction of LTP in the Bla-IC projection. The aim of the present study was to investigate the participation of PKM ζon the CTA-dependent modification of the ability to induce subsequent LTP in the Bla-IC projection in vivo . Thus, we have delivered high-frequency stimulation in the Bla-IC projection in order to induce in vivo IC-LTP in the rats that underwent or did not have an impairment of CTA retention due to the intracortical administration of the selective PKM ζ pseudosubstrate inhibitory peptide, ZIP. Our results show that the microinfusion of ZIP into the IC of the behaving rats impairs long-term memory of CTA and prevents its effects on IC-LTP. These results indicate that PKM ζ is a key component of the cellular mechanisms necessary for the persistence of lasting memory traces as well as for those underlying metaplastic changes in neocortex, contributing to the persistence of aversive memories.

Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies.

Science.gov (United States)

Lee, Hye-Ra; Choi, Un Yung; Hwang, Sung-Woo; Kim, Stephanie; Jung, Jae U

2016-11-30

The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit. In particular, due to the potent antiviral activities of IFN and cytokines, viruses have developed various strategies to meticulously modulate intracellular innate immune sensing mechanisms to facilitate efficient viral replication and persistence. In this review, we highlight recent advances in the study of viral immune evasion strategies with a specific focus on how Kaposi's sarcoma-associated herpesvirus (KSHV) effectively targets host PRR signaling pathways.

Long-term persistence of acquired resistance to 5-fluorouracil in the colon cancer cell line SW620

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Tentes, I.K., E-mail: itentes@med.duth.gr [Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece); Schmidt, W.M. [Center for Anatomy and Cell Biology, Waehringer Strasse 13, 1090 Vienna (Austria); Krupitza, G. [Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Steger, G.G.; Mikulits, W. [Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Kortsaris, A. [Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece); Mader, R.M. [Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

2010-11-15

Treatment resistance to antineoplastic drugs represents a major clinical problem. Here, we investigated the long-term stability of acquired resistance to 5-fluorouracil (FU) in an in vitro colon cancer model, using four sub-clones characterised by increasing FU-resistance derived from the cell line SW620. The resistance phenotype was preserved after FU withdrawal for 15 weeks ({approx} 100 cell divisions) independent of the established level of drug resistance and of epigenetic silencing. Remarkably, resistant clones tolerated serum deprivation, adopted a CD133{sup +} CD44{sup -} phenotype, and further exhibited loss of membrane-bound E-cadherin together with predominant nuclear {beta}-catenin localisation. Thus, we provide evidence for a long-term memory of acquired drug resistance, driven by multiple cellular strategies (epithelial-mesenchymal transition and selective propagation of CD133{sup +} cells). These resistance phenomena, in turn, accentuate the malignant phenotype.

Long-term follow-up after mesh removal and selective neurectomy for persistent inguinal postherniorrhaphy pain

DEFF Research Database (Denmark)

Bischoff, J M; Enghuus, Casper Nørskov; Werner, M U

2013-01-01

PURPOSE: Persistent inguinal pain, influencing daily activities, is seen in about 5 % of patients following inguinal herniorrhaphy. Surgical treatment of patients with persistent postherniorrhaphy pain has been associated with pain relief and improvement in functional status. However, the detailed...... and functional ability when comparing preoperative and postoperative assessments. RESULTS: Pain intensities (average, maximum, and during activity) were significantly lower at all time points during follow-up compared to preoperative values (p ...

[Long term persistence of yellow fever neutralising antibodies in elderly persons].

Science.gov (United States)

Coulange Bodilis, H; Benabdelmoumen, G; Gergely, A; Goujon, C; Pelicot, M; Poujol, P; Consigny, P H

2011-10-01

The activity of the yellow fever virus is reemerging in areas without recent transmission history, such as northern Argentina and Paraguay, and persists in an epidemic mode in other countries in Africa and Latin America. Thus more and more travelers are at risk of being exposed to this disease. The population is becoming older, sometimes suffering from multiple pathologies. Moreover, the risk of serious adverse events associated with live-attenuated YF17D vaccine, such as multiple organ failure (YEL-AVD), reaches 1/50,000 vaccines in people over 65 versus 1/200,000 in the general population. We analyzed, in a retrospective study, the results of neutralizing antibody titers against yellow fever in people aged 60 and older, who had been previously vaccinated against yellow fever and had visited the International Vaccination Centre of the Institut Pasteur between January 2005 and February 2009. In this population of 84 persons (median age 69 years), the date of the last vaccination was always more than 10 years: it was precisely known in 68 subjects and alleged in 16 subjects. The median time since the previous vaccination was 14 years, with a maximum of 60 years. The indications of serology were: immunosuppressive therapy (19% of cases), cancer (32%), hemopathy (10.7%), HIV infection (3.6%), chronic hepatitis/chronic renal failure/dialysis (2.4%), autoimmune diseases (2.4%), and in 29.8% of cases, age alone was the indication of serology. The antibody titer was at a protective level in 95.2% of cases. The four individuals with negative serology had no formal documented proof of a previous vaccination against yellow fever. This serological study was able to show a persistent protective antibody titer, after a previous vaccination, even going back 60 years, allowing patients to travel in a yellow-fever endemic area despite a contraindication, and without requiring any vaccine booster.

Predictors of Long-Term Healthy Arterial Aging: Coronary Artery Calcium Nondevelopment in the MESA Study.

Science.gov (United States)

Whelton, Seamus P; Silverman, Michael G; McEvoy, John W; Budoff, Matthew J; Blankstein, Ron; Eng, John; Blumenthal, Roger S; Szklo, Moyses; Nasir, Khurram; Blaha, Michael J

2015-12-01

This study sought to determine the predictors of healthy arterial aging. Long-term nondevelopment of coronary artery calcification (persistent CAC = 0) is a marker of healthy arterial aging. The predictors of this phenotype are not known. We analyzed 1,850 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 who underwent a follow-up CAC scan at visit 5 (median 9.6 years after baseline). We examined the proportion with persistent CAC = 0 and calculated multivariable relative risks and area under the receiver operating characteristic curve for prediction of this healthy arterial aging phenotype. We found that 55% of participants (n = 1,000) had persistent CAC = 0, and these individuals were significantly more likely to be younger, female, and have fewer traditional risk factors (RF). Participants with an ASCVD (Atherosclerotic Cardiovascular Disease Risk Score) risk score healthy arterial aging than were participants with an ASCVD score ≥7.5%. There was no significant association between the Healthy Lifestyle variables (body mass index, physical activity, Mediterranean diet, and never smoking) and persistent CAC = 0. The area under the receiver operating characteristic curve incorporating age, sex, and ethnicity was 0.65, indicating fair to poor discrimination. No single traditional RF or combination of other risk factors increased the area under the receiver operating characteristic curve by more than 0.05. Whereas participants free of traditional cardiovascular disease RF were significantly more likely to have persistent CAC = 0, there was no single RF or specific low-risk RF phenotype that markedly improved the discrimination of persistent CAC = 0 over demographic variables. Therefore, we conclude that healthy arterial aging may be predominantly influenced by the long-term maintenance of a low cardiovascular disease risk profile or yet to be determined genetic factors rather than the absence of any specific RF cluster identified

Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

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Eric J. Neuberger

2017-09-01

Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

Long-term associative learning predicts verbal short-term memory performance.

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Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

The persistence of marketing effects on sales

OpenAIRE

Dekimpe, Marnik; Hanssens, DM

1993-01-01

Are marketing efforts able to affect long-term trends in sales or other performance measures? Answering this question is essential for the creation of marketing strategies that deliver a sustainable competitive advantage. This paper introduces persistence modeling to derive long-term marketing effectiveness from time-series observations on sales and marketing expenditures. First, we use unit-root tests to determine whether sales are stable or evolving (trending) over time. If they are evolvin...

A trade-off between natural and acquired antibody production in a reptile: implications for long-term resistance to disease

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Franziska C. Sandmeier

2012-08-01

Vertebrate immune systems are understood to be complex and dynamic, with trade-offs among different physiological components (e.g., innate and adaptive immunity within individuals and among taxonomic lineages. Desert tortoises (Gopherus agassizii immunised with ovalbumin (OVA showed a clear trade-off between levels of natural antibodies (NAbs; innate immune function and the production of acquired antibodies (adaptive immune function. Once initiated, acquired antibody responses included a long-term elevation in antibodies persisting for more than one year. The occurrence of either (a high levels of NAbs or (b long-term elevations of acquired antibodies in individual tortoises suggests that long-term humoral resistance to pathogens may be especially important in this species, as well as in other vertebrates with slow metabolic rates, concomitantly slow primary adaptive immune responses, and long life-spans.

A Protein Synthesis and Nitric Oxide-Dependent Presynaptic Enhancement in Persistent Forms of Long-Term Potentiation

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Johnstone, Victoria P. A.; Raymond, Clarke R.

2011-01-01

Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre- and post-synaptic expression mechanisms in LTP1, 2,…

Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders.

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Nicola Lehners

Full Text Available Respiratory viruses are a cause of upper respiratory tract infections (URTI, but can be associated with severe lower respiratory tract infections (LRTI in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17% were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111 underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic. LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1pdm09, A(H3N2, influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75% of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01 and was most pronounced in patients with RSV infection (n = 16 with a median duration of viral shedding for 80 days (range 35-334 days. Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for

Persistent infection caused by Hobi-like pestivirus.

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Decaro, Nicola; Losurdo, Michele; Lucente, Maria Stella; Sciarretta, Rossana; Mari, Viviana; Larocca, Vittorio; Elia, Gabriella; Cavaliere, Nicola; Martella, Vito; Fasanella, Antonio; Buonavoglia, Canio

2013-04-01

A calf persistently infected by Hobi-like pestivirus was monitored for about 6 months, displaying clinical signs typical of bovine viral diarrhea virus persistent infection and shedding the virus through all body secretions, with maximal titers detected in urine. This report provides new insights into the pathogenesis of the emerging pestivirus.

Web-based Distributed Medical Information System for Chronic Viral Hepatitis

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Yang, Ying; Qin, Tuan-fa; Jiang, Jian-ning; Lu, Hui; Ma, Zong-e.; Meng, Hong-chang

2008-11-01

To make a long-term dynamic monitoring to the chronically ill, especially patients of HBV A, we build a distributed Medical Information System for Chronic Viral Hepatitis (MISCHV). The Web-based system architecture and its function are described, and the extensive application and important role are also presented.

Long-term stability of intracortical recordings using perforated and arrayed Parylene sheath electrodes

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Hara, Seth A.; Kim, Brian J.; Kuo, Jonathan T. W.; Lee, Curtis D.; Meng, Ellis; Pikov, Victor

2016-12-01

Objective. Acquisition of reliable and robust neural recordings with intracortical neural probes is a persistent challenge in the field of neuroprosthetics. We developed a multielectrode array technology to address chronic intracortical recording reliability and present in vivo recording results. Approach. The 2 × 2 Parylene sheath electrode array (PSEA) was microfabricated and constructed from only Parylene C and platinum. The probe includes a novel three-dimensional sheath structure, perforations, and bioactive coatings that improve tissue integration and manage immune response. Coatings were applied using a sequential dip-coating method that provided coverage over the entire probe surface and interior of the sheath structure. A sharp probe tip taper facilitated insertion with minimal trauma. Fabricated probes were subject to examination by optical and electron microscopy and electrochemical testing prior to implantation. Main results. 1 × 2 arrays were successfully fabricated on wafer and then packaged together to produce 2 × 2 arrays. Then, probes having electrode sites with adequate electrochemical properties were selected. A subset of arrays was treated with bioactive coatings to encourage neuronal growth and suppress inflammation and another subset of arrays was implanted in conjunction with a virally mediated expression of Caveolin-1. Arrays were attached to a custom-made insertion shuttle to facilitate precise insertion into the rat motor cortex. Stable electrophysiological recordings were obtained during the period of implantation up to 12 months. Immunohistochemical evaluation of cortical tissue around individual probes indicated a strong correlation between the electrophysiological performance of the probes and histologically observable proximity of neurons and dendritic sprouting. Significance. The PSEA demonstrates the scalability of sheath electrode technology and provides higher electrode count and density to access a greater volume for recording

HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation

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McQuown, Susan C.; Barrett, Ruth M.; Matheos, Dina P.; Post, Rebecca J.; Rogge, George A.; Alenghat, Theresa; Mullican, Shannon E.; Jones, Steven; Rusche, James R.; Lazar, Mitchell A.; Wood, Marcelo A.

2011-01-01

Gene expression is dynamically regulated by chromatin modifications on histone tails, such as acetylation. In general, histone acetylation promotes transcription, whereas histone deacetylation negatively regulates transcription. The interplay between histone acetyl-transerases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes. Currently, very little is known about the role of individual HDACs in learning and memory. We examined the role of HDAC3 in long-term memory using a combined genetic and pharmacologic approach. We used HDAC3–FLOX genetically modified mice in combination with adeno-associated virus-expressing Cre recombinase to generate focal homozygous deletions of Hdac3 in area CA1 of the dorsal hippocampus. To complement this approach, we also used a selective inhibitor of HDAC3, RGFP136 [N-(6-(2-amino-4-fluorophenylamino)-6-oxohexyl)-4-methylbenzamide]. Immunohistochemistry showed that focal deletion or intrahippocampal delivery of RGFP136 resulted in increased histone acetylation. Both the focal deletion of HDAC3 as well as HDAC3 inhibition via RGFP136 significantly enhanced long-term memory in a persistent manner. Next we examined expression of genes implicated in long-term memory from dorsal hippocampal punches using quantitative reverse transcription-PCR. Expression of nuclear receptor subfamily 4 group A, member 2 (Nr4a2) and c-fos was significantly increased in the hippocampus of HDAC3–FLOX mice compared with wild-type controls. Memory enhancements observed in HDAC3–FLOX mice were abolished by intrahippocampal delivery of Nr4a2 small interfering RNA, suggesting a mechanism by which HDAC3 negatively regulates memory formation. Together, these findings demonstrate a critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation. PMID:21228185

Distribution of bovine viral diarrhoea virus antigen in persistently infected white-tailed deer (Odocoileus virginianus).

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Passler, T; Walz, H L; Ditchkoff, S S; van Santen, E; Brock, K V; Walz, P H

2012-11-01

Infection with bovine viral diarrhoea virus (BVDV), analogous to that occurring in cattle, is reported rarely in white-tailed deer (Odocoileus virginianus). This study evaluated the distribution of BVDV antigen in persistently infected (PI) white-tailed deer and compared the findings with those from PI cattle. Six PI fawns (four live-born and two stillborn) from does exposed experimentally to either BVDV-1 or BVDV-2 were evaluated. Distribution and intensity of antigen expression in tissues was evaluated by immunohistochemistry. Data were analyzed in binary fashion with a proportional odds model. Viral antigen was distributed widely and was present in all 11 organ systems. Hepatobiliary, integumentary and reproductive systems were respectively 11.8, 15.4 and 21.6 times more likely to have higher antigen scores than the musculoskeletal system. Pronounced labelling occurred in epithelial tissues, which were 1.9-3.0 times likelier than other tissues to contain BVDV antigen. Antigen was present in >90% of samples of liver and skin, suggesting that skin biopsy samples are appropriate for BVDV diagnosis. Moderate to severe lymphoid depletion was detected and may hamper reliable detection of BVDV in lymphoid organs. Muscle tissue contained little antigen, except for in the cardiovascular system. Antigen was present infrequently in connective tissues. In nervous tissues, antigen expression frequency was 0.3-0.67. In the central nervous system (CNS), antigen was present in neurons and non-neuronal cells, including microglia, emphasizing that the CNS is a primary target for fetal BVDV infection. BVDV antigen distribution in PI white-tailed deer is similar to that in PI cattle. Copyright © 2012 Elsevier Ltd. All rights reserved.

Long-term results of symptomatic fibroids treated with uterine artery embolization: In conjunction with MR evaluation

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Kim, Man Deuk [Department of Diagnostic Radiology Bundang CHA General Hospital, Pochon CHA University (Korea, Republic of)], E-mail: mdkim@cha.ac.kr; Lee, Hyun Seok [Department of Diagnostic Radiology Bundang CHA General Hospital, Pochon CHA University (Korea, Republic of); Lee, Mee Hwa [Department of Obstetrics and Gynecology, Bundang CHA General Hospital, Pochon CHA University (Korea, Republic of); Kim, Hee Jin [Department of Diagnostic Radiology Bundang CHA General Hospital, Pochon CHA University (Korea, Republic of); Cho, Jin Ho; Cha, Sun Hee [Department of Obstetrics and Gynecology, Bundang CHA General Hospital, Pochon CHA University (Korea, Republic of)

2010-02-15

Objective: The aim of the present study is to determine long-term clinical efficacy of uterine fibroid embolization (UFE) for symptomatic fibroids in conjunction with MR evaluation. Materials and methods: Sixteen patients with a follow-up period of 4 years or longer were analyzed retrospectively. Ages ranged from 27 to 45 (mean 39.5) years. Mean follow-up periods were 5.8 years (range: 4.1-6.9 years). The symptom changes, in terms of menorrhagia and dysmenorrhea and bulk-related symptoms, were assessed. The primary embolic agent was polyvinyl alcohol particle (250-710 {mu}m). All patients underwent preprocedural and long-term follow up MR imaging. Uterine volumes were calculated using MRI. Results: Symptom improvements were reported for menorrhagia (8/9, 88.9%), dysmenorrhea (5/5, 100%), and bulk-related symptoms (7/9, 77.8%) at long-term follow up. Two patients (12.5%) had symptom recurrences at long-term follow-up. Tumor regrowth from incomplete infarction was a cause of recurrence in one patient and newly developed leiomyomas in the other one. One patient underwent hysterectomy because endometriosis developed 4 years after UFE. Of the 14 necrotic myomas on short-term follow up MR after UFE, eight (57.1%) demonstrated maintaining necrosis with further shrinkage and six (42.9%) were no longer visualized on long-term follow up MR images. Overall, the mean volume reduction rates of the predominant fibroid and uterus were 80.5%, 36.7% at long-term follow up, respectively. Conclusion: UFE is an effective treatment for symptomatic fibroids with an acceptable long-term success rate. Long-term MR imaging after UFE revealed persistent necrotic fibroid, non-visualization of fibroids and tumor regrowth when incompletely infarcted.

Long-term results of symptomatic fibroids treated with uterine artery embolization: In conjunction with MR evaluation

International Nuclear Information System (INIS)

Kim, Man Deuk; Lee, Hyun Seok; Lee, Mee Hwa; Kim, Hee Jin; Cho, Jin Ho; Cha, Sun Hee

2010-01-01

Objective: The aim of the present study is to determine long-term clinical efficacy of uterine fibroid embolization (UFE) for symptomatic fibroids in conjunction with MR evaluation. Materials and methods: Sixteen patients with a follow-up period of 4 years or longer were analyzed retrospectively. Ages ranged from 27 to 45 (mean 39.5) years. Mean follow-up periods were 5.8 years (range: 4.1-6.9 years). The symptom changes, in terms of menorrhagia and dysmenorrhea and bulk-related symptoms, were assessed. The primary embolic agent was polyvinyl alcohol particle (250-710 μm). All patients underwent preprocedural and long-term follow up MR imaging. Uterine volumes were calculated using MRI. Results: Symptom improvements were reported for menorrhagia (8/9, 88.9%), dysmenorrhea (5/5, 100%), and bulk-related symptoms (7/9, 77.8%) at long-term follow up. Two patients (12.5%) had symptom recurrences at long-term follow-up. Tumor regrowth from incomplete infarction was a cause of recurrence in one patient and newly developed leiomyomas in the other one. One patient underwent hysterectomy because endometriosis developed 4 years after UFE. Of the 14 necrotic myomas on short-term follow up MR after UFE, eight (57.1%) demonstrated maintaining necrosis with further shrinkage and six (42.9%) were no longer visualized on long-term follow up MR images. Overall, the mean volume reduction rates of the predominant fibroid and uterus were 80.5%, 36.7% at long-term follow up, respectively. Conclusion: UFE is an effective treatment for symptomatic fibroids with an acceptable long-term success rate. Long-term MR imaging after UFE revealed persistent necrotic fibroid, non-visualization of fibroids and tumor regrowth when incompletely infarcted.

Transforming Growth Factor ß Recruits Persistent MAPK Signaling to Regulate Long-Term Memory Consolidation in "Aplysia Californica"

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Shobe, Justin; Philips, Gary T.; Carew, Thomas J.

2016-01-01

In this study, we explore the mechanistic relationship between growth factor signaling and kinase activity that supports the protein synthesis-dependent phase of long-term memory (LTM) consolidation for sensitization of "Aplysia." Specifically, we examine LTM for tail shock-induced sensitization of the tail-elicited siphon withdrawal…

PKMzeta maintains 1-day- and 6-day-old long-term object location but not object identity memory in dorsal hippocampus.

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Hardt, Oliver; Migues, Paola V; Hastings, Margaret; Wong, Jacinda; Nader, Karim

2010-06-01

Continuous activity of the atypical protein kinase C isoform M zeta (PKMzeta) is necessary for maintaining long-term memory acquired in aversively or appetitively motivated associative learning tasks, such as active avoidance, aversive taste conditioning, auditory and contextual fear conditioning, radial arm maze, and watermaze. Whether unreinforced, nonassociative memory will also require PKMzeta for long-term maintenance is not known. Using recognition memory for object location and object identity, we found that inactivating PKMzeta in dorsal hippocampus abolishes 1-day and 6-day-old long-term recognition memory for object location, while recognition memory for object identity was not affected by this treatment. Memory for object location persisted for no more than 35 days after training. These results suggest that the dorsal hippocampus mediates long-term memory for where, but not what things have been encountered, and that PKMzeta maintains this type of spatial knowledge as long as the memory exists.

Significance of actinide chemistry for the long-term safety of waste disposal

International Nuclear Information System (INIS)

Kim, Jae Il

2006-01-01

A geochemical approach to the long-term safety of waste disposal is discussed in connection with the significance of actinides, which shall deliver the major radioactivity inventory subsequent to the relatively short-term decay of fission products. Every power reactor generates transuranic (TRU) elements: plutonium and minor actinides (Np, Am, Cm), which consist chiefly of long-lived nuclides emitting alpha radiation. The amount of TRU actinides generated in a fuel life period is found to be relatively small (about 1 wt% or less in spent fuel) but their radioactivity persists many hundred thousands years. Geological confinement of waste containing TRU actinides demands, as a result, fundamental knowledge on the geochemical behavior of actinides in the repository environment for a long period of time. Appraisal of the scientific progress in this subject area is the main objective of the present paper. Following the introductory discussion on natural radioactivities, the nuclear fuel cycle is briefly brought up with reference to actinide generation and waste disposal. As the long-term disposal safety concerns inevitably with actinides, the significance of the aquatic actinide chemistry is summarized in two parts: the fundamental properties relevant to their aquatic behavior and the geochemical reactions in nanoscopic scale. The constrained space of writing allows discussion on some examples only, for which topics of the primary concern are selected, e.g. apparent solubility and colloid generation, colloid-facilitated migration, notable speciation of such processes, etc. Discussion is summed up to end with how to make a geochemical approach available for the long-term disposal safety of nuclear waste or for the Performance Assessment (PA) as known generally

Effects of interferon-tau on cattle persistently infected with bovine viral diarrhea virus.

Science.gov (United States)

Kohara, Junko; Nishikura, Yumiko; Konnai, Satoru; Tajima, Motoshi; Onuma, Misao

2012-08-01

In this study, the antiviral effects of bovine interferon-tau (boIFN-tau) on bovine viral diarrhea virus (BVDV) were examined in vitro and in vivo. In the in vitro experiments, the replication of cytopathic and non-cytopathic BVDV was inhibited in the bovine cells treated with boIFN-tau. The replication of BVDV was completely suppressed by boIFN-tau at a concentration higher than 10(2) U/ml. In order to examine the effect of boIFN-tau on virus propagation in cattle persistently infected (PI) with non-cytopathic BVDV, boIFN-tau was subcutaneously administered to PI cattle at 10(5) U/kg or 10(6) U/kg body weight 5 times per week for 2 weeks. No physical abnormality such as depression was observed in the cattle during the experiment. The mean BVDV titers in the serum of the PI cattle decreased slightly during the boIFN-tau administration period with the dose of 10(6) U/kg. However, the BVDV titers in the serum returned to the pre-administration level after the final boIFN-tau administration. These results suggest that boIFN-tau demonstrates an anti-BVDV effect, reducing the BVDV level in serum transiently when injected into PI cattle.

Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory.

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Havekes, Robbert; Park, Alan J; Tolentino, Rosa E; Bruinenberg, Vibeke M; Tudor, Jennifer C; Lee, Yool; Hansen, Rolf T; Guercio, Leonardo A; Linton, Edward; Neves-Zaph, Susana R; Meerlo, Peter; Baillie, George S; Houslay, Miles D; Abel, Ted

2016-08-24

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular compartments. The

Late protein synthesis-dependent phases in CTA long-term memory: BDNF requirement

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Araceli eMartínez-Moreno

2011-09-01

Full Text Available It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memory when protein synthesis was inhibited. Our previous studies on the insular cortex (IC, a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA, have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis dependent in different time-windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 hours after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.

Long-term effects of islet transplantation.

Science.gov (United States)

Holmes-Walker, D Jane; Kay, Thomas W H

2016-10-01

Islet transplantation has made great progress in recent years. This is a remarkable technical feat but raises the question of what the long-term benefits and risks are for type I diabetes recipients. Graft survival continues to improve, and recent multicenter studies show that islet transplantation is particularly effective to prevent hypoglycemic events even in those who do not become insulin-independent and to achieve excellent glycemic control. Concerns include histocompatability leucocyte antigen (HLA) sensitization and other risks including from immunosuppression that islet transplantation shares with other forms of allotransplantation. Reversal of hypoglycemia unawareness and protection from severe hypoglycemia events are two of the main benefits of islet transplantation and they persist for the duration of graft function. Islet transplantation compares favorably with other therapies for those with hypoglycemia unawareness, although new technologies have not been tested head-to-head with transplantation. HLA sensitization increases with time after transplantation especially if immunosuppression is ceased and is a risk for those who may require future transplantation as well as being associated with loss of graft function.

Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

Science.gov (United States)

Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

2012-01-01

Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

Primary sleep disorders can cause long-term sleep disturbance in patients with autoimmune mediated limbic encephalitis.

Science.gov (United States)

Anderson, Kirstie N; Kelly, Thomas P; Griffiths, Timothy D

2013-07-01

Antibody mediated limbic encephalitis causes a sub acute encephalopathy with an amnestic syndrome, seizures and often an affective prodrome. Sleep disturbance including abnormal dream sleep and insomnia are described in a percentage of long-term survivors but there are very few detailed assessments of sleep disturbance in patients beyond the acute phase of illness. The objectives of this study were to understand the causes of sleep disturbance in the long-term survivors of antibody mediated limbic encephalitis. We screened twelve patients under long-term follow up with sleep questionnaires and went on to perform detailed sleep studies (polysomnography) in those who reported sleep disturbance. Two were found to have persistent, severe central and obstructive sleep apnoea and two others to have restless legs and periodic limb movements of sleep. This highlights the need to investigate sleep disturbance in this group of patients. Effective treatments may be available to improve quality of life and daytime function. Copyright © 2012 Elsevier B.V. All rights reserved.

An Epstein-Barr virus encoded inhibitor of Colony Stimulating Factor-1 signaling is an important determinant for acute and persistent EBV infection.

Directory of Open Access Journals (Sweden)

Makoto Ohashi

2012-12-01

Full Text Available Acute Epstein-Barr virus (EBV infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1 signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV, naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1. Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection.

Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.

Science.gov (United States)

Dossat, Amanda M; Jourdi, Hussam; Wright, Katherine N; Strong, Caroline E; Sarkar, Ambalika; Kabbaj, Mohamed

2017-01-06

In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Reforming Long-Term Care Funding in Alberta.

Science.gov (United States)

Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

2015-01-01

Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

Viral Evasion of Natural Killer Cell Activation

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Yi Ma

2016-04-01

Full Text Available Natural killer (NK cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

Viral Evasion of Natural Killer Cell Activation.

Science.gov (United States)

Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

2016-04-12

Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

DEFF Research Database (Denmark)

Engsig, Frederik N; Zangerle, Robert; Katsarou, Olga

2014-01-01

BACKGROUND: Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years...... of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing...... age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3...

pEPito: a significantly improved non-viral episomal expression vector for mammalian cells

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Ogris Manfred

2010-03-01

Full Text Available Abstract Background The episomal replication of the prototype vector pEPI-1 depends on a transcription unit starting from the constitutively expressed Cytomegalovirus immediate early promoter (CMV-IEP and directed into a 2000 bp long matrix attachment region sequence (MARS derived from the human β-interferon gene. The original pEPI-1 vector contains two mammalian transcription units and a total of 305 CpG islands, which are located predominantly within the vector elements necessary for bacterial propagation and known to be counterproductive for persistent long-term transgene expression. Results Here, we report the development of a novel vector pEPito, which is derived from the pEPI-1 plasmid replicon but has considerably improved efficacy both in vitro and in vivo. The pEPito vector is significantly reduced in size, contains only one transcription unit and 60% less CpG motives in comparison to pEPI-1. It exhibits major advantages compared to the original pEPI-1 plasmid, including higher transgene expression levels and increased colony-forming efficiencies in vitro, as well as more persistent transgene expression profiles in vivo. The performance of pEPito-based vectors was further improved by replacing the CMV-IEP with the human CMV enhancer/human elongation factor 1 alpha promoter (hCMV/EF1P element that is known to be less affected by epigenetic silencing events. Conclusions The novel vector pEPito can be considered suitable as an improved vector for biotechnological applications in vitro and for non-viral gene delivery in vivo.

Heavy Alcohol Consumption Effects on Blood Pressure and on Kidney Structure Persist After Long-Term Withdrawal

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Sandra Leal

2017-11-01

Full Text Available Background/Aims: Heavy ethanol consumption is a risk factor for hypertension and prompts organ damage. There is no information regarding the impact of long-term heavy ethanol consumption on kidney structure and function linking to their hypertensive effects nor the repercussions after withdrawal. Methods: Rats were exposed to ethanol for 24 weeks and, afterwards, a group was assigned to withdrawal for 8 weeks. Blood pressure (BP was measured and serum biochemical parameters were quantified. Glomerular volume density, areal density of glomerular tuft and renal corpuscles were determined. Angiotensin II type 1 receptor (AT1R protein expression was evaluated. Results: Twenty-four weeks of ethanol consumption causes atrophy of renal corpuscles and glomeruli and reduces the volume of glomeruli. Glomerular changes induced by ethanol consumption were still evident after withdrawal. Renal AT1R levels were increased in ethanol-treated rats and returned to control levels during withdrawal. Ethanol consumption also induced an increase in BP, uric acid and albumin levels. Upon withdrawal, systolic and mean arterial pressures decreased, but were still higher than in controls rats. Conclusion: Ethanol consumption induces changes in glomerular morphology associated with increased BP and AT1R expression. Long-term withdrawal was inefficient to restore the structural integrity of renal corpuscles and in lowering systolic pressure.

Industrial Foundations as Long-Term Owners

DEFF Research Database (Denmark)

Thomsen, Steen; Poulsen, Thomas; Børsting, Christa Winther

Short-termism has become a serious concern for corporate governance, and this has inspired a search for institutional arrangements to promote long-term decision-making. In this paper, we call attention to long-term ownership by industrial foundations, which is common in Northern Europe but little...... known in the rest of the world. We use a unique Danish data set to document that industrial foundations are long-term owners that practice long-term governance. We show that foundation ownership is highly stable compared to other ownership structures. Foundation-owned companies replace managers less...... frequently. They have conservative capital structures with low financial leverage. They score higher on an index of long-termism in finance, investment, and employment. They survive longer. Overall, our paper supports the hypothesis that corporate time horizons are influenced by ownership structures...

Long-term associative learning predicts verbal short-term memory performance

OpenAIRE

Jones, Gary; Macken, Bill

2017-01-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term...

Long-term outcome in dogs with patent ductus arteriosus: 520 cases (1994-2009).

Science.gov (United States)

Saunders, A B; Gordon, S G; Boggess, M M; Miller, M W

2014-01-01

Published information regarding survival and long-term cardiac remodeling after patent ductus arteriosus (PDA) closure in dogs is limited. To report outcome and identify prognostic variables in dogs with PDA, and to identify risk factors for persistent remodeling in dogs with a minimum of 12 months of follow-up after closure. Five hundred and twenty client-owned dogs. Retrospective review of medical records of 520 dogs with PDA. Outcome was determined by contacting owners and veterinarians. Dogs with PDA closure and ≥ 12 months of follow-up were asked to return for a re-evaluation. In multivariable analysis of 506 dogs not euthanized at the time of diagnosis, not having a PDA closure procedure negatively affected survival (HzR = 16.9, P closure, clinical signs at presentation (HzR = 17, P = .02), concurrent congenital heart disease (HD) (HzR = 4.8, P = .038), and severe mitral regurgitation (MR) documented within 24 hours of closure (HzR = 4.5, P = .028) negatively affected survival. Seventy-one dogs with ≥ 12 months follow-up demonstrated a significant reduction in radiographic and echocardiographic measures of heart size (P = 0) and increased incidence of acquired HD (P = .001) at re-evaluation. Dogs with increased left ventricular size and low fractional shortening at baseline were more likely to have persistent remodeling at re-evaluation. Patent ductus arteriosus closure confers important survival benefits and results in long-term reverse remodeling in most dogs. Clinical signs at presentation, concurrent congenital HD, and severe MR negatively affect survival. Increased left ventricular systolic dimensions and systolic dysfunction at baseline correlated significantly with persistent remodeling. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Understanding the Innate Immune Response in Viral Hepatitis : Interferons and NK Cells

NARCIS (Netherlands)

R.A. de Groen (Rik)

2017-01-01

textabstractHBV and HCV infection are the two leading causes of chronic liver inflammation worldwide, affecting an approximate 370–390 million people. Currently, the viral and immunological mechanisms that underlie either the resolution or persistence of viral hepatitis infections are not fully

The clinical utility of long-term humidification therapy in chronic airway disease.

Science.gov (United States)

Rea, Harold; McAuley, Sue; Jayaram, Lata; Garrett, Jeffrey; Hockey, Hans; Storey, Louanne; O'Donnell, Glenis; Haru, Lynne; Payton, Matthew; O'Donnell, Kevin

2010-04-01

Persistent airway inflammation with mucus retention in patients with chronic airway disorders such as COPD and bronchiectasis may lead to frequent exacerbations, reduced lung function and poor quality of life. This study investigates if long-term humidification therapy with high flow fully humidified air at 37 degrees C through nasal cannulae can improve these clinical outcomes in this group of patients. 108 patients diagnosed with COPD or bronchiectasis were randomised to daily humidification therapy or usual care for 12 months over which exacerbations were recorded. Lung function, quality of life, exercise capacity, and measures of airway inflammation were also recorded at baseline, 3 and 12 months. Patients on long-term humidification therapy had significantly fewer exacerbation days (18.2 versus 33.5 days; p = 0.045), increased time to first exacerbation (median 52 versus 27 days; p = 0.0495) and reduced exacerbation frequency (2.97/patient/year versus 3.63/patient/year; p = 0.067) compared with usual care. Quality of life scores and lung function improved significantly with humidification therapy compared with usual care at 3 and 12 months. Long-term humidification therapy significantly reduced exacerbation days, increased time to first exacerbation, improved lung function and quality of life in patients with COPD and bronchiectasis. Clinical trial registered with www.actr.org.au; Number ACTRN2605000623695. Copyright 2010 Elsevier Ltd. All rights reserved.

Autophagy pathway induced by a plant virus facilitates viral spread and transmission by its insect vector.

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Yong Chen

2017-11-01

Full Text Available Many viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems. Generally, an insect vector can use autophagy as an intrinsic antiviral defense mechanism against viral infection. Whether viruses can evolve to exploit autophagy to promote their transmission by insect vectors is still unknown. Here, we show that the autophagic process is triggered by the persistent replication of a plant reovirus, rice gall dwarf virus (RGDV in cultured leafhopper vector cells and in intact insects, as demonstrated by the appearance of obvious virus-containing double-membrane autophagosomes, conversion of ATG8-I to ATG8-II and increased level of autophagic flux. Such virus-containing autophagosomes seem able to mediate nonlytic viral release from cultured cells or facilitate viral spread in the leafhopper intestine. Applying the autophagy inhibitor 3-methyladenine or silencing the expression of Atg5 significantly decrease viral spread in vitro and in vivo, whereas applying the autophagy inducer rapamycin or silencing the expression of Torc1 facilitate such viral spread. Furthermore, we find that activation of autophagy facilitates efficient viral transmission, whereas inhibiting autophagy blocks viral transmission by its insect vector. Together, these results indicate a plant virus can induce the formation of autophagosomes for carrying virions, thus facilitating viral spread and transmission by its insect vector. We believe that such a role for virus-induced autophagy is common for vector-borne persistent viruses during their transmission by insect vectors.

Long-term resolution of delayed onset hypoglossal nerve palsy following occipital condyle fracture: Case report and review of the literature

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Sudhakar Vadivelu

2017-01-01

Full Text Available The authors present the case of a patient that demonstrates resolution of delayed onset hypoglossal nerve palsy (HNP subsequent to occipital condyle fracture following a motor vehicle accident. Decompression of the hypoglossal nerve and craniocervical fixation led to satisfactory long-term (>5 years outcome. There is a scarcity of literature in recognizing HNPs following trauma and a lack of pathophysiological understanding to both a delayed presentation and to resolution versus persistence. This is the first report demonstrating long-term resolution of hypoglossal nerve injury following trauma to the craniocervical junction.

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

Long-term contextual memory in infant rats as evidenced by an ethanol conditioned tolerance procedure.

Science.gov (United States)

Castelló, Stefanía; Molina, Juan Carlos; Arias, Carlos

2017-08-14

Conditioned tolerance can be conceptualized as a particular case of Pavlovian conditioning in which contextual cues play the role of the conditioned stimulus. Although the evidence is contradictory, it is frequently assumed that long-term contextual conditioning in pre-weanling rats is weak or even absent. This hypothesis comes from and is sustained mainly by behavioral studies that explored different contextual effects in 16-18day-old rats using a fear-conditioning paradigm, but their conclusions are stated in terms of an immature (hippocampal-dependent) declarative memory system. The main goal of the present manuscript was based on a recent antecedent from our laboratory, to analyze whether context-dependent tolerance induced by ethanol during the pre-weanling period persists over time. Results showed that the context was able to modulate ethanol-induced tolerance in 2- and 3-week-old rats. Interestingly, contextual conditioned tolerance was stronger (in terms of persistence) during the third than during the second postnatal week. When subjects were tested 8days after training, when the context presumably lost its influence over tolerance, the opposite effect emerged (sensitization). These results are important for the ethanol literature, adding new evidence of long-term retention of ethanol effects acquired during infancy, whilst also showing striking ontogenetic differences in the sensitivity to ethanol between the 2nd and 3rd postnatal weeks. Importantly, contextual information modulates the expression of these ethanol effects even eight days after training, a result that is particularly relevant to the discussion of the ontogeny of contextual memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term collections

CERN Multimedia

Collectes à long terme

2007-01-01

The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

Longitudinal variation in pressure injury incidence among long-term aged care facilities.

Science.gov (United States)

Jorgensen, Mikaela; Siette, Joyce; Georgiou, Andrew; Westbrook, Johanna I

2018-05-04

To examine variation in pressure injury (PI) incidence among long-term aged care facilities and identify resident- and facility-level factors that explain this variation. Longitudinal incidence study using routinely-collected electronic care management data. A large aged care service provider in New South Wales and the Australian Capital Territory, Australia. About 6556 people aged 65 years and older who were permanent residents in 60 long-term care facilities between December 2014 and November 2016. Risk-adjusted PI incidence rates over eight study quarters. Incidence density over the study period was 1.33 pressure injuries per 1000 resident days (95% confidence interval (CI) = 1.29-1.37). Funnel plots were used to identify variation among facilities. On average, 14% of facilities had risk-adjusted PI rates that were higher than expected in each quarter (above 95% funnel plot control limits). Ten percent of facilities had persistently high rates in any three or more consecutive quarters (n = 6). The variation between facilities was only partly explained by resident characteristics in multilevel regression models. Residents were more likely to have higher-pressure injury rates in facilities in regional areas compared with major city areas (adjusted incidence rate ratio = 1.25, 95% CI = 1.04-1.51), and facilities with persistently high rates were more likely to be located in areas with low socioeconomic status (P = 0.038). There is considerable variation among facilities in PI incidence. This study demonstrates the potential of routinely-collected care management data to monitor PI incidence and to identify facilities that may benefit from targeted intervention.

Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

Science.gov (United States)

Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

2012-01-01

Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

Sleeping Beauty-baculovirus hybrid vectors for long-term gene expression in the eye.

Science.gov (United States)

Turunen, Tytteli Anni Kaarina; Laakkonen, Johanna Päivikki; Alasaarela, Laura; Airenne, Kari Juhani; Ylä-Herttuala, Seppo

2014-01-01

A baculovirus vector is capable of efficiently transducing many nondiving and diving cell types. However, the potential of baculovirus is restricted for many gene delivery applications as a result of the transient gene expression that it mediates. The plasmid-based Sleeping Beauty (SB) transposon system integrates transgenes into target cell genome efficiently with a genomic integration pattern that is generally considered safer than the integration of many other integrating vectors; yet efficient delivery of therapeutic genes into cells of target tissues in vivo is a major challenge for nonviral gene therapy. In the present study, SB was introduced into baculovirus to obtain novel hybrid vectors that would combine the best features of the two vector systems (i.e. effective gene delivery and efficient integration into the genome), thus circumventing the major limitations of these vectors. We constructed and optimized SB-baculovirus hybrid vectors that bear either SB100x transposase or SB transposon in the forward or reverse orientations with respect to the viral backbone The functionality of the novel hybrid vectors was investigated in cell cultures and in a proof-of-concept study in the mouse eye. The hybrid vectors showed high and sustained transgene expression that remained stable and demonstrated no signs of decline during the 2 months follow-up in vitro. These results were verified in the mouse eye where persistent transgene expression was detected two months after intravitreal injection. Our results confirm that (i) SB-baculovirus hybrid vectors mediate long-term gene expression in vitro and in vivo, and (ii) the hybrid vectors are potential new tools for the treatment of ocular diseases. Copyright © 2014 John Wiley & Sons, Ltd.

Long-term respiratory health effects in textile workers.

Science.gov (United States)

Lai, Peggy S; Christiani, David C

2013-03-01

Over 60 million people worldwide work in the textile or clothing industry. Recent studies have recognized the contribution of workplace exposures to chronic lung diseases, in particular chronic obstructive pulmonary disease (COPD). Early studies in textile workers have focused on the relationship between hemp or cotton dust exposure and the development of a syndrome termed byssinosis. The purpose of this review is to evaluate the effect of long-term exposure to organic dust in textile workers on chronic respiratory disease in the broader context of disease classifications, such as reversible or irreversible obstructive lung disease (i.e. asthma or COPD), and restrictive lung disease. Cessation of exposure to cotton dust leads to improvement in lung function. Recent animal models have suggested a shift in the lung macrophage:dendritic cell population ratio as a potential mechanistic explanation for persistent inflammation in the lung due to repeated cotton dust-related endotoxin exposure. Other types of textile dust, such as silk, may contribute to COPD in textile workers. Textile dust-related obstructive lung disease has characteristics of both asthma and COPD. Significant progress has been made in the understanding of chronic lung disease due to organic dust exposure in textile workers.

Cost-effectiveness of longer-term versus shorter-term provision of antibiotics in patients with persistent symptoms attributed to Lyme disease

NARCIS (Netherlands)

Berende, A.; Nieuwenhuis, L.; Hofstede, H.J.M. ter; Vos, F.J.; Vogelaar, M.L.; Tromp, M.A.; Middendorp, H. van; Donders, A.R.T.; Evers, A.W.M.; Kullberg, B.J.; Adang, E.M.M.

2018-01-01

BACKGROUND: The treatment of persistent symptoms attributed to Lyme disease remains controversial. Recently, the PLEASE study did not demonstrate any additional clinical benefit of longer-term versus shorter-term antibiotic treatment. However, the economic impact of the antibiotic strategies has not

The energetic and chemical signatures of persistent soil organic matter

DEFF Research Database (Denmark)

Barré, Pierre; Plante, Alain F.; Cecillon, Lauric

2016-01-01

A large fraction of soil organic matter (OM) resists decomposition over decades to centuries as indicated by long radiocarbon residence times, but the mechanisms responsible for the long-term (multi-decadal) persistence are debated. The current lack of mechanistic understanding limits our ability...

Factors influencing long-term quality of life and depression in German liver transplant recipients: a single-centre cross-sectional study.

Science.gov (United States)

Zahn, Alexandra; Seubert, Lisa; Jünger, Jana; Schellberg, Dieter; Weiss, Karl Heinz; Schemmer, Peter; Stremmel, Wolfgang; Sauer, Peter; Gotthardt, Daniel Nils

2013-06-26

Health-related quality of life (HRQOL) following orthotopic liver transplantation (OLT) has become increasingly important. Therefore, we aimed to identify factors affecting HRQOL after OLT. This cross-sectional, single-centre study surveyed 281 OLT patients. Survey tools included the Short Form (SF-36) Health Survey, the Patient Health Questionnaire 9 (PHQ9), and a self-designed employment questionnaire. Patient medical records were reviewed. Participants included 187 men (mean age at OLT: 50 [± 11; 13-69] years). Primary indications for OLT were viral hepatitis (28%), alcoholic liver disease (35%), cholestatic liver disease (11%), and others (26%). Follow-up ranged from 2 to 136 months. Clinical factors associated with improved HRQOL were age ≤ 45 years at OLT and current MELD score <=≤ 13. Time after OLT and indication for transplantation affected SF-36 HRQOL. SF-36 physical component summary scales plateaued at 3-years post-OLT and then stabilized. For the SF-36 HRQOL, scores were the lowest in all domains for OLT recipients transplanted for chronic viral hepatitis and for unemployed patients, whereas sex and number of transplantations showed no significant differences. The PHQ9 results showed that depression was significantly more frequent among patients with current MELD score ≥ 13 or impaired liver function and those transplanted for chronic viral hepatitis or unemployed patients. Age and sex did not influence PHQ9 results. Medical and psychosocial support is crucial for long-term HRQOL after OLT. Developing multidisciplinary interventions to address issues such as employment, age, MELD score, and liver function may improve long-term HRQOL in these patients.

Long-term results of combined ESWL and ERCP treatment of chronic calcific pancreatitis.

Science.gov (United States)

Korpela, Taija; Udd, Marianne; Tenca, Andrea; Lindström, Outi; Halttunen, Jorma; Myrskysalo, Sanna; Mikkola, Arto; Kylänpää, Leena

2016-07-01

Extracorporeal shock wave lithotripsy (ESWL) combined with endotherapy (ET) is the standard treatment for pancreatic duct stones (PDS) in chronic pancreatitis (CP). Our aim was to report the short- and long-term results of ESWL and ET. Consecutively treated 83 patients with symptomatic PDS using ESWL and ET. Success was defined (i) technically: PDS fragmentation and clearance obtained and (ii) clinically: improvement/resolution of pain. To get information on quality of life, we conducted a phone survey whereby we contacted 64 (89%) patients. The long-term results are presented in those patients with ≥2 years follow-up. Treated PDS with median size of 10 (5-25) mm were located in the head, body, or the tail of the pancreas in 78, 4, and 1 patients, respectively. The primary results were that technical success was achieved in 69 patients (83%) and clinical success in 66 patients (80%). Fourteen patients had technical failure, but eight of them became free of pain. Thus, clinical success can be considered to have been achieved in 74 of 83 patients (89%). In patients with persistent pseudocyst (PC) at the time of ESWL (n = 19), the PC disappeared in a year in 14 patients (74%). The long-term results were obtained from 61 (73%) ESWL- and ET-treated patients. The median follow-up for them was 53 months (range: 24-124) and 57 patients (93%) became pain-free or had less pain. For patients with CP and PDS ESWL combined with ET is an effective and safe treatment giving favorable long-term results.

Viral factor TAV recruits TOR/S6K1 signalling to activate reinitiation after long ORF translation

Science.gov (United States)

Schepetilnikov, Mikhail; Kobayashi, Kappei; Geldreich, Angèle; Caranta, Carole; Robaglia, Christophe; Keller, Mario; Ryabova, Lyubov A

2011-01-01

The protein kinase TOR (target-of-rapamycin) upregulates translation initiation in eukaryotes, but initiation restart after long ORF translation is restricted by largely unknown pathways. The plant viral reinitiation factor transactivator–viroplasmin (TAV) exceptionally promotes reinitiation through a mechanism involving retention on 80S and reuse of eIF3 and the host factor reinitiation-supporting protein (RISP) to regenerate reinitiation-competent ribosomal complexes. Here, we show that TAV function in reinitiation depends on physical association with TOR, with TAV–TOR binding being critical for both translation reinitiation and viral fitness. Consistently, TOR-deficient plants are resistant to viral infection. TAV triggers TOR hyperactivation and S6K1 phosphorylation in planta. When activated, TOR binds polyribosomes concomitantly with polysomal accumulation of eIF3 and RISP—a novel and specific target of TOR/S6K1—in a TAV-dependent manner, with RISP being phosphorylated. TAV mutants defective in TOR binding fail to recruit TOR, thereby abolishing RISP phosphorylation in polysomes and reinitiation. Thus, activation of reinitiation after long ORF translation is more complex than previously appreciated, with TOR/S6K1 upregulation being the key event in the formation of reinitiation-competent ribosomal complexes. PMID:21343906

Long persistent luminescence property of a novel green emitting SrLaGaO{sub 4}: Tb{sup 3+} phosphor

Energy Technology Data Exchange (ETDEWEB)

Fu, Xiaoyan, E-mail: fuxiaoyan@xmut.edu.cn [College of Materials Science and Engineering, Xiamen University of Technology, Xiamen 361024 (China); Jiangsu Collaborative Innovation Center of Atmospheric Environment and Equipment Technology (CICAEET), Nanjing University of Information Science & Technology, Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control (AEMPC), Nanjing 210044 (China); Zheng, Shenghui [College of Materials Science and Engineering, Xiamen University of Technology, Xiamen 361024 (China); Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Shi, Junpeng [Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Li, Yuechan [College of Materials Science and Engineering, Xiamen University of Technology, Xiamen 361024 (China); Zhang, Hongwu, E-mail: hwzhang@iue.ac.cn [Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China)

2017-04-15

A novel long persistent green emitting phosphor SrLaGaO{sub 4}: Tb{sup 3+} was synthesized via a conventional high temperature solid-state method. The obtained results indicated that the green long persistent emitting was similar to the photoluminescence, originating from the f-f transitions of Tb{sup 3+} centers which were supposed to occupy the random distribution Sr{sup 2+} and La{sup 3+} sites. The duration of green afterglow can be observed in the dark by naked eyes even after more than 3.5 h. The thermoluminescence results revealed that SrLaGaO{sub 4}: Tb{sup 3+} possessed three main traps calculated to be 0.62, 0.68 and 0.77 eV, which were responsible for the long persistent green luminescence. The further structure analysis revealed that the Tb{sup 3+} dopants not only acted as emission centers but also significantly influenced the density of traps, and the trapping centers were postulated nonrandom distribution under the assistance of high temperature, which resulted in the efficient persistent luminescence of Tb{sup 3+}. All the results showed that SrLaGaO{sub 4}: Tb{sup 3+} was a potential long persistent luminescent material.

Sexuality and Physical Intimacy in Long Term Care: Sexuality, long term care, capacity assessment

OpenAIRE

Lichtenberg, Peter A.

2014-01-01

Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literatur...

Differences in health status between long-term and short-term benzodiazepine users.

NARCIS (Netherlands)

Zandstra, S.M.; Furer, J.W.; Lisdonk, E.H. van de; Bor, J.H.J.; Zitman, F.G.; Weel, C. van

2002-01-01

BACKGROUND: Despite generally accepted advice to keep treatment short, benzodiazepines are often prescibed for more than six months. Prevention of long-term benzodiazepine use could be facilitated by the utilisation of risk indicators for long-term use. However, the characteristics of long-term

Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

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Gosz, J.

2001-12-01

The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

Federal funding for syringe exchange in the US: Explaining a long-term policy failure.

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Showalter, David

2018-05-01

The United States prohibited federal funding for syringe exchange programs for people who inject drugs nearly continuously from 1988 to 2015, despite growing scientific evidence, diminishing AIDS-related controversy, and tens of thousands of deaths from injection-related AIDS. This study investigates the political and institutional bases of this long-term failure to support lifesaving public policy. This study draws on national, regional, and local media coverage, archival sources, and semi-structured, in-depth interviews with 6 long-time syringe exchange researchers and activists from California. I use case-oriented process tracing methods to explain the persistence and reform of the federal funding ban. Though previous studies focus on the symbolic clash between conservative morality and empirical science, I find that changing demographic and regional inequalities in the effects of the AIDS epidemic and dynamics produced by the federal structure of US government were more important factors in the creation and persistence of the funding ban. The persistence and eventual repeal of the ban on federal funding for syringe exchange was a product of the changing demographic, geographic, and political effects of the AIDS epidemic within the federal structure of US government, rather than a consequence of intractable morality politics. These contextual dynamics continue to shape AIDS and public health policy at all levels of government. Copyright © 2018. Published by Elsevier B.V.

Self-Reported Long-Term Benefits of Mindfulness-Based Cognitive Therapy in Patients with Bipolar Disorder.

Science.gov (United States)

Weber, Béatrice; Sala, Loretta; Gex-Fabry, Marianne; Docteur, Aurélie; Gorwood, Philip; Cordera, Paolo; Bondolfi, Guido; Jermann, Françoise; Aubry, Jean-Michel; Mirabel-Sarron, Christine

2017-07-01

This study focused on patients with bipolar disorder (BD), several years after their participation in mindfulness-based cognitive therapy (MBCT). It aimed at documenting sustained mindfulness practice, perceived long-term benefit from the program, and changes regarded as direct consequences of the intervention. This cross-sectional survey took place at least 2 years after MBCT for 70.4% of participants. It was conducted in two specialized outpatient units for BDs that are part of the Geneva University Hospitals (Switzerland) and the Sainte-Anne Hospital in Paris (France). Eligibility criteria were a diagnosis of BD according to DSM-IV and participation in at least four MBCT sessions. Response rate was 66.4%. The final sample included 71 outpatients (71.8% bipolar I, 28.2% bipolar II). A questionnaire retrospectively assessed patient-perceived change, benefit from MBCT, and current mindfulness practice. Proportions of respondents who practiced mindfulness at least once a week were 54.9% for formal practice (body scan, sitting meditation, mindful walking, or movements) and 57.7% for informal practice (mindful daily activities). Perceived benefit for the prevention of relapse was moderate, but patients acknowledged long-lasting effects and persistent changes in their way of life. Formal mindfulness practice at least once a week tended to be associated with increased long-lasting effects (p = 0.052), whereas regular informal practice and mindful breathing were significantly associated with persistent changes in daily life (p = 0.038) and better prevention of depressive relapse (p = 0.035), respectively. The most frequently reported positive change was increased awareness of being able to improve one's health. Despite methodological limitations, this survey allowed documenting mindfulness practice and perceived sustained benefit from MBCT in patients with BD. Participants particularly valued increased awareness that they can influence their own health. Both

Latent viral reactivation is associated with changes in plasma antimicrobial protein concentrations during long-duration spaceflight

Science.gov (United States)

Spielmann, G.; Laughlin, M. S.; Kunz, H.; Crucian, B. E.; Quiriarte, H. D.; Mehta, S. K.; Pierson, D. L.; Simpson, R. J.

2018-05-01

Long duration spaceflights are associated with profound dysregulation of the immune system and latent viral reactivations. However, little is known on the impact of long duration spaceflight on innate immunity which raises concerns on crewmembers' ability to fight infections during a mission. The aim of this study was to determine the effects of spaceflight on plasma antimicrobial proteins (AMPs) and how these changes impact latent herpesvirus reactivations. Plasma, saliva and urine samples were obtained from 23 crewmembers before, during and after a 6-month mission on the International Space Station (ISS). Plasma AMP concentrations were determined by ELISA, and saliva Epstein-Barr virus (EBV) and varicella zoster virus (VZV) and urine cytomegalovirus (CMV) DNA levels were quantified by Real-Time PCR. There was a non-significant increase in plasma HNP1-3 and LL-37 during the early and middle stages of the missions, which was significantly associated with changes in viral DNA during and after spaceflight. Plasma HNP1-3 and Lysozyme increased at the late mission stages in astronauts who had exhibited EBV and VZV reactivations during the early flight stages. Following return to Earth and during recovery, HNP1-3 and lysozyme concentrations were associated with EBV and VZV viral DNA levels, reducing the magnitude of viral reactivation. Reductions in plasma LL-37 upon return were associated with greater CMV reactivation. This study shows that biomarkers of innate immunity appeared to be partially restored after 6-months in space and suggests that following adaptation to the space environment, plasma HNP1-3 and lysozyme facilitate the control of EBV and VZV reactivation rate and magnitude in space and upon return on earth. However, the landing-associated decline in plasma LL-37 may enhance the rate of CMV reactivation in astronauts following spaceflight, potentially compromising crewmember health after landing.

Epidemiology of respiratory viral infections in two long-term refugee camps in Kenya, 2007-2010

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Ahmed Jamal A

2012-01-01

Full Text Available Abstract Background Refugees are at risk for poor outcomes from acute respiratory infections (ARI because of overcrowding, suboptimal living conditions, and malnutrition. We implemented surveillance for respiratory viruses in Dadaab and Kakuma refugee camps in Kenya to characterize their role in the epidemiology of ARI among refugees. Methods From 1 September 2007 through 31 August 2010, we obtained nasopharyngeal (NP and oropharyngeal (OP specimens from patients with influenza-like illness (ILI or severe acute respiratory infections (SARI and tested them by RT-PCR for adenovirus (AdV, respiratory syncytial virus (RSV, human metapneumovirus (hMPV, parainfluenza viruses (PIV, and influenza A and B viruses. Definitions for ILI and SARI were adapted from those of the World Health Organization. Proportions of cases associated with viral aetiology were calculated by camp and by clinical case definition. In addition, for children Results We tested specimens from 1815 ILI and 4449 SARI patients (median age = 1 year. Proportion positive for virus were AdV, 21.7%; RSV, 12.5%; hMPV, 5.7%; PIV, 9.4%; influenza A, 9.7%; and influenza B, 2.6%; 49.8% were positive for at least one virus. The annual rate of SARI hospitalisation for 2007-2010 was 57 per 1000 children per year. Virus-positive hospitalisation rates were 14 for AdV; 9 for RSV; 6 for PIV; 4 for hMPV; 5 for influenza A; and 1 for influenza B. The rate of SARI hospitalisation was highest in children Conclusions Respiratory viral infections, particularly RSV and AdV, were associated with high rates of illness and make up a substantial portion of respiratory infection in these two refugee settings.

Long term weight maintenance after advice to consume low carbohydrate, higher protein diets--a systematic review and meta analysis.

Science.gov (United States)

Clifton, P M; Condo, D; Keogh, J B

2014-03-01

Meta analysis of short term trials indicates that a higher protein, lower carbohydrate weight loss diet enhances fat mass loss and limits lean mass loss compared with a normal protein weight loss diet. Whether this benefit persists long term is not clear. We selected weight loss studies in adults with at least a 12 month follow up in which a higher percentage protein/lower carbohydrate diet was either planned or would be expected for either weight loss or weight maintenance. Studies were selected regardless of the success of the advice but difference in absolute and percentage protein intake at 12 months was used as a moderator in the analysis. Data was analysed using Comprehensive Meta analysis V2 using a random effects analysis. As many as 32 studies with 3492 individuals were analysed with data on fat and lean mass, glucose and insulin from 18 to 22 studies and lipids from 28 studies. A recommendation to consume a lower carbohydrate, higher protein diet in mostly short term intensive interventions with long term follow up was associated with better weight and fat loss but the effect size was small-standardised means of 0.14 and 0.22, p = 0.008 and p fat mass (0.9 vs. 0.3 kg). Fasting triglyceride and insulin were also lower with high protein diets with effect sizes of 0.17 and 0.22, p = 0.003 and p = 0.042 respectively. Other lipids and glucose were not different. The short term benefit of higher protein diets appears to persist to a small degree long term. Benefits are greater with better compliance to the diet. Copyright © 2013 Elsevier B.V. All rights reserved.

Very long-term sequelae of craniopharyngioma.

Science.gov (United States)

Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

2017-06-01

Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

Long-term prisoner in prison isolation

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Karolina Grudzińska

2013-06-01

Full Text Available Long-term prisoner belongs to a particular category of people who are imprisoned in prisons. On the one hand in this group are often heavily demoralized people who committed the most serious crimes, on the other hand it is a group of prisoners, who should be well thought out and programmed the impact of rehabilitation. The situation of man trapped for years poses in a complicated situation not only the prisoners, but also the entire prison staff. They have to take care of the fact that the prison isolation did not cause the state in which convicts form itself in learned helplessness and lack of skills for self-planning and decision-making. In addition, planning the rehabilitation impact of long-term prisoners should not be forgotten that these prisoners in the short or the long term will return to the libertarian environment therefore, should prevent any negative effects of long-term imprisonment. This article presents the main issues related to the execution of imprisonment against long-term prisoners. It is an attempt to systematize the knowledge of this category of people living in prison isolation.

Long-term disturbance dynamics and resilience of tropical peat swamp forests.

Science.gov (United States)

Cole, Lydia E S; Bhagwat, Shonil A; Willis, Katherine J

2015-01-01

1. The coastal peat swamp forests of Sarawak, Malaysian Borneo, are undergoing rapid conversion, predominantly into oil palm plantations. This wetland ecosystem is assumed to have experienced insignificant disturbance in the past, persisting under a single ecologically-stable regime. However, there is limited knowledge of the past disturbance regime, long-term functioning and fundamentally the resilience of this ecosystem to changing natural and anthropogenic perturbations through time. 2. In this study, long-term ecological data sets from three degraded peatlands in Sarawak were collected to shed light on peat swamp forest dynamics. Fossil pollen and charcoal were counted in each sedimentary sequence to reconstruct vegetation and investigate responses to past environmental disturbance, both natural and anthropogenic. 3. Results demonstrate that peat swamp forest taxa have dominated these vegetation profiles throughout the last c . 2000-year period despite the presence of various drivers of disturbance. Evidence for episodes of climatic variability, predominantly linked to ENSO events, and wildfires is present throughout. However, in the last c . 500 years, burning and indicators of human disturbance have elevated beyond past levels at these sites, concurrent with a reduction in peat swamp forest pollen. 4. Two key insights have been gained through this palaeoecological analysis: (i) peat swamp forest vegetation has demonstrated resilience to disturbance caused by burning and climatic variability in Sarawak in the late Holocene, however (ii) coincident with increased fire combined with human impact c . 500 years ago, these communities started to decline. 5. Synthesis . Sarawak's coastal peat swamps have demonstrated resilience to past natural disturbances, with forest vegetation persisting through episodes of fire and climatic variability. However, palaeoecological data presented here suggest that recent, anthropogenic disturbances are of a greater magnitude

Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats.

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Hila Abush

Full Text Available The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg for two weeks during the late adolescence period (post-natal days 45-60 and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP in the ventral subiculum (vSub-nucleus accumbens (NAc pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

The human vascular endothelial cell line HUV-EC-C harbors the integrated HHV-6B genome which remains stable in long term culture.

Science.gov (United States)

Shioda, Setsuko; Kasai, Fumio; Ozawa, Midori; Hirayama, Noriko; Satoh, Motonobu; Kameoka, Yousuke; Watanabe, Ken; Shimizu, Norio; Tang, Huamin; Mori, Yasuko; Kohara, Arihiro

2018-02-01

Human herpes virus 6 (HHV-6) is a common human pathogen that is most often detected in hematopoietic cells. Although human cells harboring chromosomally integrated HHV-6 can be generated in vitro, the availability of such cell lines originating from in vivo tissues is limited. In this study, chromosomally integrated HHV-6B has been identified in a human vascular endothelial cell line, HUV-EC-C (IFO50271), derived from normal umbilical cord tissue. Sequence analysis revealed that the viral genome was similar to the HHV-6B HST strain. FISH analysis using a HHV-6 DNA probe showed one signal in each cell, detected at the distal end of the long arm of chromosome 9. This was consistent with a digital PCR assay, validating one copy of the viral DNA. Because exposure of HUV-EC-C to chemicals did not cause viral reactivation, long term cell culture of HUV-EC-C was carried out to assess the stability of viral integration. The growth rate was altered depending on passage numbers, and morphology also changed during culture. SNP microarray profiles showed some differences between low and high passages, implying that the HUV-EC-C genome had changed during culture. However, no detectable change was observed in chromosome 9, where HHV-6B integration and the viral copy number remained unchanged. Our results suggest that integrated HHV-6B is stable in HUV-EC-C despite genome instability.

Competitive short-term and long-term memory processes in spatial habituation.

Science.gov (United States)

Sanderson, David J; Bannerman, David M

2011-04-01

Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory.

Bayesian evidence and epidemiological implications of environmental contamination from acute respiratory infection in long-term care facilities.

Science.gov (United States)

Diaz-Decaro, J D; Launer, B; Mckinnell, J A; Singh, R; Dutciuc, T D; Green, N M; Bolaris, M; Huang, S S; Miller, L G

2018-05-01

Skilled nursing home facilities (SNFs) house a vulnerable population frequently exposed to respiratory pathogens. Our study aims to gain a better understanding of the transmission of nursing home-acquired viral respiratory infections in non-epidemic settings. Symptomatic surveillance was performed in three SNFs for residents exhibiting acute respiratory symptoms. Environmental surveillance of five high-touch areas was performed to assess possible transmission. All resident and environmental samples were screened using a commercial multiplex polymerase chain reaction platform. Bayesian methods were used to evaluate environmental contamination. Among nursing home residents with respiratory symptoms, 19% had a detectable viral pathogen (parainfluenza-3, rhinovirus/enterovirus, RSV, or influenza B). Environmental contamination was found in 20% of total room surface swabs of symptomatic residents. Environmental and resident results were all concordant. Target period prevalence among symptomatic residents ranged from 5.5 to 13.3% depending on target. Bayesian analysis quantifies the probability of environmental shedding due to parainfluenza-3 as 92.4% (95% CI: 86.8-95.8%) and due to rhinovirus/enterovirus as 65.6% (95% CI: 57.9-72.5%). Our findings confirm that non-epidemic viral infections are common among SNF residents exhibiting acute respiratory symptoms and that environmental contamination may facilitate further spread with considerable epidemiological implications. Findings further emphasise the importance of environmental infection control for viral respiratory pathogens in long-term care facilities.

Long-Term Memory: A Natural Mechanism for the Clustering of Extreme Events and Anomalous Residual Times in Climate Records

Science.gov (United States)

Bunde, Armin; Eichner, Jan F.; Kantelhardt, Jan W.; Havlin, Shlomo

2005-01-01

We study the statistics of the return intervals between extreme events above a certain threshold in long-term persistent records. We find that the long-term memory leads (i)to a stretched exponential distribution of the return intervals, (ii)to a pronounced clustering of extreme events, and (iii)to an anomalous behavior of the mean residual time to the next event that depends on the history and increases with the elapsed time in a counterintuitive way. We present an analytical scaling approach and demonstrate that all these features can be seen in long climate records. The phenomena should also occur in heartbeat records, Internet traffic, and stock market volatility and have to be taken into account for an efficient risk evaluation.

Long term liquidity analysis of the firm

Directory of Open Access Journals (Sweden)

Jaroslav Gonos

2009-09-01

Full Text Available Liquidity control is a very difficult and important function. If the business is not liquid in the long term, it is under threatof bankruptcy, and on the other hand surplus of the cash in hand threaten its future efficiency, because the cash in hand is a sourceof only limited profitability. Long term liquidity is related to the ability of the short term and long term liabilities payment. Articleis trying to point out to the monitoring and analyzing of the long term liquidity in the concrete business, in this case the printing industrycompany. Hereby at the end of the article mentioned monitored and analyzed liquidity is evaluated in the five years time period.

Bronchopulmonary Dysplasia: Chronic Lung Disease of Infancy and Long-Term Pulmonary Outcomes

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Lauren M. Davidson

2017-01-01

Full Text Available Bronchopulmonary dysplasia (BPD is a chronic lung disease most commonly seen in premature infants who required mechanical ventilation and oxygen therapy for acute respiratory distress. While advances in neonatal care have resulted in improved survival rates of premature infants, limited progress has been made in reducing rates of BPD. Lack of progress may in part be attributed to the limited therapeutic options available for prevention and treatment of BPD. Several lung-protective strategies have been shown to reduce risks, including use of non-invasive support, as well as early extubation and volume ventilation when intubation is required. These approaches, along with optimal nutrition and medical therapy, decrease risk of BPD; however, impacts on long-term outcomes are poorly defined. Characterization of late outcomes remain a challenge as rapid advances in medical management result in current adult BPD survivors representing outdated neonatal care. While pulmonary disease improves with growth, long-term follow-up studies raise concerns for persistent pulmonary dysfunction; asthma-like symptoms and exercise intolerance in young adults after BPD. Abnormal ventilatory responses and pulmonary hypertension can further complicate disease. These pulmonary morbidities, combined with environmental and infectious exposures, may result in significant long-term pulmonary sequalae and represent a growing burden on health systems. Additional longitudinal studies are needed to determine outcomes beyond the second decade, and define risk factors and optimal treatment for late sequalae of disease.

Microneedle-mediated delivery of viral vectored vaccines.

Science.gov (United States)

Zaric, Marija; Ibarzo Yus, Bárbara; Kalcheva, Petya Petrova; Klavinskis, Linda Sylvia

2017-10-01

Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious delivery of different vaccine formulations, including viral vectors. Areas covered: Attributes and challenges of the most promising viral vector candidates that have advanced to the clinic and that have been leveraged for skin delivery by microneedles; The importance of understanding the immunobiology of antigen-presenting cells in the skin, in particular dendritic cells, in order to generate further improved skin vaccination strategies; recent studies where viral vectors expressing various antigens have been coupled with microneedle technology to examine their potential for improved vaccination. Expert opinion: Simple, economic and efficacious vaccine delivery methods are needed to improve health outcomes and manage possible outbreaks of new emerging viruses. Understanding what innate/inflammatory signals are required to induce both immediate and long-term responses remains a major hurdle in the development of the effective vaccines. One approach to meet these needs is microneedle-mediated viral vector vaccination. In order for this technology to fulfil this potential the industry must invest significantly to further develop its design, production, biosafety, delivery and large-scale manufacturing.

Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension.

Science.gov (United States)

Fein, Henry G; Vaughan, T Brooks; Kushner, Harvey; Cram, David; Nguyen, Dat

2015-10-27

Overweight and obesity are common among patients with Cushing's syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults (N = 50) with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had failed or were not candidates for surgery (SEISMIC, Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome). This analysis examines long-term weight change among patients who received mifepristone in SEISMIC and enrolled in a long-term safety extension (LTE) study. Patients completing the 24-week SEISMIC study and subsequent 6-week off-drug safety evaluation were invited to enroll in the LTE study. Mifepristone doses at the end of SEISMIC were the LTE starting doses. Body weight measures were reviewed at baseline and week 24 of SEISMIC and at LTE month 6, 12, 18, 24, and final visit (last observation collected during the LTE study). Of the 30 patients enrolled in the LTE, evaluable weight data were available for 29 (20/29 female; mean age of 44.7 ± 11.2 years). These patients received mifepristone for a median of 29.2 months (range 8.4-41.9). Mean ± SD weight from SEISMIC baseline to LTE final visit decreased by 10.3 ± 16.3 kg (mean 105.4 ± 34.3 kg to 95.1 ± 32.9 kg), a 9.3 % decrease from baseline weight (P = 0.0008). Of the 29 LTE patients, 18 (62.1 %) lost ≥ 5 % of body weight by the end of the initial 24-week treatment period; this ≥5 % weight loss persisted in 83.3 % (15/18) at LTE final visit. Ten patients (34.5 %) lost ≥ 10 % of initial body weight by week 24 of SEISMIC, which persisted in 80 % at LTE final visit. No new safety signals were detected with long-term mifepristone use. Clinically meaningful weight loss achieved during

Long-term contracts vs. short-term trade of natural gas - a European perspective

International Nuclear Information System (INIS)

Neuhoff, Karsten; Hirschhausen, Christian von

2005-01-01

This paper analyses the economics of long-term gas contracts under changing institutional conditions, mainly gas sector liberalisation. The paper is motivated by the increasingly tense debate in continental Europe, UK and the US on the security of long-term gas supply. We discuss the main issues regarding long-term contracts, i.e. the changing role of the flexibility clause, the effect of abandoning the destination clause, and the strategic behaviour of producers between long-term sales and spot-sales. The literature suggests consumers and producers benefit from risk hedging through long-term contracts. Furthermore long-term contracts may reduce exercise of market power. Our analysis adds an additional benefit if the long-run demand elasticity is significantly lower than the short-run elasticity, both strategic producers and consumers benefit from lower prices and larger market volume. Some policy implications of the findings are also discussed. (Author)

The uranium industry: long-term planning for short-term competition

International Nuclear Information System (INIS)

Vottero, X.; Georges Capus, G.

2001-01-01

Long term planning for short term competition Today, uranium producers face new challenges in terms of both production (new regulatory, environmental and social constraints) and market conditions (new sources of uranium supply, very low prices and tough competition). In such a context, long-term planning is not just a prerequisite to survive in the nuclear fuel cycle industry. In fact, it also contributes to sustaining nuclear electricity generation facing fierce competition from other energy sources in increasingly deregulated markets. Firstly, the risk of investing in new mining projects in western countries is growing because, on the one hand, of very erratic market conditions and, on the other hand, of increasingly lengthy, complex and unpredictable regulatory conditions. Secondly, the supply of other sources of uranium (uranium derived from nuclear weapons, uranium produced in CIS countries, ...) involve other risks, mainly related to politics and commercial restrictions. Consequently, competitive uranium supply requires not only technical competence but also financial strength and good marketing capabilities in order to anticipate long-term market trends, in terms of both demand and supply. It also requires taking into account new parameters such as politics, environment, regulations, etc. Today, a supplier dedicated to the sustainable production of nuclear electricity must manage a broad range of long-term risks inherent to the procurement of uranium. Taking into account all these parameters in a context of short-term, fast-changing market is a great challenge for the future generation. World Uranium Civilian Supply and Demand. (authors)

Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions.

Science.gov (United States)

Weber, Matheus N; Bauermann, Fernando V; Canal, Cláudio W; Bayles, Darrell O; Neill, John D; Ridpath, Julia F

2017-01-02

'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. An increase in genetic variability and the development of certain mutations was observed over time. Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. It is hypothesized that these changes may be the results on continued adaption of the pestivirus to individual hosts. This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. Published by Elsevier B.V.

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

Long-term symptomatic, functional, and work outcomes of carpal tunnel syndrome among construction workers.

Science.gov (United States)

Evanoff, Bradley; Gardner, Bethany T; Strickland, Jaime R; Buckner-Petty, Skye; Franzblau, Alfred; Dale, Ann Marie

2016-05-01

The long-term outcomes of carpal tunnel syndrome (CTS) including symptoms, functional status, work disability, and economic impact are unknown. We conducted a retrospective study of 234 active construction workers with medical claims for CTS and 249 workers without CTS claims; non-cases were matched on age, trade, and insurance eligibility. We conducted telephone interviews with cases and non-cases and collected administrative data on work hours. Compared to non-cases, CTS cases were more likely to report recurrent hand symptoms, decreased work productivity/quality, decreased performance of physical work demands, and greater functional limitations. Surgical cases showed larger improvements on multiple outcomes than non-surgical cases. Minimal differences in paid work hours were seen between cases and non-cases in the years preceding and following CTS claims. Persistent symptoms and functional impairments were present several years after CTS diagnosis. Long-term functional limitations shown by this and other studies indicate the need for improved prevention and treatment. © 2016 Wiley Periodicals, Inc.

Long-term biodosimetry Redux

International Nuclear Information System (INIS)

Simon, Steven L.; Bouville, Andre

2016-01-01

This paper revisits and reiterates the needs, purposes and requirements of bio-dosimetric assays for long-term dose and health risk assessments. While the most crucial need for bio-dosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure

Long term radioactive waste management

International Nuclear Information System (INIS)

Lavie, J.M.

1984-01-01

In France, waste management, a sensitive issue in term of public opinion, is developing quickly, and due to twenty years of experience, is now reaching maturity. With the launching of the French nuclear programme, the use of radioactive sources in radiotherapy and industry, waste management has become an industrial activity. Waste management is an integrated system dealing with the wastes from their production to the long term disposal, including their identification, sortage, treatment, packaging, collection and transport. This system aims at guaranteing the protection of present and future populations with an available technology. In regard to their long term management, and the design of disposals, radioactive wastes are divided in three categories. This classification takes into account the different radioisotopes contained, their half life and their total activity. Presently short-lived wastes are stored in the shallowland disposal of the ''Centre de la Manche''. Set up within the French Atomic Energy Commission (CEA), the National Agency for waste management (ANDRA) is responsible within the framework of legislative and regulatory provisions for long term waste management in France [fr

FIVE-YEAR OUTCOMES AFTER LONG-TERM OXANDROLONE ADMINISTRATION IN SEVERELY BURNED CHILDREN: A RANDOMIZED CLINICAL TRIAL

OpenAIRE

Reeves, Patrick T; Herndon, David N; Tanksley, Jessica D; Jennings, Kristofer; Klein, Gordon L; Mlcak, Ronald P; Clayton, Robert P; Crites, Nancy N; Hays, Joshua P; Andersen, Clark; Lee, Jong O; Meyer, Walter; Suman, Oscar E; Finnerty, Celeste C

2016-01-01

Administration of oxandrolone, a non-aromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of oxandrolone administration. This study was undertaken to determine if administration of oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD...

Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management.

Directory of Open Access Journals (Sweden)

Gergana Galabova

Full Text Available Low Density Lipoprotein (LDL hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9 to modulate circulating LDL cholesterol (LDLc concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models.PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt mice, Ldlr+/- mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested.Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans.

Modeling long-term dynamics of electricity markets

International Nuclear Information System (INIS)

Olsina, Fernando; Garces, Francisco; Haubrich, H.-J.

2006-01-01

In the last decade, many countries have restructured their electricity industries by introducing competition in their power generation sectors. Although some restructuring has been regarded as successful, the short experience accumulated with liberalized power markets does not allow making any founded assertion about their long-term behavior. Long-term prices and long-term supply reliability are now center of interest. This concerns firms considering investments in generation capacity and regulatory authorities interested in assuring the long-term supply adequacy and the stability of power markets. In order to gain significant insight into the long-term behavior of liberalized power markets, in this paper, a simulation model based on system dynamics is proposed and the underlying mathematical formulations extensively discussed. Unlike classical market models based on the assumption that market outcomes replicate the results of a centrally made optimization, the approach presented here focuses on replicating the system structure of power markets and the logic of relationships among system components in order to derive its dynamical response. The simulations suggest that there might be serious problems to adjust early enough the generation capacity necessary to maintain stable reserve margins, and consequently, stable long-term price levels. Because of feedback loops embedded in the structure of power markets and the existence of some time lags, the long-term market development might exhibit a quite volatile behavior. By varying some exogenous inputs, a sensitivity analysis is carried out to assess the influence of these factors on the long-run market dynamics

Short-term memory and long-term memory are still different.

Science.gov (United States)

Norris, Dennis

2017-09-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology-the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as "1, 3, 1" where there are 2 tokens of the digit "1" cannot be stored in the correct order simply by activating the representations of the digits "1" and "3" in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation*

Science.gov (United States)

Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert

2016-01-01

Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation.

Science.gov (United States)

Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert; Michaelevski, Izhak

2016-02-01

Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

Long-Term Collections

CERN Multimedia

Comité des collectes à long terme

2011-01-01

It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

NaVirCept - Nucleic Acid-Based Anti-Viral Project

International Nuclear Information System (INIS)

Stephen, E. R.; Wong, J.; Van Loon, D.

2007-01-01

Vaccines are generally considered to be the most effective countermeasures to bacterial and viral diseases, however, licensed vaccines against many disease agents are either not available or their efficacies have not been demonstrated. Vaccines are generally agent specific in terms of treatment spectrum and are subject to defeat through natural mutation or through directed efforts. With respect to viral therapeutics, one of the major limitations associated with antiviral drugs is acquired drug resistance caused by antigenic shift or drift. A number of next-generation prophylactic and/or therapeutic measures are on the horizon. Of these, nucleic acid-based drugs are showing great antiviral potential. These drugs elicit long-lasting, broad spectrum protective immune responses, especially to respiratory viral pathogens. The Nucleic Acid-Based Antiviral (NaVirCept) project provides the opportunity to demonstrate the effectiveness of novel medical countermeasures against military-significant endemic and other viral threat agents. This project expands existing DRDC drug delivery capability development, in the form of proprietary liposome intellectual property, by coupling it with leading-edge nucleic acid-based technology to deliver effective medical countermeasures that will protect deployed personnel and the warfighter against a spectrum of viral disease agents. The technology pathway will offer a means to combat emerging viral diseases or modified threat agents such as the bird flu or reconstructed Spanish flu without going down the laborious, time-consuming and expensive paths to develop countermeasures for each new and/or emerging viral disease organism.(author)

MR observations of long-term musculotendon remodeling following a hamstring strain injury

International Nuclear Information System (INIS)

Silder, Amy; Heiderscheit, Bryan C.; Thelen, Darryl G.; Enright, Timothy; Tuite, Michael J.

2008-01-01

The objective of this study was to use magnetic resonance (MR) imaging to investigate long-term changes in muscle and tendon morphology following a hamstring strain injury. MR images were obtained from 14 athletes who sustained a clinically diagnosed grade I-II hamstring strain injury between 5 and 23 months prior as well as five healthy controls. Qualitative bilateral comparisons were used to assess the presence of fatty infiltration and changes in morphology that may have arisen as a result of the previous injury. Hamstring muscle and tendon-scar volumes were quantified in both limbs for the biceps femoris long head (BFLH), biceps femoris short head (BFSH), the proximal semimembranosus tendon, and the proximal conjoint biceps femoris and semitendinosus tendon. Differences in muscle and tendon volume between limbs were statistically compared between the previously injured and healthy control subjects. Increased low-intensity signal was present along the musculotendon junction adjacent to the site of presumed prior injury for 11 of the 14 subjects, suggestive of persistent scar tissue. The 13 subjects with biceps femoris injuries displayed a significant decrease in BFLH volume (p < 0.01), often accompanied by an increase in BFSH volume. Two of these subjects also presented with fatty infiltration within the previously injured BFLH. The results of this study provide evidence of long-term musculotendon remodeling following a hamstring strain injury. Additionally, many athletes are likely returning to sport with residual atrophy of the BFLH and/or hypertrophy of the BFSH. It is possible that long-term changes in musculotendon structure following injury alters contraction mechanics during functional movement, such as running and may contribute to reinjury risk. (orig.)

MR observations of long-term musculotendon remodeling following a hamstring strain injury

Energy Technology Data Exchange (ETDEWEB)

Silder, Amy [University of Wisconsin, Madison, WI (US). Department of Biomedical Engineering, Madison, WI (United States); Heiderscheit, Bryan C. [University of Wisconsin, Madison, WI (US). Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin, Madison, WI (US). Department of Orthopedics and Rehabilitation, Madison, WI (United States); Thelen, Darryl G. [University of Wisconsin, Madison, WI (US). Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin, Madison, WI (US). Department of Orthopedics and Rehabilitation, Madison, WI (United States); University of Wisconsin, Madison, WI (US). Department of Mechanical Engineering, Madison, WI (United States); Enright, Timothy; Tuite, Michael J. [University of Wisconsin, Madison, WI (United States). Department of Radiology

2008-12-15

The objective of this study was to use magnetic resonance (MR) imaging to investigate long-term changes in muscle and tendon morphology following a hamstring strain injury. MR images were obtained from 14 athletes who sustained a clinically diagnosed grade I-II hamstring strain injury between 5 and 23 months prior as well as five healthy controls. Qualitative bilateral comparisons were used to assess the presence of fatty infiltration and changes in morphology that may have arisen as a result of the previous injury. Hamstring muscle and tendon-scar volumes were quantified in both limbs for the biceps femoris long head (BFLH), biceps femoris short head (BFSH), the proximal semimembranosus tendon, and the proximal conjoint biceps femoris and semitendinosus tendon. Differences in muscle and tendon volume between limbs were statistically compared between the previously injured and healthy control subjects. Increased low-intensity signal was present along the musculotendon junction adjacent to the site of presumed prior injury for 11 of the 14 subjects, suggestive of persistent scar tissue. The 13 subjects with biceps femoris injuries displayed a significant decrease in BFLH volume (p < 0.01), often accompanied by an increase in BFSH volume. Two of these subjects also presented with fatty infiltration within the previously injured BFLH. The results of this study provide evidence of long-term musculotendon remodeling following a hamstring strain injury. Additionally, many athletes are likely returning to sport with residual atrophy of the BFLH and/or hypertrophy of the BFSH. It is possible that long-term changes in musculotendon structure following injury alters contraction mechanics during functional movement, such as running and may contribute to reinjury risk. (orig.)

Long-Term Memory Performance in Adult ADHD.

Science.gov (United States)

Skodzik, Timo; Holling, Heinz; Pedersen, Anya

2017-02-01

Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

Gamma knife radiosurgery in patients with persistent acromegaly or Cushing's disease: long-term risk of hypopituitarism.

Science.gov (United States)

Cohen-Inbar, Or; Ramesh, Arjun; Xu, Zhiyuan; Vance, Mary Lee; Schlesinger, David; Sheehan, Jason P

2016-04-01

For patient with a recurrent or residual acromegaly or Cushing's disease (CD) after resection, gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow-up has hampered understanding of the latent risks of hypopituitarism in patients with acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for acromegaly or CD. From a prospectively created, IRB-approved database, we identified all patients with acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow-up of 60 months were included. The median follow-up is 159·5 months (60·1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Sixty patients with either acromegaly or CD were included. Median tumour volume at time of GKRS was 1·3 cm(3) (0·3-13·4), and median margin dose was 25 Gy (6-30). GKRS-induced new pituitary deficiency occurred in 58·3% (n = 35) of patients. Growth hormone deficiency was most common (28·3%, n = 17). The actuarial overall rates of hypopituitarism at 3, 5 and 10 years were 10%, 21·7% and 53·3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumour was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (P = 0·018). Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS. © 2015 John Wiley & Sons Ltd.

Long-term socioeconomic impacts of flooding in Bangladesh

Science.gov (United States)

Jina, A.

2013-05-01

Natural disasters lead to myriad negative impacts upon society, causing loss of life, property, and income. Among disasters, floods annually affect the most people, and lead to widespread negative outcomes, particularly in developing countries. While immediate effects of disasters are readily observed, long-term socioeconomic effects have received little attention. Recent work in development economics finds that environmental exposure in early life can have negative impacts upon later outcomes in health, education, and labor markets. Such research is problematic for disasters, however, as objective measurements of hazard exposure are difficult to obtain. This study develops a remote sensing method to detect flooding in Bangladesh, one of the most flood-prone countries, using MODIS 8-day composite data. This approach addresses one of the main problems in the literature on the social impacts of disasters by deriving an objective measure rather than using self-reported damages. Flood data from 2000-2012 is matched to geolocated social surveys conducted by the Bangladesh government to identify impacts of exposure to floods at critical periods of life. While flooding is noted to be a natural and important part of ecosystem functioning in Bangladesh, we aim to understand the impacts of a flood of greater than normal magnitude or abnormal timing to identify the effects on human capital formation. We find that an increase in flooding of one standard deviation (SD) above the mean in the birth month leads to a 3% increase in stunting (2 SD below cohort height). This has implications for physical and cognitive development, shown elsewhere to persist to adulthood. We find that children from households that are exposed to floods while in elementary school are more likely to drop out. Other impacts will be identified in the course of this research. The stated impacts suggest that the long-term health and economic fortunes of the rural poor in Bangladesh are significantly

Long Term Storage of cytogenetic changes in liquidators of Chernobyl

International Nuclear Information System (INIS)

Karpov, V. B.

2004-01-01

At present chromosome aberration analysis in lymphocytes as well as micronucleus assay are most reliable methods of bio indication of radiation effects. The problem of persistent of cytogenetic changes during the long term after exposure is very important. The cytogenetic studies of liquidators residents of St. Petersburg and region revealed that the average chromosome aberration rate 4-5 years after the accident constitutes 4.94±0.38, number of aberrant cells was 4.82±0.36, dicentrics -0.23±0.10 per 100 cells, micronucleus number -46.1±2.1 per 100 cells that is significantly higher than in control group. dispersion analysis confirms the reported level of external exposure effects on chromosome aberration rate (?=0.04) in this group of liquidators. In 73 persons from the group of high risk participants of nuclear tests, nuclear submarine personnel 8-45 years after average number of chromosome aberrations was 6.5±0.32; dicentrics - 0.64±0.10, centric rings- 0.04±0.02 per 100 cells, for micronuclei -51.4±2.82 per thousand cells, that is significantly higher than in control group (p<0.01). In 45.2% cases the aberration markers (disentrics and centric rings) were found. The late cytogenetic effects were observed after decades and possibility to use these indicators for long term diagnosis is now under consideration. (Author)

A Long-term Plan for Kalk

DEFF Research Database (Denmark)

2017-01-01

In this case, the author demonstrates together with the owner-manager of KALK A/S, Mr Rasmus Jorgensen, how to use the Family Business Map to frame a constructive discussion about long-term planning. The Family Business Map is a tool for long-term planning in family firms developed by Professor...

Virtual Models of Long-Term Care

Science.gov (United States)

Phenice, Lillian A.; Griffore, Robert J.

2012-01-01

Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

Immunoregulatory T Cells May Be Involved in Preserving CD4 T Cell Counts in HIV-Infected Long-Term Nonprogressors and Controllers

DEFF Research Database (Denmark)

Gaardbo, Julie C; Ronit, Andreas; Hartling, Hans J

2014-01-01

BACKGROUND: HIV-infected controllers control viral replication and maintain normal CD4 T cell counts. Long-term nonprogressors (LTNPs) also maintain normal CD4 T cell counts but have ongoing viral replication. We hypothesized that immunoregulatory mechanisms are involved in preserved CD4 T cell...... of patients and controls. However, both ECs and LTNPs displayed a large proportion of activated Tregs suggesting immunoregulatory mechanisms to be involved in preserving CD4 T cell counts in HIV-infected nonprogressors....... counts in controllers and in LTNPs. METHODS: Twenty HIV-infected viremic controllers, 5 elite controllers (ECs), and 14 LTNPs were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Regulatory T cells (Tregs), Treg subpopulations, CD161+Th17...

Sleep facilitates long-term face adaptation

OpenAIRE

Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

2013-01-01

Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted imag...

Natural analogs of the long-term performance of engineered covers

International Nuclear Information System (INIS)

Waugh, W.J.; Petersen, K.L.; Link, S.O.; Bjornstad, B.N.; Gee, G.W.

1994-01-01

The unprecedented legislative demand that in-situ waste-disposal facilities effectively persist indefinitely requires a performance assessment approach that exceeds standard engineering practices and incorporates possible long-term changes in site hydrology, geology, and ecology. Even in relatively arid regions, over time, buried waste will be vulnerable to transport via rainwater percolation, gas diffusion, erosion, and intrusion by plant roots, burrowing animals, and humans. Standard models and field tests of engineered covers designed to impede these pathways implicitly and erroneously assume that initial conditions of many key determinants will persist indefinitely. Evidence from natural, archaeological, and engineered analogs is needed (1) to identify and understand emergent system attributes that cannot be captured with computer models or short-term experiments, and (2) to develop modeling and field tests that reasonably bound possible future changes in waste-site environments. Analogs of local responses to future global climate change exist as proxy ecological and archaeological records of similar paleoclimates. Future pedogenic influences can be inferred form measurements of key soil properties in natural and archaeological soil profiles analogous to engineered covers. Many cover designs depend on water extraction by plants. Influences of vegetation change can be inferred by measuring water extraction parameters in plant communities representing successional chronosequences. Habitats similar to those created on waste sites provide evidence of the potential for biological intrusion. Recent and ancient man-made structures provide evidence of the future stability of waste-site covers and of features that may discourage human intrusion. 108 refs., 4 figs

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

Science.gov (United States)

Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

Keeping it quiet: chromatin control of gammaherpesvirus latency.

Science.gov (United States)

Lieberman, Paul M

2013-12-01

The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) establish long-term latent infections associated with diverse human cancers. Viral oncogenesis depends on the ability of the latent viral genome to persist in host nuclei as episomes that express a restricted yet dynamic pattern of viral genes. Multiple epigenetic events control viral episome generation and maintenance. This Review highlights some of the recent findings on the role of chromatin assembly, histone and DNA modifications, and higher-order chromosome structures that enable gammaherpesviruses to establish stable latent infections that mediate viral pathogenesis.

Efficacy of long-term omalizumab therapy in patients with severe asthma.

Science.gov (United States)

Saji, Junko; Yamamoto, Takahito; Arai, Motonaka; Mineshita, Masamichi; Miyazawa, Teruomi

2017-03-01

The efficacy of omalizumab, an anti-immunoglobulin E (IgE) antibody, has been studied in patients with severe bronchial asthma. We conducted a study to evaluate, on the basis of both objective and subjective measures, the efficacy of omalizumab as a long-term therapy in patients with severe and persistent asthma. Omalizumab was administered subcutaneously every two or four weeks. The results of pulmonary function tests, Asthma Control Test (ACT) and Asthma Health Questionnaire (AHQ)-33 scores, the dosage of methylprednisolone during the 12-month treatment period, and the number of emergency visits prior to the start of treatment with omalizumab were compared in patients pre- and post-treatment with omalizumab. Fourteen patients were enrolled in the study between June 2010 and February 2012. Ten patients completed the study. With omalizumab treatment, there was no improvement in lung function; however, the number of emergency visits (19.3 before treatment vs. 1.2 after treatment, p=0.020) and the dosage of methylprednisolone (871.5mg before treatment vs. 119.0mg after treatment, p=0.046) decreased significantly. ACT and AHQ-33 scores at 16 weeks after treatment were significantly better than baseline scores. Four patients continued treatment with omalizumab for four years, and a reduction in their corticosteroid usage was noted. Long-term omalizumab therapy in our patients was found to significantly reduce corticosteroid usage and the number of emergency visits. Long-term omalizumab therapy was effective and might have potential to reduce the frequency of asthma exacerbations. The trial has not been registered because it is not an intervention study. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

WOMEN'S AGE AT FIRST MARRIAGE AND LONG-TERM ECONOMIC EMPOWERMENT IN EGYPT.

Science.gov (United States)

Yount, Kathryn M; Crandall, AliceAnn; Cheong, Yuk Fai

2018-02-01

Sustainable Development Goal (SDG) 5 calls on nations to promote gender equality and to empower women and girls. SDG5 also recognizes the value of women's economic empowerment, entailing equal rights to economic resources and full participation at all levels in economic decisions. Also according to SDG5, eliminating harmful practices-such as child marriage before age 18-is a prerequisite for women's economic empowerment. Using national data for 4,129 married women 15-43 years who took part in the Egypt Labor Market Panel Survey (ELMPS 1998-2012), we performed autoregressive, cross-lagged panel analyses to assess whether women's first marriage in adulthood (at 18 years or older, as reported in 2006), was positively associated with their long-term post-marital economic empowerment, measured as their engagement in market work and latent family economic agency in 2012. Women's first marriage in adulthood had positive unadjusted associations with their market work and family economic agency in 2012. These associations persisted after accounting for market work and family economic agency in 2006, pre-marital resources for empowerment, and cumulative fertility. Policies to discourage child marriage may show promise to enhance women's long-term post-marital economic empowerment.

Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress.

Science.gov (United States)

Maggio, Nicola; Segal, Menahem

2011-04-15

The ventral hippocampus (VH) was recently shown to express lower magnitude long-term potentiation (LTP) compared with the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. Stressful experience in adolescence has been shown to produce long-lasting effects on animal behavior and on ability to express LTP/long-term depression (LTD) of reactivity to afferent stimulation in the adult. We are interested in possible interactions between juvenile and adult stress in their effects of adult plasticity. We studied the effects of a composite juvenile (28-30 days) stress, followed by a reminder stressful experience in the young adult (60 days) rat, on the ability to produce LTP and LTD in CA1 region of slices of the VH and DH. Juvenile or adult stress produced a transient decrease in ability to express LTP in DH and a parallel increase in LTP in VH. Stress in the young adult after juvenile stress produced a striking prolongation of the DH/VH disparity with respect to the ability to express both LTP and LTD into the adulthood of the rat. These results have important implications for the impact of juvenile stress on adult neuronal plasticity and on the understanding the functions of the different sectors of the hippocampus. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Long-term homelessness in men with a psychosis: Limitation of services.

Science.gov (United States)

Burns, Adam; Robins, Alan; Hodge, Mark; Holmes, Alex

2009-04-01

A proportion of persistently homeless men with psychosis are unable to function in the community, despite intensive outreach. The present study aimed to (i) develop a method to measure the number of homeless clients with a psychosis who are unable to maintain basic levels of function, despite the application of intensive community treatment; and (ii) determine if the proportion of these men had increased in an Australian inner urban setting over a 5-year period. Criteria were developed and validated to define this group. A review of records of clients engaged in homeless settings was conducted in order to compare the proportion of men with these features in 2000 and 2005. In 2005, 23% met the criterion of long-term homelessness with poor function, despite intensive outreach, as compared with 17% in 2000 (P = 0.62). The 2005 cohort was more likely to have attempted intensive community psychiatric treatment (P = 0.04). We conclude that a proportion of homeless men with a psychosis in Australia do not achieve basic function, despite access to intensive outreach. The proportion of these men did not change between 2000 and 2005. These men require additional specialized services, including access to long-term supported housing.

Reforming Management of Behavior Symptoms and Psychiatric Conditions in Long-Term Care Facilities: A Different Perspective.

Science.gov (United States)

Levenson, Steven A; Desai, Abhilash K

2017-04-01

Despite much attention including national initiatives, concerns remain about the approaches to managing behavior symptoms and psychiatric conditions across all settings, including in long-term care settings such as nursing homes and assisted living facilities. One key reason why problems persist is because most efforts to "reform" and "correct" the situation have failed to explore or address root causes and instead have promoted inadequate piecemeal "solutions." Further improvement requires jumping off the bandwagon and rethinking the entire issue, including recognizing and applying key concepts of clinical reasoning and the care delivery process to every situation. The huge negative impact of cognitive biases and rote approaches on related clinical problem solving and decision making and patient outcomes also must be addressed. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Hepatitis C Virus: Viral Quasispecies and Genotypes.

Science.gov (United States)

Tsukiyama-Kohara, Kyoko; Kohara, Michinori

2017-12-22

Hepatitis C virus (HCV) mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs), which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.

Long-Term Stewardship Baseline Report and Transition Guidance

Energy Technology Data Exchange (ETDEWEB)

Kristofferson, Keith

2001-11-01

Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

Niches for the Long-Term Maintenance of Tissue-Resident Memory T Cells

Science.gov (United States)

Takamura, Shiki

2018-01-01

Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. CD4+ TRM cells typically localize below the epithelial layers, such as below the basement membrane, and cluster in lymphoid structures designed to optimize interactions with antigen-presenting cells upon reinfection. A key feature of TRM populations is their ability to be maintained in barrier tissues for prolonged periods of time. For example, skin CD8+ TRM cells displace epidermal niches originally occupied by γδ T cells, thereby enabling their stable persistence for years. It is also clear that the long-term maintenance of TRM cells in different microenvironments is dependent on multiple tissue-specific survival cues, although the specific details are poorly understood. However, not all TRM persist over the long term. Recently, we identified a new spatial niche for the maintenance of CD8+ TRM cells in the lung, which is created at the site of tissue regeneration after injury [termed repair-associated memory depots (RAMD)]. The short-lived nature of RAMD potentially explains the short lifespans of CD8+ TRM cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of TRM cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Science.gov (United States)

Crucian, B. E.; Mehta, S.; Stowe, R. P.; Uchakin, P.; Quiriarte, H.; Pierson, D.; Sams, C. F.

2011-01-01

This poster presentation reviews a study that is designed to address immune system dysregulation and the risk to crewmembers in long duration exploration class missions. This study will address these objectives: (1) Determine the status of adaptive immunity physiological stress, viral immunity, latent herpesvirus reactivation in astronauts during 6 month missions to the International Space Station; (2) determine the clinical risk related to immune dysregulation for exploration class spaceflight; and (3) determine an appropriate monitoring strategy for spaceflight-associated immune dysfunction that could be used for the evaluation of countermeasures. The study anticipates 17 subjects, and for this presentation, (midpoint study data) 10 subjects are reviewed.

Long-Term Prognosis of Plantar Fasciitis

DEFF Research Database (Denmark)

Hansen, Liselotte; Krogh, Thøger Persson; Ellingsen, Torkell

2018-01-01

, exercise-induced symptoms, bilateral heel pain, fascia thickness, and presence of a heel spur) could predict long-term outcomes, (3) to assess the long-term ultrasound (US) development in the fascia, and (4) to assess whether US-guided corticosteroid injections induce atrophy of the heel fat pad. Study....... The risk was significantly greater for women (P heel...... regardless of symptoms and had no impact on prognosis, and neither did the presence of a heel spur. Only 24% of asymptomatic patients had a normal fascia on US at long-term follow-up. A US-guided corticosteroid injection did not cause atrophy of the heel fat pad. Our observational study did not allow us...

Affective Load and Engagement in Second Life: Experiencing Urgent, Persistent, and Long-Term Information Needs

Science.gov (United States)

Nahl, Diane

2010-01-01

New users of virtual environments face a steep learning curve, requiring persistence and determination to overcome challenges experienced while acclimatizing to the demands of avatar-mediated behavior. Concurrent structured self-reports can be used to monitor the personal affective and cognitive struggles involved in virtual world adaptation to…

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

Science.gov (United States)

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

2011-01-01

It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes. PMID:21960964

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement.

Science.gov (United States)

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

2011-01-01

It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.

Short-term versus long-term contracting for uranium enrichment services

International Nuclear Information System (INIS)

Rudy, G.P.

1990-01-01

The US Department of Energy (US DOE) is the world's largest and most experienced supplier of uranium enrichment services. Through the late 1970s and early 1980s, emerging market forces transformed what was once a monopoly into a highly competitive industry. In the early 1980's the DOE lost market share. But as we enter the 1990s, new market forces have emerged. The US DOE believes a responsible balance between long-term and short-term contracting will be the key to success and the key to assuring the long-term health and reliability of the nuclear fuel industry. The US DOE intends to be in this nuclear business for a long time and will continue to offer reliable and responsive services second to none

Simultaneous above and below approach to giant pituitary adenomas: surgical strategies and long-term follow-up

Science.gov (United States)

D’Ambrosio, Anthony L.; Grobelny, Bartosz T.; Freda, Pamela U.; Wardlaw, Sharon; Bruce, Jeffrey N.

2012-01-01

Introduction Giant pituitary adenomas of excessive size, fibrous consistency or unfavorable geometric configuration may be unresectable through conventional operative approaches. We present our select case series for operative resection and long-term follow-up for these unusual tumors, employing both a staged procedure and a combined transsphenoidal-transcranial above and below approach. Method A retrospective chart review was performed on patients operated via the staged, and combined approaches by the senior author (J.N·B.). Pre-operative characteristics and postoperative outcomes were reviewed. A detailed description of the operative technique and perioperative management is provided. Results Between 1993 and 1996, two patients harboring giant pituitary adenomas underwent an intentionally staged resection, and between 1997 and 2006, nine patients harboring giant pituitary adenomas underwent surgery via a single-stage above and below approach. Nine patients (82%) presented with non-secreting adenomas and two patients (18%) presented with prolactinomas refractory to medical management. Gross total resection was achieved in six patients (55%), near total resection in 1 (9%), and subtotal removal in 4 (36%). Seven patients (64%) experienced visual improvement postoperatively and no major complications occurred. Long-term follow-up averaged 51.6 months. Panhypopituitarism was observed in four patients, partial hypopituitarism in four, persistent DI in two, and persistent SIADH in one. Conclusions The addition of a transcranial component to the transsphenoidal approach offers additional visualization of critical neurovascular structures during giant pituitary adenoma resection. Complications rates are similar to other series in which complex pituitary adenomas are resected by other means. The above and below approach is both safe and effective and the immediate and long-term advantages of a single-stage approach justify its utility in this select group of patients

Long-Term Dynamics of Autonomous Fractional Differential Equations

Science.gov (United States)

Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

Science.gov (United States)

Older Women's League, Washington, DC.

Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

Tick exposure and extreme climate events impact survival and threaten the persistence of a long-lived lizard.

Science.gov (United States)

Jones, Alice R; Bull, C Michael; Brook, Barry W; Wells, Konstans; Pollock, Kenneth H; Fordham, Damien A

2016-03-01

Assessing the impacts of multiple, often synergistic, stressors on the population dynamics of long-lived species is becoming increasingly important due to recent and future global change. Tiliqua rugosa (sleepy lizard) is a long-lived skink (>30 years) that is adapted to survive in semi-arid environments with varying levels of parasite exposure and highly seasonal food availability. We used an exhaustive database of 30 years of capture-mark-recapture records to quantify the impacts of both parasite exposure and environmental conditions on the lizard's survival rates and long-term population dynamics. Lizard abundance was relatively stable throughout the study period; however, there were changing patterns in adult and juvenile apparent survival rates, driven by spatial and temporal variation in levels of tick exposure and temporal variation in environmental conditions. Extreme weather events during the winter and spring seasons were identified as important environmental drivers of survival. Climate models predict a dramatic increase in the frequency of extreme hot and dry winter and spring seasons in our South Australian study region; from a contemporary probability of 0.17 up to 0.47-0.83 in 2080 depending on the emissions scenario. Our stochastic population model projections showed that these future climatic conditions will induce a decline in the abundance of this long-lived reptile of up to 67% within 30 years from 2080, under worst case scenario modelling. The results have broad implications for future work investigating the drivers of population dynamics and persistence. We highlight the importance of long-term data sets and accounting for synergistic impacts between multiple stressors. We show that predicted increases in the frequency of extreme climate events have the potential to considerably and negatively influence a long-lived species, which might previously have been assumed to be resilient to environmental perturbations. © 2015 The Authors. Journal of

Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

Science.gov (United States)

Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

2016-06-01

Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

Succesful therapy of viral leukemia by transplantation of histocompatibly unmatched marrow

International Nuclear Information System (INIS)

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

1978-01-01

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

Hysteroscopic Endometrial Resection Versus Laparoscopic Supracervical Hysterectomy for Abnormal Uterine Bleeding: Long-term Follow-up of a Randomized Trial.

Science.gov (United States)

Zupi, Errico; Centini, Gabriele; Lazzeri, Lucia; Finco, Andrea; Exacoustos, Caterina; Afors, Karolina; Zullo, Fulvio; Petraglia, Felice

2015-01-01

To compare long-term efficacy of laparoscopic supracervical hysterectomy (LSH) and hysteroscopic endometrial ablation (HEA) in treating persistent abnormal uterine bleeding. Canadian Task Force II-2. University hospital. One hundred fifty-three women treated for abnormal uterine bleeding by LSH or HEA. Long-term follow-up assessment of reintervention rate and quality of life (QoL) using the Quality Metric's Health Survey Short Form 12. This study is the long-term follow-up of a randomized control trial conducted in 2003 comparing LSH and HEA in terms of reoperation rate and QoL. Starting from November 2010 all patients included in the first trial were invited to participate in this study and clinically evaluated through vaginal examination and transvaginal ultrasound. After a mean follow-up of 14.4 years, 29% of patients (20/71) treated with HEA underwent further surgery, whereas no patients after LSH had symptom recurrence. The reintervention rate was significantly higher in the HEA group (p abnormal uterine bleeding when compared with HEA. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

Long term wet spent nuclear fuel storage

International Nuclear Information System (INIS)

1987-04-01

The meeting showed that there is continuing confidence in the use of wet storage for spent nuclear fuel and that long-term wet storage of fuel clad in zirconium alloys can be readily achieved. The importance of maintaining good water chemistry has been identified. The long-term wet storage behaviour of sensitized stainless steel clad fuel involves, as yet, some uncertainties. However, great reliance will be placed on long-term wet storage of spent fuel into the future. The following topics were treated to some extent: Oxidation of the external surface of fuel clad, rod consolidation, radiation protection, optimum methods of treating spent fuel storage water, physical radiation effects, and the behaviour of spent fuel assemblies of long-term wet storage conditions. A number of papers on national experience are included

Long-Term Collections

CERN Multimedia

Staff Association

2016-01-01

45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

Long-Term Collection

CERN Multimedia

Staff Association

2016-01-01

Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

Persistent Epstein-Barr viral load in Epstein-Barr viral naïve pediatric heart transplant recipients: Risk of late-onset post-transplant lymphoproliferative disease.

Science.gov (United States)

Das, Bibhuti; Morrow, Robert; Huang, Rong; Fixler, David

2016-12-24

To examine the risk of late-onset post-transplant lymphoproliferative disorder (PTLD) in the presence of persisting high Epstein-Barr virus (EBV) in EBV naïve pediatric heart transplant (HT) recipients. A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. PTLD was diagnosed in 8 out of 145 patients (5.5%); 6/91 (6.5%) in those who were EBV seropositive and 2/54 (3.7%) in the EBV naïve group at the time of HT ( P = 0.71). We found 32/145 (22%) patients with persistently high EBV load during continuing follow-up; 20/91 (22%) in EBV seropositive group vs 12/54 (22%) in EBV naïve group ( P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant ( P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15% (3/20) of patients with high EBV vs 4.2% (3/71) of patients with low or undetectable EBV load ( P = 0.14) whereas in EBV naïve patients 8.3% (1/12) of those with high EBV load and 2.3% (1/42) with low or undetectable EBV load ( P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up (4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort ( P = 0.005). At least one episode of acute rejection occurred in 72% (23/32) of patients with high EBV vs 36% (41/113) patients with low or undetectable EBV after HT ( P < 0.05). There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in

Persistence of Change: Fume Hood Campaign Lessons

Science.gov (United States)

Feder, Elah; Robinson, Jennifer; Wakefield, Sarah

2012-01-01

Purpose: Sustainability initiatives typically operate for a limited time period, but it is often unclear whether they have lasting effects. The purpose of this paper is to examine a laboratory fume hood campaign, in order to identify factors that might contribute or detract from long-term change persistence. Design/methodology/approach: The…

Changing incentives for long-term gas contracts

International Nuclear Information System (INIS)

Bohi, D.R.

1992-01-01

There is much concern about the absence of long-term gas contracts with fixed price and quantity conditions, which until recent years was the standard way of doing business in the gas industry. These types of contracts performed a valuable service in the development of the gas industry, and there comparative absence today is sometimes thought to be one reason for the current malaise in the industry. One hears the argument that there must be some kind of 'market failure' that prevents buyers and sellers from entering into these long term arrangements, and recent changes in state and federal regulations are often cited as the cause of the problem. The purpose of the author's remarks is to argue that what is taken as a breakdown in the market may be simply a reaction to a decline in economic incentives to enter into long-term contracts with rigid price and quantity terms. This is, in other words, simply one more aspect of change in the gas business that Frank Heintz referred to in his opening remarks this morning. The author starts by giving a brief description of the motives for engaging in long-term contracts, and then describes how incentives to use long-term contracts have declined for both gas buyers and gas sellers. He concludes that the decline in the use of long-term contracts is not cause for regulatory concern, but a result of the continuing transformation of the gas business to one that more closely resembles other commodity markets

Energy in 2010 - 2020. Long term challenges; Energie 2010-2020. Les defis du long terme

Energy Technology Data Exchange (ETDEWEB)

Dessus, Benjamin [ed.] [Centre National de la Recherche Scientifique (CNRS), 75 - Paris (France)

2000-02-02

This report presents the results of a workshop intending to anticipate the long term challenges, to guide better the short term power options, to understand the available political, economical and technical assumptions for the prospective world situation, to give some strategic hints on the necessary transition. Indeed, the difficult issue which the workshop tried to tackle was how should we prepare to reveal the energetic challenge of the development of the eight to ten billion inhabitants of our Planet in the next century without jeopardizing its existence. The energetic problems, a hardcore of the international preoccupation of both growth and environment, as it was recently evidenced by the climatic conference in Kyoto, have ever been the object of a particular attention on the part of General Commissariat of Plan. Thus, the commission 'Energy in 2010 - 2020' has been instituted in April 1996 in order to update the works done in 1990 - 1991 by the commission 'Energy 2010'. Soon it occurred to this new commission the task of illuminating its works by a long term (2050 - 2100) world prospective analysis of the challenges and problems linked to energy, growth and environment. In conclusion, this document tried to find answers to questions like: - which are the risks the energy consumption augmentation entail? - can we control them by appropriate urbanism and transport policies or technological innovation?. Four options for immediate action are suggested: - the energy efficiency should become a priority objective of policies; -coping with the long term challenges requires acting at present; - building the transition between governmental leadership and market; - taking profit of all the possible synergies between short and long term planning.

Opening remarks for a panel discussion on short-term vs long-term procurement

International Nuclear Information System (INIS)

Courtenay, R.H.

1990-01-01

Long-term contracting in the late 1970's and early 1980's is blamed for some of the inequities that plague the uranium industry today. Utilities are obliged to pay prices far above prevailing levels and relatively low cost producers are forced to shut down while watching less efficient suppliers stay in business thanks to their long term supply agreements. Furthermore, it is argued that long-term contracts have contributed to supply instability by forcing the buildup of surplus inventories and by supporting excess incremental production by suppliers who have a baseload of long-term contracts. The depressed prices resulting from this oversupply are in turn jeopardizing future resource development and damaging supply reliability. In summary, the author's argument is that supply reliability will be greatly enhanced by the assurance of adequate primary supply from traditional sources such as Canada. This will not happen without long-term contracts. This conclusion may not be expected coming from a representative of Canada's largest uranium producer. But the final comment is less self serving. Many of the critics of long term contracts apparently expect a continuing and plentiful supply of East Bloc uranium to the spot market. A further question is to what extent East Bloc suppliers will eventually require long-term contracts in order to maintain production facilitates in economies that are no longer centrally planned, and where there is open competition for capital. Ultimately, reliability of supply from the non-traditional suppliers may also depend on long-term contracts

Long-term outcomes of fertility-sparing treatment of atypical polypoid adenomyoma with medroxyprogesterone acetate.

Science.gov (United States)

Nomura, Hidetaka; Sugiyama, Yuko; Tanigawa, Terumi; Matoda, Maki; Kanao, Hiroyuki; Kondo, Eiji; Takeshima, Nobuhiro

2016-01-01

Our objective was to analyze the long-term oncologic outcomes of fertility-preserving hormonal treatment with medroxyprogesterone acetate (MPA) in patients with APA. In a retrospective chart review, we identified patients with APA who were treated with MPA for fertility preservation at our hospital between 2001 and 2011. Eighteen patients with histologically diagnosed APA were identified. Clinical data including treatment, obstetrical, and oncologic outcomes were recorded. The mean observation period was 77.6 months (median 73.5, range 22-142), and the mean age was 33.6 years. Four patients also developed well-differentiated endometrial carcinoma. After the treatment, 14 patients (77.8 %) achieved either a complete response or partial response. Eight patients experienced recurrence, while four experienced persistent disease. Ten patients (55.6 %) eventually underwent hysterectomy. The median time to hysterectomy was 40.3 months (range 24-68). Nine patients progressed to endometrial cancer, and one experienced persistent APA. Among younger patients (years of age), four out of five patients who were married could have children. Seven patients (38.9 %) showed no evidence of the disease during the observation period (median 60 months, range 22-117 months). No one died because of the disease during the observation period. MPA yields a high response rate in APA, and if only younger patients are considered, a favorable pregnancy rate can be obtained. However, because recurrence rate is high, long-term follow-up under supervision of a trained gynecologic oncologist is required. To confirm MPA's utility, multi-center collaboration would be warranted.

Long-term results of repeated anti-vascular endothelial growth factor therapy in eyes with retinal pigment epithelial tears.

Science.gov (United States)

Moreira, Carlos A; Arana, Luis A; Zago, Rommel J

2013-02-01

To evaluate the long-term results of retinal pigment epithelium tears in eyes treated with repeated anti-vascular endothelial growth factor (VEGF) therapy. Five patients with retinal pigment epithelial tears (without foveal center involvement) after anti-VEGF injection were studied retrospectively. Mean follow-up time was 52 months, with measurements of visual acuity and evaluation of macular findings by angiography and optical coherence tomography during this period. All eyes had a persistent submacular neovascular membrane 30 days after the tear. An anti-VEGF drug was reinjected until the membranes stopped leaking. The mean initial visual acuity immediately after the tear was 20/160, and the mean final visual acuity was 20/60. The number of anti-VEGF reinjections varied from two to eight during the follow-up period. Long-term optical coherence tomography analysis showed reduced fluid and remodeling of the torn retinal pigment epithelium. Long-term visual results with repeated anti-VEGF therapy are not as devastating as suggested previously. Visual acuity and metamorphopsia improve with time as long as the neovascular membrane is inactive. Optical coherence tomography changes in the macular area reflect the visual acuity improvement.

T cell resistance to activation by dendritic cells requires long-term culture in simulated microgravity

Science.gov (United States)

Bradley, Jillian H.; Stein, Rachel; Randolph, Brad; Molina, Emily; Arnold, Jennifer P.; Gregg, Randal K.

2017-11-01

Immune impairment mediated by microgravity threatens the success of space exploration requiring long-duration spaceflight. The cells of most concern, T lymphocytes, coordinate the host response against microbial and cancerous challenges leading to elimination and long-term protection. T cells are activated upon recognition of specific microbial peptides bound on the surface of antigen presenting cells, such as dendritic cells (DC). Subsequently, this engagement results in T cell proliferation and differentiation into effector T cells driven by autocrine interleukin-2 (IL-2) and other cytokines. Finally, the effector T cells acquire the weaponry needed to destroy microbial invaders and tumors. Studies conducted on T cells during spaceflight, or using Earth-based culture systems, have shown reduced production of cytokines, proliferation and effector functions as compared to controls. This may account for the cases of viral reactivation events and opportunistic infections associated with astronauts of numerous missions. This work has largely been based upon the outcome of T cell activation by stimulatory factors that target select T cell signaling pathways rather than the complex, signaling events related to the natural process of antigen presentation by DC. This study tested the response of an ovalbumin peptide-specific T cell line, OT-II TCH, to activation by DC when the T cells were cultured 24-120 h in a simulated microgravity (SMG) environment generated by a rotary cell culture system. Following 72 h culture of T cells in SMG (SMG-T) or control static (Static-T) conditions, IL-2 production by the T cells was reduced in SMG-T cells compared to Static-T cells upon stimulation by phorbol 12-myristate 13-acetate (PMA) and ionomycin. However, when the SMG-T cells were stimulated with DC and peptide, IL-2 was significantly increased compared to Static-T cells. Such enhanced IL-2 production by SMG-T cells peaked at 72 h SMG culture time and decreased thereafter. When

Hepatitis C Virus: Viral Quasispecies and Genotypes

Directory of Open Access Journals (Sweden)

Kyoko Tsukiyama-Kohara

2017-12-01

Full Text Available Hepatitis C virus (HCV mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs, which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.

DEFEAT OF THE CARDIOVASCULAR SYSTEM IN VIRAL INFECTIONS

Directory of Open Access Journals (Sweden)

E. V. Sharipova

2017-01-01

Full Text Available Article is devoted to studying of the submitted epidemiological, clinical, tool, laboratory data on pathology of cardiovascular system at various viral infections. The review is based on results of domestic and foreign researches. At viral infections damage of heart and his carrying-out system perhaps as during the sharp period of a disease, and the period of a convalescence or at the chronic course of virus process. The greatest cardiothrogenism is possessed by enteroviruses, which affect the myocardium in 5–15% of cases. Much attention is paid to herpesviruses, widespread, persistently persistent in the body, as one of the reasons for the development of dilated cardiomyopathy, coronary vasculitis, early atherosclerosis, cardiac rhythm disturbance. Other infections that may affect the cardiovascular system include influenza viruses, adenovirus, poliovirus, Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, hepatitis, mumps, rubella, herpes simplex, varicella, arbovirus, respiratory-syntial virus, yellow fever virus et al. Complications from cardiovascular system can come to light at various age.

Long-term risks of kidney living donation

DEFF Research Database (Denmark)

Maggiore, Umberto; Budde, Klemens; Heemann, Uwe

2017-01-01

Two recent matched cohort studies from the USA and Norway published in 2014 have raised some concerns related to the long-term safety of kidney living donation. Further studies on the long-term risks of living donation have since been published. In this position paper, Developing Education Science...... and Care for Renal Transplantation in European States (DESCARTES) board members critically review the literature in an effort to summarize the current knowledge concerning long-term risks of kidney living donation to help physicians for decision-making purposes and for providing information...... to the prospective live donors. Long-term risk of end-stage renal disease (ESRD) can be partially foreseen by trying to identify donors at risk of developing ‘de novo’ kidney diseases during life post-donation and by predicting lifetime ESRD risk. However, lifetime risk may be difficult to assess in young donors...

Long-term effects of radiation

International Nuclear Information System (INIS)

Smith, J.; Smith, T.

1981-01-01

It is pointed out that sources of long-term damage from radiation are two-fold. People who have been exposed to doses of radiation from initial early fallout but have recovered from the acute effects may still suffer long-term damage from their exposure. Those who have not been exposed to early fallout may be exposed to delayed fallout, the hazards from which are almost exclusively from ingesting strontium, caesium and carbon isotopes present in food; the damage caused is relatively unimportant compared with that caused by the brief doses from initial radiation and early fallout. A brief discussion is presented of the distribution of delayed long-lived isotope fallout, and an outline is sketched of late biological effects, such as malignant disease, cataracts, retarded development, infertility and genetic effects. (U.K.)

Persistence of airline accidents.

Science.gov (United States)

Barros, Carlos Pestana; Faria, Joao Ricardo; Gil-Alana, Luis Alberiko

2010-10-01

This paper expands on air travel accident research by examining the relationship between air travel accidents and airline traffic or volume in the period from 1927-2006. The theoretical model is based on a representative airline company that aims to maximise its profits, and it utilises a fractional integration approach in order to determine whether there is a persistent pattern over time with respect to air accidents and air traffic. Furthermore, the paper analyses how airline accidents are related to traffic using a fractional cointegration approach. It finds that airline accidents are persistent and that a (non-stationary) fractional cointegration relationship exists between total airline accidents and airline passengers, airline miles and airline revenues, with shocks that affect the long-run equilibrium disappearing in the very long term. Moreover, this relation is negative, which might be due to the fact that air travel is becoming safer and there is greater competition in the airline industry. Policy implications are derived for countering accident events, based on competition and regulation. © 2010 The Author(s). Journal compilation © Overseas Development Institute, 2010.

Childhood and adolescent obesity and long-term cognitive consequences during aging.

Science.gov (United States)

Wang, Jun; Freire, Daniel; Knable, Lindsay; Zhao, Wei; Gong, Bing; Mazzola, Paolo; Ho, Lap; Levine, Samara; Pasinetti, Giulio M

2015-04-01

The prevalence of childhood/adolescent obesity and insulin resistance has reached an epidemic level. Obesity's immediate clinical impacts have been extensively studied; however, current clinical evidence underscores the long-term implications. The current study explored the impacts of brief childhood/adolescent obesity and insulin resistance on cognitive function in later life. To mimic childhood/adolescent obesity and insulin resistance, we exposed 9-week-old C57BL/6J mice to a high-fat diet for 15 weeks, after which the mice exhibited diet-induced obesity and insulin resistance. We then put these mice back on a normal low-fat diet, after which the mice exhibited normal body weight and glucose tolerance. However, a spatial memory test in the forms of the Morris water maze (MWM) and contextual fear conditioning at 85 weeks of age showed that these mice had severe deficits in learning and long-term memory consolidation. Mechanistic investigations identified increased expression of histone deacetylases 5, accompanied by reduced expression of brain-derived neurotrophic factor, in the brains 61 weeks after the mice had been off the high-fat diet. Electrophysiology studies showed that hippocampal slices isolated from these mice are more susceptible to synaptic impairments compared with slices isolated from the control mice. We demonstrated that a 15-week occurrence of obesity and insulin resistance during childhood/adolescence induces irreversible epigenetic modifications in the brain that persist following restoration of normal metabolic homeostasis, leading to brain synaptic dysfunction during aging. Our study provides experimental evidence that limited early-life exposure to obesity and insulin resistance may have long-term deleterious consequences in the brain, contributing to the onset/progression of cognitive dysfunction during aging. © 2014 Wiley Periodicals, Inc.

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.

Long-term biases in geomagnetic K and aa indices

Science.gov (United States)

Love, J.J.

2011-01-01

Analysis is made of the geomagnetic-activity aa index and its source K-index data from groups of ground-based observatories in Britain, and Australia, 1868.0-2009.0, solar cycles 11-23. The K data show persistent biases, especially for high (low) K-activity levels at British (Australian) observatories. From examination of multiple subsets of the K data we infer that the biases are not predominantly the result of changes in observatory location, localized induced magnetotelluric currents, changes in magnetometer technology, or the modernization of K-value estimation methods. Instead, the biases appear to be artifacts of the latitude-dependent scaling used to assign K values to particular local levels of geomagnetic activity. The biases are not effectively removed by weighting factors used to estimate aa. We show that long-term averages of the aa index, such as annual averages, are dominated by medium-level geomagnetic activity levels having K values of 3 and 4. ?? 2011 Author(s).

Long-term biases in geomagnetic K and aa indices

Directory of Open Access Journals (Sweden)

J. J. Love

2011-08-01

Full Text Available Analysis is made of the geomagnetic-activity aa index and its source K-index data from groups of ground-based observatories in Britain, and Australia, 1868.0–2009.0, solar cycles 11–23. The K data show persistent biases, especially for high (low K-activity levels at British (Australian observatories. From examination of multiple subsets of the K data we infer that the biases are not predominantly the result of changes in observatory location, localized induced magnetotelluric currents, changes in magnetometer technology, or the modernization of K-value estimation methods. Instead, the biases appear to be artifacts of the latitude-dependent scaling used to assign K values to particular local levels of geomagnetic activity. The biases are not effectively removed by weighting factors used to estimate aa. We show that long-term averages of the aa index, such as annual averages, are dominated by medium-level geomagnetic activity levels having K values of 3 and 4.

Postflood persistence and recolonization of endangered tidewater goby populations

Science.gov (United States)

Lafferty, Kevin D.; Swift, Camm C.; Ambrose, Richard F.

1999-01-01

Before-and-after surveys at several southern California sites indicated that populations of endangered tidewater goby Eucyclogobius newberryi persisted through heavy flooding in 1995. This was contrary to our expectations that flooding might have led to extirpation in some smaller wetlands. There was also no significant change in tidewater goby density before and after the flooding. Several apparent recolonization events coincided with the flood, suggesting that flooding may be important for the long-term persistence of the species.

Experimental infection of pregnant goats with bovine viral diarrhea virus (BVDV)1 or 2

Science.gov (United States)

Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. ...

Influence of long-term Sahaja Yoga meditation practice on emotional processing in the brain: An ERP study.

Science.gov (United States)

Reva, N V; Pavlov, S V; Loktev, K V; Korenyok, V V; Aftanas, L I

2014-12-05

Despite growing interest in meditation as a tool for alternative therapy of stress-related and psychosomatic diseases, brain mechanisms of beneficial influences of meditation practice on health and quality of life are still unclear. We propose that the key point is a persistent change in emotional functioning, specifically the modulation of the early appraisal of motivational significance of events. The main aim was to study the effects of long-term meditation practice on event-related brain potentials (ERPs) during affective picture viewing. ERPs were recorded in 20 long-term Sahaja Yoga meditators and 20 control subjects without prior experience in meditation. The meditators' mid-latency (140-400ms) ERPs were attenuated for both positive and negative pictures (i.e. there were no arousal-related increases in ERP positivity) and this effect was more prominent over the right hemisphere. However, we found no differences in the long latency (400-800ms) responses to emotional images, associated with meditation practice. In addition we found stronger ERP negativity in the time window 200-300ms for meditators compared to the controls, regardless of picture valence. We assume that long-term meditation practice enhances frontal top-down control over fast automatic salience detection, based on amygdala functions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

Science.gov (United States)

Juno, Jennifer A.; van Bockel, David; Kent, Stephen J.; Kelleher, Anthony D.; Zaunders, John J.; Munier, C. Mee Ling

2017-01-01

CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term in vitro cultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections. PMID:28167943

Long-term home care scheduling

DEFF Research Database (Denmark)

Gamst, Mette; Jensen, Thomas Sejr

In several countries, home care is provided for certain citizens living at home. The long-term home care scheduling problem is to generate work plans spanning several days such that a high quality of service is maintained and the overall cost is kept as low as possible. A solution to the problem...... provides detailed information on visits and visit times for each employee on each of the covered days. We propose a branch-and-price algorithm for the long-term home care scheduling problem. The pricing problem generates one-day plans for an employee, and the master problem merges the plans with respect...

Host and viral ecology determine bat rabies seasonality and maintenance

Science.gov (United States)

George, D.B.; Webb, C.T.; Farnsworth, Matthew L.; O'Shea, T.J.; Bowen, R.A.; Smith, D.L.; Stanley, T.R.; Ellison, L.E.; Rupprecht, C.E.

2011-01-01

Rabies is an acute viral infection that is typically fatal. Most rabies modeling has focused on disease dynamics and control within terrestrial mammals (e.g., raccoons and foxes). As such, rabies in bats has been largely neglected until recently. Because bats have been implicated as natural reservoirs for several emerging zoonotic viruses, including SARS-like corona viruses, henipaviruses, and lyssaviruses, understanding how pathogens are maintained within a population becomes vital. Unfortunately, little is known about maintenance mechanisms for any pathogen in bat populations. We present a mathematical model parameterized with unique data from an extensive study of rabies in a Colorado population of big brown bats (Eptesicus fuscus) to elucidate general maintenance mechanisms. We propose that life history patterns of many species of temperate-zone bats, coupled with sufficiently long incubation periods, allows for rabies virus maintenance. Seasonal variability in bat mortality rates, specifically low mortality during hibernation, allows long-term bat population viability. Within viable bat populations, sufficiently long incubation periods allow enough infected individuals to enter hibernation and survive until the following year, and hence avoid an epizootic fadeout of rabies virus. We hypothesize that the slowing effects of hibernation on metabolic and viral activity maintains infected individuals and their pathogens until susceptibles from the annual birth pulse become infected and continue the cycle. This research provides a context to explore similar host ecology and viral dynamics that may explain seasonal patterns and maintenance of other bat-borne diseases.

Analysing long term discursive processes

DEFF Research Database (Denmark)

Horsbøl, Anders

which extend beyond the single interaction, for instance negotiations or planning processes, seems to have played a less important role, with studies such as Iedema 2001 and Wodak 2000 as exceptions. These long term processes, however, are central to the constitution and workings of organizations......What do timescales - the notion that processes take place or can be viewed within a shorter or longer temporal range (Lemke 2005) - mean for the analysis of discourse? What are the methodological consequences of analyzing discourse at different timescales? It may be argued that discourse analysis...... in general has favored either the analysis of short term processes such as interviews, discussions, and lessons, or the analysis of non-processual entities such as (multimodal) texts, arguments, discursive repertoires, and discourses (in a Foucaultian sense). In contrast, analysis of long term processes...

Nuclear Energy, Long Term Requirements

International Nuclear Information System (INIS)

Knapp, V.

2006-01-01

There are serious warnings about depletion of oil and gas and even more serious warnings about dangers of climate change caused by emission of carbon dioxide. Should developed countries be called to replace CO2 emitting energy sources as soon as possible, and the time available may not be longer then few decades, can nuclear energy answer the call and what are the requirements? Assuming optimistic contribution of renewable energy sources, can nuclear energy expand to several times present level in order to replace large part of fossil fuels use? Paper considers intermediate and long-term requirements. Future of nuclear power depends on satisfactory answers on several questions. First group of questions are those important for near and intermediate future. They deal with economics and safety of nuclear power stations in the first place. On the same time scale a generally accepted concept for radioactive waste disposal is also required. All these issues are in the focus of present research and development. Safer and more economical reactors are targets of international efforts in Generation IV and INPRO projects, but aiming further ahead these innovative projects are also addressing issues such as waste reduction and proliferation resistance. However, even assuming successful technical development of these projects, and there is no reason to doubt it, long term and large-scale nuclear power use is thereby not yet secured. If nuclear power is to play an essential role in the long-term future energy production and in reduction of CO2 emission, than several additional questions must be replied. These questions will deal with long-term nuclear fuel sufficiency, with necessary contribution of nuclear power in sectors of transport and industrial processes and with nuclear proliferation safety. This last issue is more political then technical, thus sometimes neglected by nuclear engineers, yet it will have essential role for the long-term prospects of nuclear power. The

Erythropoietin enhances hippocampal long-term potentiation and memory

Directory of Open Access Journals (Sweden)

El-Kordi Ahmed

2008-09-01

Full Text Available Abstract Background Erythropoietin (EPO improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity. Results We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP, a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses. Conclusion We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.

Long term persistence of clonal malaria parasite Plasmodium falciparum lineages in the Colombian Pacific region.

Science.gov (United States)

Echeverry, Diego F; Nair, Shalini; Osorio, Lyda; Menon, Sanjay; Murillo, Claribel; Anderson, Tim J C

2013-01-07

Resistance to chloroquine and antifolate drugs has evolved independently in South America, suggesting that genotype - phenotype studies aimed at understanding the genetic basis of resistance to these and other drugs should be conducted in this continent. This research was conducted to better understand the population structure of Colombian Plasmodium falciparum in preparation for such studies. A set of 384 SNPs were genotyped in blood spot DNA samples from 447 P. falciparum infected subjects collected over a ten year period from four provinces of the Colombian Pacific coast to evaluate clonality, population structure and linkage disequilibrium (LD). Most infections (81%) contained a single predominant clone. These clustered into 136 multilocus genotypes (MLGs), with 32% of MLGs recovered from multiple (2 - 28) independent subjects. We observed extremely low genotypic richness (R = 0.42) and long persistence of MLGs through time (median = 537 days, range = 1 - 2,997 days). There was a high probability (>5%) of sampling parasites from the same MLG in different subjects within 28 days, suggesting caution is needed when using genotyping methods to assess treatment success in clinical drug trials. Panmixia was rejected as four well differentiated subpopulations (FST = 0.084 - 0.279) were identified. These occurred sympatrically but varied in frequency within the four provinces. Linkage disequilibrium (LD) decayed more rapidly (r2 = 0.17 for markers Colombian populations have several advantages for association studies, because multiple clone infections are uncommon and LD decays over the scale of one or a few genes. However, the extensive population structure and low genotype richness will need to be accounted for when designing and analyzing association studies.

What are the differences between long-term, short-term, and working memory?

OpenAIRE

Cowan, Nelson

2008-01-01

In the recent literature there has been considerable confusion about the three types of memory: long-term, short-term, and working memory. This chapter strives to reduce that confusion and makes up-to-date assessments of these types of memory. Long- and short-term memory could differ in two fundamental ways, with only short-term memory demonstrating (1) temporal decay and (2) chunk capacity limits. Both properties of short-term memory are still controversial but the current literature is rath...

Radiological and clinical predictors of long-term outcome in rotator cuff calcific tendinitis.

Science.gov (United States)

de Witte, Pieter Bas; van Adrichem, Raymond A; Selten, Jasmijn W; Nagels, Jochem; Reijnierse, M; Nelissen, Rob G H H

2016-10-01

Knowledge on the epidemiology and long-term course of rotator cuff calcific tendinitis (RCCT) is scarce. We assessed demographics, radiological characteristics, and their association with long-term outcomes in a large patient group. Baseline demographics, radiological characteristics and treatment were recorded in 342 patients. Interobserver agreement of radiological measures was analyzed. Long-term outcome was evaluated with questionnaires (WORC, DASH). The association of baseline characteristics with outcome was assessed. Mean age was 49.0 (SD = 10.0), and 59.5 % were female. The dominant arm was affected in 66.0 %, and 21.3 % had bilateral disease. Calcifications were on average 18.7 mm (SD = 10.1, ICC = 0.84 (p < 0.001)) and located 10.1 mm (SD = 11.8) medially to the acromion (ICC = 0.77 (p < 0.001)). Gärtner type I calcifications were found in 32.1 % (Kappa = 0.47 (p < 0.001)). After 14 years (SD = 7.1) of follow-up, median WORC was 72.5 (range, 3.0-100.0; WORC < 60 in 42 %) and median DASH 17.0 (range, 0.0-82.0). Female gender, dominant arm involvement, bilateral disease, longer duration of symptoms, and multiple calcifications were associated with inferior WORC. DASH results were similar. Many subjects have persisting shoulder complaints years after diagnosis, regardless of treatment. Female gender, dominant arm involvement, bilateral disease, longer duration of symptoms, and multiple calcifications were associated with inferior outcome. Radiological measures had moderate-to-good reliability and no prognostic value. • Most RCCT studies report on short-term outcome and/or small patients groups. • In this large, long-term observational study, RCCT appeared to not be self-limiting in many subjects. • Negative prognostic factors included female gender, more calcifications, dominant arm affected, and longer duration of symptoms. • Interobserver agreement of general radiological RCCT measures is

Long-term hearing preservation in vestibular schwannoma

DEFF Research Database (Denmark)

Stangerup, Sven-Eric; Thomsen, Jens; Tos, Mirko

2010-01-01

The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas.......The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas....

Long-Term Patency of Lymphovenous Anastomoses: A Systematic Review.

Science.gov (United States)

Tourani, Saam S; Taylor, G Ian; Ashton, Mark W

2016-08-01

With advancements in technology and microsurgical techniques, lymphovenous anastomosis has become a popular reconstructive procedure in the treatment of chronic lymphedema. However, the long-term patency of these anastomoses is not clear in the literature. A systematic review of the MEDLINE and EMBASE databases was performed to assess the reported long-term patency of lymphovenous anastomoses. A total of eight studies satisfied the inclusion criteria. Pooled data from four similar experiments in normal dogs showed an average long-term (≥5 months) patency of 52 percent. The only experiment in dogs with chronic lymphedema failed to show any long-term patency. The creation of peripheral lymphovenous anastomoses with a moderate long-term patency rate has become technically possible. However, the long-term results in chronic lymphedema are limited.

Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

Directory of Open Access Journals (Sweden)

Peter Moritz Becher

2017-01-01

Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

Long-Term Orientation in Trade

NARCIS (Netherlands)

Hofstede, G.J.; Jonker, C.M.; Verwaart, D.

2008-01-01

Trust does not work in the same way across cultures. This paper presents an agent model of behavior in trade across Hofstedes cultural dimension of long-term vs. short-term orientation. The situation is based on a gaming simulation, the Trust and Tracing game. The paper investigates the

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

Woody debris along an upland chromosequence in boreal Manitoba and its impact on long-term carbon storage

Energy Technology Data Exchange (ETDEWEB)

Manies, K. L.; Harden, J. W. [US Geological Survey, Menlo Park, CA (United States); Bond-Lamberty, B. P. [University of Wisconsin, Dept. of Forest Ecology and Management, Madison, WI (United States); O' Neill, K. P. [USDA Agricultural Research Service, Appalachian Farming Systems Research Center, Beaver, WV (United States)

2005-02-01

The amount of standing dead and downed woody debris along an upland chromosequence was measured in an effort to investigate the role of fire-killed woody debris as a source of soil carbon in black spruce stands in Manitoba. Based on the measurement data and existing primary production values, a mass balance model was used to assess the potential impact of fire-killed wood on long-term carbon storage at this site. Long-term carbon was represented by the amount of carbon stored in deeper soil organic layers, persisting over millenia. Between 10 and 60 per cent of the deep-soil carbon was estimated to have been derived from wood biomass. The actual amount appears to be most affected by fire return interval, decay rate of wood, the amount of net primary production, and the decay rate of the post-fire carbon pool. Although the model was less sensitive to fire consumption rates and to rates at which standing dead wood becomes woody debris, all model runs clearly established that woody debris plays an important role in long-term carbon storage in this area. 53 refs., 4 tabs., 4 figs.

Systemic inflammation combined with neonatal cerebellar haemorrhage aggravates long-term structural and functional outcomes in a mouse model.

Science.gov (United States)

Tremblay, Sophie; Pai, Alex; Richter, Lindsay; Vafaei, Rod; Potluri, Praneetha; Ellegood, Jacob; Lerch, Jason P; Goldowitz, Daniel

2017-11-01

Despite the increased recognition of cerebellar injury in survivors of preterm birth, the neurodevelopmental consequences of isolated cerebellar injury have been largely unexplored and our current understanding of the functional deficits requires further attention in order to translate knowledge to best practices. Preterm infants are exposed to multiple stressors during their postnatal development including perinatal cerebellar haemorrhage (CBH) and postnatal infection, two major risk factors for neurodevelopmental impairments. We developed a translational mouse model of CBH and/or inflammation to measure the short- and long-term outcomes in cerebellar structure and function. Mice exposed to early combined insults of CBH and early inflammatory state (EIS) have a delay in grasping acquisition, neonatal motor deficits and deficient long-term memory. CBH combined with late inflammatory state (LIS) does not induce neonatal motor problems but leads to poor fine motor function and long-term memory deficits at adulthood. Early combined insults result in poor cerebellar growth from postnatal day 15 until adulthood shown by MRI, which are reflected in diminished volumes of cerebellar structures. There are also decreases in volumes of gray matter and hippocampus. Cerebellar microgliosis appears 24h after the combined insults and persists until postnatal day 15 in the cerebellar molecular layer and cerebellar nuclei in association with a disrupted patterning of myelin deposition, a delay of oligodendrocyte maturation and reduced white matter cerebellar volume. Together, these findings reveal poor outcomes in developing brains exposed to combined cerebellar perinatal insults in association with cerebellar hypoplasia, persistence of microgliosis and alterations of cerebellar white matter maturation and growth. Copyright © 2017 Elsevier Inc. All rights reserved.

The laboratory diagnosis of acute viral hepatitis

African Journals Online (AJOL)

defined level and is thus indicative of recent infection as IgM anti-HBc may persist in low titres for a prolonged period. SAMJ. ARTICLES. Detection of HBeAg in the serum is important in the clinical evaluation of a patient with HBV infection as it usually correlates with viral replication, active liver damage and infectivity.3 ...

Long-term effects of childbirth in MS

NARCIS (Netherlands)

D'hooghe, M.B.; Nagels, G.; Uitdehaag, B.M.J.

2010-01-01

Background: The uncertainty about long-term effects of childbirth presents MS patients with dilemmas. Methods: Based on clinical data of 330 female MS patients, the long-term effects of childbirth were analysed, using a cross-sectional study design. Four groups of patients were distinguished: (1)

Long-term assessment of fatigue in patients with culture-confirmed Lyme disease.

Science.gov (United States)

Wormser, Gary P; Weitzner, Erica; McKenna, Donna; Nadelman, Robert B; Scavarda, Carol; Nowakowski, John

2015-02-01

Fatigue is a common symptom with numerous causes. Severe fatigue is thought to be an important manifestation of post-treatment Lyme disease syndrome. The frequency with which severe fatigue occurs as a long-term sequela in prospectively followed patients with Lyme disease is unknown. Patients with culture-confirmed Lyme disease who originally presented with erythema migrans have been evaluated annually in a prospective study to determine their long-term outcome. In 2011-2013, subjects were evaluated for fatigue using an 11-item Fatigue Severity Scale (FSS-11) that has been used in studies of post-treatment Lyme disease syndrome. An FSS-11 score of ≥4.0 is indicative of severe fatigue. A total of 100 subjects were assessed, 52% of whom were male; the mean age was 64.9 years (range, 42-86 years). The mean duration of follow-up was 15.4 years (range, 11-20 years). Nine subjects had severe fatigue but in none as a consequence of Lyme disease. Only 3 subjects were thought to possibly have persistent fatigue from Lyme disease. The FSS-11 value for these 3 individuals was less than 4, averaging 2.27, and none had functional impairment. Severe fatigue was found in 9 patients (9%) with culture-confirmed early Lyme disease at 11 to 20 years after presentation, but was due to causes other than Lyme disease. Fatigue of lesser severity was possibly due to Lyme disease, but was found in only 3% of 100 patients, and therefore is rarely a long-term complication of this infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Atmospheric emissions and long-range transport of persistent organic chemicals

Directory of Open Access Journals (Sweden)

Scheringer M.

2010-12-01

Full Text Available Persistent organic chemicals include several groups of halogenated compounds, such as polychlorinated biphenyls (PCBs, polybrominated diphenylethers (PBDEs, and polyfluorinated carboxylic acids (PFCAs. These chemicals remain for long times (years to decades in the environment and cycle between different media (air, water, sediment, soil, vegetation, etc.. The environmental distribution of this type of chemicals can conveniently be analyzed by multimedia models. Multimedia models consist of a set of coupled mass balance equations for the environmental media considered; they can be set up at various scales from local to global. Two applications of multimedia models to airborne chemicals are discussed in detail: the day-night cycle of PCBs measured in air near the surface, and the atmospheric long-range transport of volatile precursors of PFCAs, formation of PFCAs by oxidation of these precursors, and subsequent deposition of PFCAs to the surface in remote regions such as the Arctic.

Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

Science.gov (United States)

Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

2011-01-01

To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

Using nestling plasma to assess long-term spatial and temporal concentrations of organochlorine compounds in bald eagles within Voyageurs National Park, Minnesota, USA

Science.gov (United States)

H. Tyler Pittman; William W. Bowerman; Leland H. Grim; Teryl G. Grubb; William C. Bridges; Michael R. Wierda

2015-01-01

The bald eagle (Haliaeetus leucocephalus) population at Voyageurs National Park (VNP) provides an opportunity to assess long-term temporal and spatial trends of persistent environmental contaminants. Nestling bald eagle plasma samples collected from 1997 to 2010 were analyzed for polychlorinated biphenyls (PCBs) and organochlorine pesticides. Trends of total PCBs,...

Aberrant cellular immune responses in humans infected persistently with parvovirus B19

DEFF Research Database (Denmark)

Isa, Adiba; Norbeck, Oscar; Hirbod, Taha

2006-01-01

A subset of parvovirus B19 (B19) infected patients retains the infection for years, as defined by detection of B19 DNA in bone marrow. Thus far, analysis of B19-specific humoral immune responses and viral genome variations has not revealed a mechanism for the absent viral clearance. In this study......, ex-vivo cellular immune responses were assessed by enzyme linked immunospot assay mounted against the majority of the translated viral genome. Compared to seropositive healthy individuals, individuals with B19 persistence (2-8 years) showed larger number of responses to the structural proteins (P = 0.......0022), whereas responses to the non-structural protein were of lower magnitude (P = 0.012). These observations provide the first findings of immunological discrepancies between individuals with B19 persistence and healthy individuals, findings that may reflect both failed immunity and antigenic exhaustion....

[Psychosocial issues of long-term cancer survivors].

Science.gov (United States)

Weis, J; Faller, H

2012-04-01

Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

Are long-term bisphosphonate users a reality?

DEFF Research Database (Denmark)

Abrahamsen, B