WorldWideScience

Sample records for sporadic wnv incursions

  1. Experimental infection of Carrion crows (Corvus corone) with two European West Nile virus (WNV) strains.

    Science.gov (United States)

    Dridi, Maha; Vangeluwe, Didier; Lecollinet, Sylvie; van den Berg, Thierry; Lambrecht, Bénédicte

    2013-07-26

    West Nile virus (WNV) has become a wide-spread arbovirus in Europe and the Mediterranean Basin countries. This emerging zoonotic disease disseminated 13 years ago in North America where its impact on animal and public health has been considerable. Although American corvids have been the most reliable avian sentinels for WN surveillance in the United States, there is so far no data available about the susceptibility of their Western European counterparts to WNV. Clinical follow-up and serum, oral swabs and feathers viral RNA load monitoring was herein performed on wild-caught Carrion crows (Corvus corone) experimentally inoculated with two WNV strains, Is98 that was isolated from a stork in Israel where it elicited high rates of avian deaths in 1998, and Fr2000 which was only associated to sporadic equine cases in Camargue, France in 2000. Inoculated crows were sensitive to both WNV infections and, as expected from the available epidemiological data, Is98 induced a higher mortality rate (100% vs. 33%) and a quicker fatal outcome, with higher viral RNA loads detected in the serum, oral swabs and feathers than in the Fr2000 group. Therefore, Carrion crows should also be a target species for WNV surveillance in Western Europe, where reporting for abnormal mortalities could be completed by viral detection in the herein described avian matrices. These experimental findings also emphasize the peculiarity of the European situation where a large spectrum of WNV genetic and pathotypic variants have been so far isolated despite limited WN disease reports in wild birds. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Rapid communication. New incursions of West Nile virus lineage 2 in Italy in 2013: the value of the entomological surveillance as early warning system

    Directory of Open Access Journals (Sweden)

    Mattia Calzolari

    2013-09-01

    Full Text Available West Nile virus (WNV is one of the most serious public health threats that Europe and the Mediterranean countries are currently facing. In Italy, WNV emerged in 1998 and has been circulating since 2008. To tackle its continuous incursions, Italian national and regional institutions set up a surveillance program, which includes the serological screening of sentinel horses, sentinel-chickens and backyard poultry flocks and the surveillance on all equine neurological cases, resident captured and wild dead birds, and vectors. This communication aims to assess the importance of the entomological surveillance program as an early warning system for WNV circulation. In the province of Modena, the circulation of WNV lineage 2 strains was first detected in pools of Culex pipiens on July the 3rd, 42 days prior to the onset of the first 2013 human WNV neuroinvasive case reported in the same province. Similarly in Veneto, WNV was first detected on July 3rd in a pool of Cx. pipiens collected in the province of Venezia. The first human neuroinvasive case in this region occurred in the Rovigo province on July the 24th, seven days after the detection of WNV lineage 2 in a mosquito pool collected in the same province. Up to the end of July 2013, WNV circulation was further detected in several other pools of Cx. pipiens mosquitoes collected in Emilia-Romagna, Veneto and Lombardia. According to the NS3 partial sequence alignments including all recent European and Italian Lineage 2 strains, the new circulating WNV lineage 2 strains share high nt homology with the Hungarian and with the previous lineage 2 strains isolated in Veneto and Sardegna in 2011 and 2012. These data provide a clear and practical demonstration of the relevance of a reliable entomological surveillance program to early detect WNV in Italy.

  3. WNV infection - an emergent vector borne viral infection in Serbia: Current situation

    Directory of Open Access Journals (Sweden)

    Petrović Tamaš

    2015-01-01

    Full Text Available West Nile virus (WNV is a neurovirulent mosquito-borne Flavivirus with zoonotic potential. Virus is maintained in nature in an enzootic transmission cycle between avian hosts and mosquito vectors, but occasionally infects other vertebrates. The infection in horses and humans can be asymptomatic or it can have different clinical manifestations ranging from light febrile diseases to fatal meningoencephalitis. Recently, the number, frequency and severity of outbreaks with neurological consequences for birds, humans and horses have increased dramatically throughout central and south Europe, including Serbia, posing a serious veterinary and public health problem. The emergency of WNV infections in Serbia is described through the current epidemiology situation based on recent data on the incidence of WNV infection among virus natural hosts and vectors; sentinel (horses and other animal species, and in human population. The results of the WNV serology studies conducted on horse blood samples collected in different occasions during the last six years, and the results of the serology studies conducted among other animal species like pigs, wild boars, roe deer and dogs in Serbia are presented and discussed. Also, the results of the first studies on WNV presence in mosquito vectors and in wild birds as virus natural hosts in Serbia are presented and analyzed. In addition, the data on the WNV serology studies conducted in human population in Serbia in the last few years, and the existing data of WNV outbreaks in 2012 and 2013 are included. Regarding the existing knowledge on WNV epidemiology situation, the crucial role of veterinary service in early detection of WNV presence and ongoing national program of WNV surveillance in sentinel animals, mosquitoes and wild birds are discussed.

  4. Computing anticipatory systems with incursion and hyperincursion

    Science.gov (United States)

    Dubois, Daniel M.

    1998-07-01

    An anticipatory system is a system which contains a model of itself and/or of its environment in view of computing its present state as a function of the prediction of the model. With the concepts of incursion and hyperincursion, anticipatory discrete systems can be modelled, simulated and controlled. By definition an incursion, an inclusive or implicit recursion, can be written as: x(t+1)=F[…,x(t-1),x(t),x(t+1),…] where the value of a variable x(t+1) at time t+1 is a function of this variable at past, present and future times. This is an extension of recursion. Hyperincursion is an incursion with multiple solutions. For example, chaos in the Pearl-Verhulst map model: x(t+1)=a.x(t).[1-x(t)] is controlled by the following anticipatory incursive model: x(t+1)=a.x(t).[1-x(t+1)] which corresponds to the differential anticipatory equation: dx(t)/dt=a.x(t).[1-x(t+1)]-x(t). The main part of this paper deals with the discretisation of differential equation systems of linear and non-linear oscillators. The non-linear oscillator is based on the Lotka-Volterra equations model. The discretisation is made by incursion. The incursive discrete equation system gives the same stability condition than the original differential equations without numerical instabilities. The linearisation of the incursive discrete non-linear Lotka-Volterra equation system gives rise to the classical harmonic oscillator. The incursive discretisation of the linear oscillator is similar to define backward and forward discrete derivatives. A generalized complex derivative is then considered and applied to the harmonic oscillator. Non-locality seems to be a property of anticipatory systems. With some mathematical assumption, the Schrödinger quantum equation is derived for a particle in a uniform potential. Finally an hyperincursive system is given in the case of a neural stack memory.

  5. Serological study on WNV presence in horses in Vojvodina after the human outbreak in Serbia in 2012

    Directory of Open Access Journals (Sweden)

    Petrović T.

    2014-01-01

    Full Text Available To establish the presence of West Nile virus (WNV infection in the animal population in Serbia after the human WNV outbreak, the presence of anti-WNV IgG antibodies was examined by commercial ELISA of blood sera samples of 130 horses collected in 2012 from 6 stables and 1 settlement in Vojvodina Province, northern Serbia. During the blood sampling, hibernating mosquitoes in the vicinity of the sampled horses were collected (31 pools from 4 locations and tested for WNV presence by real-time RT-PCR. The presence of anti-WNV antibodies was observed in 49.23% (64/130 horses. Per stable, the percent of seropositive animals ranged from 35% to 64%. All 31 analyzed pools of hibernating mosquitoes tested negative for WNV RNA. The WNV-antibody prevalence of 49.23% obtained in horses during 2012 was much higher than the prevalence (12% found in horses during 2009/2010. These results, including the confirmed seroconversion in eight horses that tested negative in 2010, indicated an intensive WNV circulation during 2012 in Serbia, and the necessity of implementing surveillance programs. [Projekat Ministarstva nauke Republike Srbije, br. TR31084 and III43007

  6. Wolbachia enhances West Nile virus (WNV infection in the mosquito Culex tarsalis.

    Directory of Open Access Journals (Sweden)

    Brittany L Dodson

    2014-07-01

    Full Text Available Novel strategies are required to control mosquitoes and the pathogens they transmit. One attractive approach involves maternally inherited endosymbiotic Wolbachia bacteria. After artificial infection with Wolbachia, many mosquitoes become refractory to infection and transmission of diverse pathogens. We evaluated the effects of Wolbachia (wAlbB strain on infection, dissemination and transmission of West Nile virus (WNV in the naturally uninfected mosquito Culex tarsalis, which is an important WNV vector in North America. After inoculation into adult female mosquitoes, Wolbachia reached high titers and disseminated widely to numerous tissues including the head, thoracic flight muscles, fat body and ovarian follicles. Contrary to other systems, Wolbachia did not inhibit WNV in this mosquito. Rather, WNV infection rate was significantly higher in Wolbachia-infected mosquitoes compared to controls. Quantitative PCR of selected innate immune genes indicated that REL1 (the activator of the antiviral Toll immune pathway was down regulated in Wolbachia-infected relative to control mosquitoes. This is the first observation of Wolbachia-induced enhancement of a human pathogen in mosquitoes, suggesting that caution should be applied before releasing Wolbachia-infected insects as part of a vector-borne disease control program.

  7. Pro-inflammatory cytokines derived from West Nile virus (WNV-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death

    Directory of Open Access Journals (Sweden)

    Nerurkar Vivek R

    2010-10-01

    Full Text Available Abstract Background WNV-associated encephalitis (WNVE is characterized by increased production of pro-inflammatory mediators, glial cells activation and eventual loss of neurons. WNV infection of neurons is rapidly progressive and destructive whereas infection of non-neuronal brain cells is limited. However, the role of neurons and pathological consequences of pro-inflammatory cytokines released as a result of WNV infection is unclear. Therefore, the objective of this study was to examine the role of key cytokines secreted by WNV-infected neurons in mediating neuroinflammatory markers and neuronal death. Methods A transformed human neuroblastoma cell line, SK-N-SH, was infected with WNV at multiplicity of infection (MOI-1 and -5, and WNV replication kinetics and expression profile of key pro-inflammatory cytokines were analyzed by plaque assay, qRT-PCR, and ELISA. Cell death was measured in SK-N-SH cell line in the presence and absence of neutralizing antibodies against key pro-inflammatory cytokines using cell viability assay, TUNEL and flow cytometry. Further, naïve primary astrocytes were treated with UV-inactivated supernatant from mock- and WNV-infected SK-N-SH cell line and the activation of astrocytes was measured using flow cytometry and ELISA. Results WNV-infected SK-N-SH cells induced the expression of IL-1β, -6, -8, and TNF-α in a dose- and time-dependent manner, which coincided with increase in virus-induced cell death. Treatment of cells with anti-IL-1β or -TNF-α resulted in significant reduction of the neurotoxic effects of WNV. Furthermore treatment of naïve astrocytes with UV-inactivated supernatant from WNV-infected SK-N-SH cell line increased expression of glial fibrillary acidic protein and key inflammatory cytokines. Conclusion Our results for the first time suggest that neurons are one of the potential sources of pro-inflammatory cytokines in WNV-infected brain and these neuron-derived cytokines contribute to WNV

  8. Strengthening air traffic safety management by moving from outcome-based towards risk-based evaluation of runway incursions

    International Nuclear Information System (INIS)

    Stroeve, Sybert H.; Som, Pradip; Doorn, Bas A. van; Bakker, G.J.

    2016-01-01

    Current safety management of aerodrome operations uses judgements of severity categories to evaluate runway incursions. Incident data show a small minority of severe incursions and a large majority of less severe incursions. We show that these severity judgements are mainly based upon the outcomes of runway incursions, in particular on the closest distances attained. As such, the severity-based evaluation leads to coincidental safety management feedback, wherein causes and risk implications of runway incursions are not well considered. In this paper we present a new framework for the evaluation of runway incursions, which effectively uses all runway incursions, which judges same types of causes similarly, and which structures causes and risk implications. The framework is based on risks of scenarios associated with the initiation of runway incursions. As a basis an inventory of scenarios is provided, which can represent almost all runway incursions involving a conflict with an aircraft. A main step in the framework is the assessment of the conditional probability of a collision given a runway incursion scenario. This can be effectively achieved for large sets of scenarios by agent-based dynamic risk modelling. The results provide detailed feedback on risks of runway incursion scenarios, thus enabling effective safety management. - Highlights: • Current evaluation of runway incursions is primarily based on their outcomes. • A new framework assesses collision risk given initiation of runway incursions. • Agent-based dynamic risk modelling can evaluate the risks of many scenarios. • A developed scenario inventory can represent almost all runway incursions. • The framework provides detailed feedback to safety management.

  9. A recombinant novirhabdovirus presenting at the surface the E Glycoprotein from West Nile Virus (WNV is immunogenic and provides partial protection against lethal WNV challenge in BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Angella Nzonza

    Full Text Available West Nile Virus (WNV is a zoonotic mosquito-transmitted flavivirus that can infect and cause disease in mammals including humans. Our study aimed at developing a WNV vectored vaccine based on a fish Novirhabdovirus, the Viral Hemorrhagic Septicemia virus (VHSV. VHSV replicates at temperatures lower than 20°C and is naturally inactivated at higher temperatures. A reverse genetics system has recently been developed in our laboratory for VHSV allowing the addition of genes in the viral genome and the recovery of the respective recombinant viruses (rVHSV. In this study, we have generated rVHSV vectors bearing the complete WNV envelope gene (EWNV (rVHSV-EWNV or fragments encoding E subdomains (either domain III alone or domain III fused to domain II (rVHSV-DIIIWNV and rVHSV-DII-DIIIWNV, respectively in the VHSV genome between the N and P cistrons. With the objective to enhance the targeting of the EWNV protein or EWNV-derived domains to the surface of VHSV virions, Novirhadovirus G-derived signal peptide and transmembrane domain (SPG and TMG were fused to EWNV at its amino and carboxy termini, respectively. By Western-blot analysis, electron microscopy observations or inoculation experiments in mice, we demonstrated that both the EWNV and the DIIIWNV could be expressed at the viral surface of rVHSV upon addition of SPG. Every constructs expressing EWNV fused to SPG protected 40 to 50% of BALB/cJ mice against WNV lethal challenge and specifically rVHSV-SPGEWNV induced a neutralizing antibody response that correlated with protection. Surprisingly, rVHSV expressing EWNV-derived domain III or II and III were unable to protect mice against WNV challenge, although these domains were highly incorporated in the virion and expressed at the viral surface. In this study we demonstrated that a heterologous glycoprotein and non membrane-anchored protein, can be efficiently expressed at the surface of rVHSV making this approach attractive to develop new vaccines

  10. Effect of serum heat-inactivation and dilution on detection of anti-WNV antibodies in mice by West Nile virus E-protein microsphere immunoassay.

    Directory of Open Access Journals (Sweden)

    Madhuri Namekar

    Full Text Available Immunopathogenesis studies employing West Nile virus (WNV mice model are important for the development of antivirals and vaccines against WNV. Since antibodies produced in mice early during WNV infection are essential for clearing virus from the periphery, it is important to detect early and persistent anti-WNV antibodies. ELISA and plaque reduction neutralization tests are traditionally used for detection of anti-WNV antibodies and WNV-neutralizing antibodies, respectively. Although these assays are sensitive and specific, they are expensive and time consuming. Microsphere immunoassays (MIA are sensitive, specific, allow for high throughput, are cost effective, require less time to perform than other methods, and require low serum volumes. Several assay parameters such as serum heat-inactivation (HI and dilution can alter WNV MIA sensitivity. We examined the effect of these parameters on WNV E-protein MIA (WNV E-MIA for the enhanced detection of anti-WNV IgM and IgG antibodies. WNV E-MIA was conducted using serial dilutions of HI and non-HI (NHI serum collected at various time points from mice inoculated with WNV. HI significantly enhanced detection of IgM and IgG antibodies as compared to NHI serum. WNV IgM and IgG antibodies in HI sera were detected earlier at day 3 and IgM antibodies persisted up to day 24 after infection. HI serum at 1∶20 dilution was found to be optimal for detection of both IgM and IgG antibodies as compared to higher-serum dilutions. Further, addition of exogenous complement to the HI serum decreased the WNV E-MIA sensitivity. These results suggest that serum-HI and optimal dilution enhance WNV E-MIA sensitivity by eliminating the complement interference, thereby detecting low-titer anti-WNV antibodies during early and late phases of infection. This improved MIA can also be readily employed for detection of low-titer antibodies for detection of other infectious agents and host proteins.

  11. An assessment of predominant causal factors of pilot deviations that contribute to runway incursions

    Science.gov (United States)

    Campbell, Denado M.

    The aim of this study was to identify predominant causal factors of pilot deviations in runway incursions over a two-year period. Runway incursion reports were obtained from NASA's Aviation Safety Reporting System (ASRS), and a qualitative method was used by classifying and coding each report to a specific causal factor(s). The causal factors that were used were substantiated by research from the Aircraft Owner's and Pilot's Association that found that these causal factors were the most common in runway incursion incidents and accidents. An additional causal factor was also utilized to determine the significance of pilot training in relation to runway incursions. From the reports examined, it was found that miscommunication and situational awareness have the greatest impact on pilots and are most often the major causes of runway incursions. This data can be used to assist airports, airlines, and the FAA to understand trends in pilot deviations, and to find solutions for specific problem areas in runway incursion incidents.

  12. Assessing the impact of climate change on vector-borne viruses in the EU through the elicitation of expert opinion.

    Science.gov (United States)

    Gale, P; Brouwer, A; Ramnial, V; Kelly, L; Kosmider, R; Fooks, A R; Snary, E L

    2010-02-01

    Expert opinion was elicited to undertake a qualitative risk assessment to estimate the current and future risks to the European Union (EU) from five vector-borne viruses listed by the World Organization for Animal Health. It was predicted that climate change will increase the risk of incursions of African horse sickness virus (AHSV), Crimean-Congo haemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV) into the EU from other parts of the world, with African swine fever virus (ASFV) and West Nile virus (WNV) being less affected. Currently the predicted risks of incursion were lowest for RVFV and highest for ASFV. Risks of incursion were considered for six routes of entry (namely vectors, livestock, meat products, wildlife, pets and people). Climate change was predicted to increase the risk of incursion from entry of vectors for all five viruses to some degree, the strongest effects being predicted for AHSV, CCHFV and WNV. This work will facilitate identification of appropriate risk management options in relation to adaptations to climate change.

  13. Protection of horses from West Nile virus Lineage 2 challenge following immunization with a whole, inactivated WNV lineage 1 vaccine.

    Science.gov (United States)

    Bowen, Richard A; Bosco-Lauth, Angela; Syvrud, Kevin; Thomas, Anne; Meinert, Todd R; Ludlow, Deborah R; Cook, Corey; Salt, Jeremy; Ons, Ellen

    2014-09-22

    Over the last years West Nile virus (WNV) lineage 2 has spread from the African to the European continent. This study was conducted to demonstrate efficacy of an inactivated, lineage 1-based, WNV vaccine (Equip WNV) against intrathecal challenge of horses with a recent isolate of lineage 2 WNV. Twenty horses, sero-negative for WNV, were enrolled and were randomly allocated to one of two treatment groups: an unvaccinated control group (T01, n=10) and a group administered with Equip WNV (T02, n=10). Horses were vaccinated at Day 0 and 21 and were challenged at day 42 with WNV lineage 2, Nea Santa/Greece/2010. Personnel performing clinical observations were blinded to treatment allocation. Sixty percent of the controls had to be euthanized after challenge compared to none of the vaccinates. A significantly lower percentage of the vaccinated animals showed clinical disease (two different clinical observations present on the same day) on six different days of study and the percentage of days with clinical disease was significantly lower in the vaccinated group. A total of 80% of the non-vaccinated horses showed viremia while only one vaccinated animal was positive by virus isolation on a single occasion. Vaccinated animals started to develop antibodies against WNV lineage 2 from day 14 (2 weeks after the first vaccination) and at day 42 (the time of onset of immunity) they had all developed a strong antibody response. Histopathology scores for all unvaccinated animals ranged from mild to very severe in each of the tissues examined (cervical spinal cord, medulla and pons), whereas in vaccinated horses 8 of 10 animals had no lesions and 2 had minimal lesions in one tissue. In conclusion, Equip WNV significantly reduced the number of viremic horses, the duration and severity of clinical signs of disease and mortality following challenge with lineage 2 WNV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. [The Impact of Visual Perceptual Abilities on the Performance on the Wechsler Nonverbal Scale of Ability (WNV)].

    Science.gov (United States)

    Werpup-Stüwe, L; Petermann, F; Daseking, M

    2015-10-01

    The use of psychometric tests in with children and adolescents is especially important in psychological diagnostics. Nonverbal intelligence tests are very often used to diagnose psychological abnormalities and generate developmental prognosis independent of the child´s verbal abilities. The correlation of the German version of the Developmental Test of Visual Perception - Adolescents and Adults (DTVP-A) with the Wechsler Nonverbal Scala of Abilities (WNV) was calculated based on the results of 172 children, adolescents and young adults aged 9-21 years. Furthermore, it was examined if individuals with poor visual perceptual abilities scored lower on the WNV than healthy subjects. The correlations of the results scored on DTVP-A and WNV ranged from moderate to strong. The group with poor visual perceptual abilities scored significantly lower on the WNV than the control group. Nonverbal intelligence tests like the WNV are not reliable for estimating the intelligence of individuals with low visual perceptual abilities. Therefore, the intelligence of these subjects should be tested with a test that also contains verbal subtests. If poor visual perceptual abilities are suspected, then they should be tested. The DTVP-A seems to be the right instrument for achieving this goal. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Late Neogene marine incursions and the ancestral Gulf of California

    Science.gov (United States)

    McDougall, K.

    2008-01-01

    The late Neogene section in the Salton Trough, California, and along the lower Colorado River in Arizona is composed of marine units bracketed by nonmarine units. Microfossils from the marine deposits indicate that a marine incursion inundated the Salton Trough during the late Miocene. Water depths increased rapidly in the Miocene and eventually flooded the region now occupied by the Colorado River as far north as Parker, Arizona. Marine conditions were restricted in the Pliocene as the Colorado River filled the Salton Trough with sediments and the Gulf of California assumed its present configuration. Microfossils from the early part of this incursion include a diverse assemblage of benthic foraminifers (Amphistegina gibbosa, Uvigerina peregrina, Cassidulina delicata, and Bolivina interjuncta), planktic foraminifers (Globigerinoides obliquus, G. extremus, and Globigerina nepenthes), and calcareous nannoplankton (Discoaster brouweri, Discoaster aff. Discoaster surculus, Sphenolithus abies, and S. neoabies), whereas microfossils in the final phase contain a less diverse assemblage of benthic foraminifers that are diagnostic of marginal shallow-marine conditions (Ammonia, Elphidium, Bolivina, Cibicides, and Quinqueloculina). Evidence of an earlier middle Miocene marine incursion comes from reworked microfossils found near Split Mountain Gorge in the Fish Creek Gypsum (Sphenolithus moriformis) and near San Gorgonio Pass (Cyclicargolithus floridanus and Sphenolithus heteromorphus and planktic foraminifers). The middle Miocene incursion may also be represented by the older marine sedimentary rocks encountered in the subsurface near Yuma, Arizona, where rare middle Miocene planktic foraminifers are found. ?? 2008 The Geological Society of America.

  16. Syndromic surveillance for West Nile virus using raptors in rehabilitation.

    Science.gov (United States)

    Ana, Alba; Perez Andrés, M; Julia, Ponder; Pedro, Puig; Arno, Wünschmann; Kimberly, Vander Waal; Julio, Alvarez; Michelle, Willette

    2017-11-29

    Wildlife rehabilitation centers routinely gather health-related data from diverse species. Their capability to signal the occurrence of emerging pathogens and improve traditional surveillance remains largely unexplored. This paper assessed the utility for syndromic surveillance of raptors admitted to The Raptor Center (TRC) to signal circulation of West Nile Virus (WNV) in Minnesota between 1990 and 2014. An exhaustive descriptive analysis using grouping time series structures and models of interrupted times series was conducted for indicator subsets. A total of 13,080 raptors were monitored. The most representative species were red-tailed hawks, great horned owls, Cooper's hawks, American kestrels and bald eagles. Results indicated that temporal patterns of accessions at the TRC changed distinctively after the incursion of WNV in 2002. The frequency of hawks showing WNV-like signs increased almost 3 times during July and August, suggesting that monitoring of hawks admitted to TRC with WNV-like signs could serve as an indicator of WNV circulation. These findings were also supported by the results of laboratory diagnosis. This study demonstrates that monitoring of data routinely collected by wildlife rehabilitation centers has the potential to signal the spread of pathogens that may affect wild, domestic animals and humans, thus supporting the early detection of disease incursions in a region and monitoring of disease trends. Ultimately, data collected in rehabilitation centers may provide insights to efficiently allocate financial and human resources on disease prevention and surveillance.

  17. Using avian surveillance in Ecuador to assess the imminence of West Nile virus incursion to Galápagos.

    Science.gov (United States)

    Eastwood, Gillian; Goodman, Simon J; Hilgert, Nancy; Cruz, Marilyn; Kramer, Laura D; Cunningham, Andrew A

    2014-01-01

    Infectious disease emergence represents a global threat to human, agricultural animal and wildlife health. West Nile virus (WNV) first emerged in the Americas in 1999 following its introduction to New York from the Old World. This flavivirus rapidly spread across much of North America, causing human, equine and avian mortalities and population declines of multiple wild bird species. It has now spread to Central and South America, and there is concern that the virus will reach the Galápagos Islands, a UNESCO World Heritage Site famous for its unique biodiversity, with potentially catastrophic results. Here, we use wild bird surveillance to examine the current WNV status in the Galapagos Islands and around the Ecuadorian city of Guayaquil (the main air and sea port serving Galápagos). We conducted serosurveys of wild birds on three Galápagos Islands (Baltra, San Cristobal and Santa Cruz) with direct transport links to the South American continent. In addition, dead birds killed by car collisions on Santa Cruz were tested for WNV infection. On mainland Ecuador, serosurveys of wild birds were conducted at three sites around Guayaquil. No evidence of WNV seropositivity or infection was detected. Although wider testing is recommended on the mainland, the study highlights a limit of WNV spread within South America. Our results indicate the continued absence of WNV on Galápagos and suggest the current likelihood of human-mediated transport of WNV to Galápagos to be low. The risk of emergence will almost certainly increase over time, however, and stringent biosecurity and surveillance measures should be put in place to minimise the risk of the introduction of WNV (and other alien pathogens) to Galápagos.

  18. Internally deleted WNV genomes isolated from exotic birds in New Mexico: function in cells, mosquitoes, and mice.

    Science.gov (United States)

    Pesko, Kendra N; Fitzpatrick, Kelly A; Ryan, Elizabeth M; Shi, Pei-Yong; Zhang, Bo; Lennon, Niall J; Newman, Ruchi M; Henn, Matthew R; Ebel, Gregory D

    2012-05-25

    Most RNA viruses exist in their hosts as a heterogeneous population of related variants. Due to error prone replication, mutants are constantly generated which may differ in individual fitness from the population as a whole. Here we characterize three WNV isolates that contain, along with full-length genomes, mutants with large internal deletions to structural and nonstructural protein-coding regions. The isolates were all obtained from lorikeets that died from WNV at the Rio Grande Zoo in Albuquerque, NM between 2005 and 2007. The deletions are approximately 2kb, in frame, and result in the elimination of the complete envelope, and portions of the prM and NS-1 proteins. In Vero cell culture, these internally deleted WNV genomes function as defective interfering particles, reducing the production of full-length virus when introduced at high multiplicities of infection. In mosquitoes, the shortened WNV genomes reduced infection and dissemination rates, and virus titers overall, and were not detected in legs or salivary secretions at 14 or 21 days post-infection. In mice, inoculation with internally deleted genomes did not attenuate pathogenesis relative to full-length or infectious clone derived virus, and shortened genomes were not detected in mice at the time of death. These observations provide evidence that large deletions may occur within flavivirus populations more frequently than has generally been appreciated and suggest that they impact population phenotype minimally. Additionally, our findings suggest that highly similar mutants may frequently occur in particular vertebrate hosts. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Analysis of Runway Incursion Data

    Science.gov (United States)

    Green, Lawrence L.

    2013-01-01

    A statistical analysis of runway incursion (RI) events was conducted to ascertain relevance to the top ten challenges of the National Aeronautics and Space Administration Aviation Safety Program (AvSP). The information contained in the RI database was found to contain data that may be relevant to several of the AvSP top ten challenges. When combined with other data from the FAA documenting air traffic volume from calendar year 2000 through 2011, the structure of a predictive model emerges that can be used to forecast the frequency of RI events at various airports for various classes of aircraft and under various environmental conditions.

  20. Second International Diagnostic Accuracy Study for the Serological Detection of West Nile Virus Infection

    OpenAIRE

    Sanchini, Andrea; Donoso-Mantke, Oliver; Papa, Anna; Sambri, Vittorio; Teichmann, Anette; Niedrig, Matthias

    2013-01-01

    Background: In recent decades, sporadic cases and outbreaks in humans of West Nile virus (WNV) infection have increased. Serological diagnosis of WNV infection can be performed by enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA) neutralization test (NT) and by hemagglutination-inhibition assay. The aim of this study is to collect updated information regarding the performance accuracy of WNV serological diagnostics. Methodology/Principal findings: In 2011, the E...

  1. Smoke incursions into urban areas: simulation of a Georgia prescribed burn

    Science.gov (United States)

    Y. Liu; S. Goodrick; G. Achtemeier

    2009-01-01

    This study investigates smoke incursion into urban areas by examining a prescribed burn in central Georgia,USA, on 28 February 2007. Simulations were conducted with a regional modeling framework to understand transport, dispersion,and structure of smoke plumes, the air quality effects, sensitivity to emissions,...

  2. Pandemic influenza A/H1N1 virus incursion into Africa: countries ...

    African Journals Online (AJOL)

    Pandemic influenza A/H1N1 virus incursion into Africa: countries, hosts and ... features are important for planning control measures between countries and to ... in humans, infections in pigs earlier reported in America, Europe and Asia were ...

  3. Runway Incursion Prevention System: Demonstration and Testing at the Dallas/Fort Worth International Airport

    Science.gov (United States)

    Jones, Denise R.; Quach, Cuong C.; Young, Steven D.

    2007-01-01

    A Runway Incursion Prevention System (RIPS) was tested at the Dallas-Ft. Worth International Airport (DFW) in October 2000. The system integrated airborne and ground components to provide both pilots and controllers with enhanced situational awareness, supplemental guidance cues, a real-time display of traffic information, and warning of runway incursions in order to prevent runway incidents while also improving operational capability. A series of test runs was conducted using NASA s Boeing 757 research aircraft and a test van equipped to emulate an incurring aircraft. The system was also demonstrated to over 100 visitors from the aviation community. This paper gives an overview of the RIPS, DFW flight test activities, and quantitative and qualitative results of the testing.

  4. West Nile Virus and Usutu Virus Monitoring of Wild Birds in Germany

    Science.gov (United States)

    Michel, Friederike; Fast, Christine; Reuschel, Maximilian; Müller, Kerstin; Urbaniak, Sylvia; Brandes, Florian; Schwehn, Rebekka; Groschup, Martin H.; Ziegler, Ute

    2018-01-01

    By systematically setting up a unique nation-wide wild bird surveillance network, we monitored migratory and resident birds for zoonotic arthropod-borne virus infections, such as the flaviviruses West Nile virus (WNV) and Usutu virus (USUV). More than 1900 wild bird blood samples, from 20 orders and 136 different bird species, were collected between 2014 and 2016. Samples were investigated by WNV and USUV-specific real-time polymerase chain reactions as well as by differentiating virus neutralization tests. Dead bird surveillance data, obtained from organ investigations in 2016, were also included. WNV-specific RNA was not detected, whereas four wild bird blood samples tested positive for USUV-specific RNA. Additionally, 73 USUV-positive birds were detected in the 2016 dead bird surveillance. WNV neutralizing antibodies were predominantly found in long-distance, partial and short-distance migrants, while USUV neutralizing antibodies were mainly detected in resident wild bird species, preferentially with low seroprevalences. To date, WNV-specific RNA has neither been detected in wild birds, nor in mosquitoes, thus, we conclude that WNV is not yet present in Germany. Continued wild bird and mosquito monitoring studies are essential to detect the incursion of zoonotic viruses and to allow risk assessments for zoonotic pathogens. PMID:29361762

  5. An early warning system for incursions of Bluetongue disease to the UK

    Science.gov (United States)

    Burgin, Laura; Sanders, Christopher; Carpenter, Simon; Mellor, Philip; Gloster, John

    2010-05-01

    Since 2006 northern Europe has been in the midst of an extensive epidemic of the animal disease, Bluetongue, which has cost the European economy hundreds of millions of euros due to death, sickness and movement restrictions of livestock. Bluetongue is spread by biting midges which can be carried for hundreds of kilometers on the wind. A scheme within the UK Met Office's dispersion model, the Numerical Atmospheric-dispersion Modelling Environment (NAME), has been developed to reflect the effects of meteorology on the long-distance transport of these midge vectors. The scheme is based on data from field and laboratory experiments carried out at the Institute for Animal Health, Pirbright. From these experiments, certain threshold values which define when midges do not become airborne have been obtained for several meteorological variables. Within NAME, particles representing midges are removed from the model atmosphere if these thresholds are exceeded. Following outbreaks of the disease in Belgium and the Netherlands in 2006, an early-warning website was developed based on the model, to provide the UK Department for Environment, Food and Rural Affairs (Defra) advance knowledge of potential disease incursions by infected midges carried on the wind across the English Channel. The service has been in daily operation since April 2007 and correctly warned of the high risk of an incursion of infected midges causing the first UK outbreak in Suffolk on 4 August 2007. The website has since been expanded to predict potential incursions of disease into the Channel Islands and Northern Ireland and was used to inform on vaccination policy decisions by Defra and the Scottish government.

  6. Assessing the consequences of an incursion of a vector-borne disease. II. Spread of bluetongue in Scotland and impact of vaccination

    Directory of Open Access Journals (Sweden)

    Camille Szmaragd

    2010-09-01

    Full Text Available Bluetongue is a viral disease of ruminants transmitted by Culicoides biting midges, which has spread across Europe over the past decade. The disease arrived in south-east England in 2007, raising the possibility that it could pose a risk to the valuable Scottish livestock industry. As part of an assessment of the economic consequences of a bluetongue virus incursion into Scotland commissioned by Scottish Government, we investigated a defined set of feasible incursion scenarios under different vaccination strategies. Our epidemiological simulations, based on expert knowledge, highlighted that infection will rarely spread in Scotland after the initial incursion and will be efficiently controlled by vaccination. Keywords: Epidemiology, modelling, disease control

  7. KENYA’S PRE - EMPTIVE AND PREVENTIVE INCURSION AGAINST AL - SHABAAB IN THE LIGHT OF INTERNATIONAL LAW

    Directory of Open Access Journals (Sweden)

    E.O.S. ODHIAMBO

    2012-01-01

    Full Text Available Al-Shabaab terrorist group’s series of kidnappings and cross-border incursions into Kenya threatened security and the lucrative tourism industry in East Africa's largest economy. Towards the end of 2011 events like the kidnapping of two foreigners and the killing of another in the Kenyan resorts on the east coast, the abduction of two aid workers from the Dadaab refugee camp, and the attack against Kenyan soldiers in cross-border raids raised a lot of concern for the Kenyan government. Consequently, the latter decided that the national security interest of Kenya had to be protected. As a result, the decision of the government was to go to war against Al- Shabaab. This prompted the Kenya Defence Forces’ (KDF incursion to Somalia in a pre-emptive and preventive campaign aimed at fl ushing out Al-Shabaab from this country. The campaign took off in mid-October 2011 and it was dubbed “Operation Linda Nchi”, Swahili for “Protect the country’. In this article we look at the implication of Kenya’s pre-emptive and preventive incursion against Al- Shabaab from the perspective of international law.

  8. Genetics Home Reference: sporadic hemiplegic migraine

    Science.gov (United States)

    ... Home Health Conditions Sporadic hemiplegic migraine Sporadic hemiplegic migraine Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Sporadic hemiplegic migraine is a rare form of migraine headache. Migraines ...

  9. A Sensor-based System for Monitoring Hard-shoulder Incursions: Review of Technologies and Selection Criteria

    Directory of Open Access Journals (Sweden)

    Michalaki Paraskevi

    2016-01-01

    Full Text Available According to safety observations from motorway operators in the United Kingdom, the hard-shoulder is occasionally violated by road users travelling in the nearside lane. These unintentional movements (hard-shoulder incursions can impose risk to operatives performing activities on the network. To further investigate these events, a sensor-based system can be used for monitoring them and collecting related data such as severity of incursion and vehicle classification. A review of vehicle detection technologies that could be applied for this purpose is presented, along with the criteria for selection of the most suitable technology and implementation sites. Two potential non-intrusive systems are also described, a laser- and a radar-based systems, which provide different levels of flexibility and data.

  10. Comparison Between Sporadic and Misdiagnosed Sporadic Creutzfeldt-Jakob Disease: A Report of Two Cases.

    Science.gov (United States)

    Zhao, Xiongfei; Yu, Yingxin; Zhao, Zhiru; Xu, Jiaping

    2015-06-01

    Definite accurate diagnosis for Creutzfeldt-Jakob disease (CJD) depends on neuropathologic examination of brain biopsy or autopsy. However, transmissible nature makes the invasive examination dangerous. This study was set to determine that the clinical features are for the diagnosis of CJD through a comparison study. We compared clinical features of two cases with initial diagnosis of sporadic CJD. One case was finally diagnosed as definite sporadic CJD. According to World Health Organization diagnosis criteria, the other one, which had been diagnosed as probable sporadic CJD, was confirmed as limbic encephalitis after long-term follow-up. Compared with the case of definite sporadic CJD, the misdiagnosed case did not present typical electroencephalogram (EEG) and diffusion-weighted in magnetic resonance images (DWI) of CJD. However, cerebrospinal fluid in the misdiagnosed patient showed 14-3-3 protein positivity. The patient conditions improved after treatment. Through this case comparison, we conclude that EEG and DWI are necessary for accurate diagnosis of sporadic CJD. Further, long-term follow-up is crucial to diagnosis and treatment of CJD.

  11. Introduction to Sporadic Groups

    Directory of Open Access Journals (Sweden)

    Luis J. Boya

    2011-01-01

    Full Text Available This is an introduction to finite simple groups, in particular sporadic groups, intended for physicists. After a short review of group theory, we enumerate the 1+1+16=18 families of finite simple groups, as an introduction to the sporadic groups. These are described next, in three levels of increasing complexity, plus the six isolated ''pariah'' groups. The (old five Mathieu groups make up the first, smallest order level. The seven groups related to the Leech lattice, including the three Conway groups, constitute the second level. The third and highest level contains the Monster group M, plus seven other related groups. Next a brief mention is made of the remaining six pariah groups, thus completing the 5+7+8+6=26 sporadic groups. The review ends up with a brief discussion of a few of physical applications of finite groups in physics, including a couple of recent examples which use sporadic groups.

  12. Runway Safety: It's Everybody's Business. We Want You to Put the Brakes on Runway Incursions

    National Research Council Canada - National Science Library

    Cardosi, Kim

    2001-01-01

    This booklet tell pilots and controllers what they can do to help prevent runway incursions by helping them to avoid situations that induce errors and alerting them to them to situations as extra vigilance is required...

  13. The Integrated System for Public Health Monitoring of West Nile Virus (ISPHM-WNV: a real-time GIS for surveillance and decision-making

    Directory of Open Access Journals (Sweden)

    Lebel Germain

    2005-09-01

    Full Text Available Abstract Background After its first detection in North America in New York in 1999, West Nile virus was detected for the first time in 2002 in the province of Quebec, Canada. This situation forced the Government of Quebec to adopt a public health protection plan against the virus. The plan comprises several fields of intervention including the monitoring of human cases, Corvidae and mosquitoes in order to ensure the early detection of the presence of the virus in a particular area. To help support the monitoring activities, the Integrated System for Public Health Monitoring of West Nile Virus (ISPHM-WNV has been developed. Results The ISPHM-WNV is a real-time geographic information system for public health surveillance of West Nile virus and includes information on Corvidae, mosquitoes, humans, horses, climate, and preventive larvicide interventions. It has been in operation in the province of Quebec, Canada, since May 2003. The ISPHM-WNV facilitates the collection, localization, management and analysis of monitoring data; it also allows for the display of the results of analyses on maps, tables and statistical diagrams. Conclusion The system is very helpful for field workers in all regions of the province, as well as for central authorities. It represents the common authoritative source of data for analysis, exchange and decision-making.

  14. Sporadic Fatal Insomnia in an Adolescent

    Science.gov (United States)

    Blase, Jennifer L.; Cracco, Laura; Schonberger, Lawrence B.; Maddox, Ryan A.; Cohen, Yvonne; Cali, Ignazio

    2014-01-01

    The occurrence of sporadic prion disease among adolescents is extremely rare. A prion disease was confirmed in an adolescent with disease onset at 13 years of age. Genetic, neuropathologic, and biochemical analyses of the patient’s autopsy brain tissue were consistent with sporadic fatal insomnia, a type of sporadic prion disease. There was no evidence of an environmental source of infection, and this patient represents the youngest documented case of sporadic prion disease. Although rare, a prion disease diagnosis should not be discounted in adolescents exhibiting neurologic signs. Brain tissue testing is necessary for disease confirmation and is particularly beneficial in cases with an unusual clinical presentation. PMID:24488737

  15. Factors associated with secondhand smoke incursion into the homes of non-smoking residents in a multi-unit housing complex: a cross-sectional study in Seoul, Korea

    Directory of Open Access Journals (Sweden)

    Jeonghoon Kim

    2017-09-01

    Full Text Available Abstract Background In a multi-unit housing (MUH complex, secondhand smoke (SHS can pass from one living space to another. The aim of this study was to determine the prevalence of SHS incursion, and to establish the relationship between SHS incursion and socio-demographic and built environmental factors in MUH in Korea. Methods A population-based sample of 2600 residents (aged ≥19 years living in MUH from across the city of Seoul, Korea, was obtained through a web-based selection panel. The residents completed a questionnaire detailing socio-demographic factors, smoking status, frequency of SHS incursion, and built environmental factors. The presence of a personal smoke-free home rule was determined by residents declaring that no one smoked inside the home. Results Of the 2600 participants, non-smoking residents who lived in homes with a personal smoke-free rule were selected for further analysis (n = 1784. In the previous 12 months, 74.7% of residents had experienced SHS incursion ≥1 times. A multivariate ordinal logistic regression analysis indicated that residents who spent more time at home, lived with children, supported the implementation of smoke-free regulations in MUH, lived in small homes, lived in homes with natural ventilation provided by opening a front door or the windows and front door, and lived in homes with more frequent natural ventilation were more likely to report SHS incursion into their homes. Conclusions The majority of the non-smoking residents experienced SHS incursion, even with a personal smoke-free rule in their homes. A smoke-free policy in MUH is needed to protect residents from SHS exposure when they are at home.

  16. Adult onset sporadic ataxias: a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Orlando Graziani Povoas Barsottini

    2014-03-01

    Full Text Available Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic conditions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

  17. Investigation on the relationship among sporadic Na, sporadic E, Field aligned irregularities and neutral winds

    Science.gov (United States)

    Sundararajan, Sridharan; Patra, Amit Kumar; Pant, Tarun; Gurubaran, Subramanian; Raghunath, Karnam

    In the Mesosphere and Lower Thermosphere region (80-100 km), metallic atoms, namely, sodium, potassium, lithium, Iron etc are formed due to ablation of meteors. The lidars based on resonance fluorescence principle has been used to study the vertical distribution of sodium atoms, because of their large abundance than other metals. The profiles of sodium density sometimes show enhancement by a factor of 2 than the normal layer in a narrow altitude region of 2 km and on these occasions, they are called sporadic sodium layer, or briefly Ns. On the other hand, there are observations on sporadic E and radar observations of Field Aligned Irregularities (FAI) associated with these sporadic E. Some investigations have been made to understand the relationship between sporadic E and FAI. Considering that sporadic E is composed of metallic ions and the time of metallic ions are larger compared to other ions, the sodium observations in the same height region would be of significant importance to understand the process involved. Despite a few past observations, no clear picture has emerged due to lack of simultaneous measurements of these parameters. The simultaneous observations of FAI echoes by the Indian MST radar and sodium concentration by the sodium lidar at Gadanki (13.5o N, 79.2o E) are being used to investigate the above mentioned relationship. The Sporadic E and neutral wind information are obtained from the ionosonde, meteor/MF radar observations from Trivandrum (8.5o N, 77E) and Tirunelveli (8.7o N, 77.8o E). The results obtained will be presented during the meeting.

  18. Association of radiowave absorption with E(sporadic)-activity

    International Nuclear Information System (INIS)

    Ganguly, S.

    1975-01-01

    Noontime radiowave absorption data for frequencies which are reflected below the height of sporadic-E layers show a strong positive correlation with the sporadic-E layer activity. The possibilities of atmospheric waves affecting both the sporadic-E activity as well as mesospheric ionization are suggested to explain this association

  19. Predicting incursion of plant invaders into Kruger National Park, South Africa: the interplay of general drivers and species-specific factors.

    Directory of Open Access Journals (Sweden)

    Vojtěch Jarošík

    Full Text Available BACKGROUND: Overcoming boundaries is crucial for incursion of alien plant species and their successful naturalization and invasion within protected areas. Previous work showed that in Kruger National Park, South Africa, this process can be quantified and that factors determining the incursion of invasive species can be identified and predicted confidently. Here we explore the similarity between determinants of incursions identified by the general model based on a multispecies assemblage, and those identified by species-specific models. We analyzed the presence and absence of six invasive plant species in 1.0×1.5 km segments along the border of the park as a function of environmental characteristics from outside and inside the KNP boundary, using two data-mining techniques: classification trees and random forests. PRINCIPAL FINDINGS: The occurrence of Ageratum houstonianum, Chromolaena odorata, Xanthium strumarium, Argemone ochroleuca, Opuntia stricta and Lantana camara can be reliably predicted based on landscape characteristics identified by the general multispecies model, namely water runoff from surrounding watersheds and road density in a 10 km radius. The presence of main rivers and species-specific combinations of vegetation types are reliable predictors from inside the park. CONCLUSIONS: The predictors from the outside and inside of the park are complementary, and are approximately equally reliable for explaining the presence/absence of current invaders; those from the inside are, however, more reliable for predicting future invasions. Landscape characteristics determined as crucial predictors from outside the KNP serve as guidelines for management to enact proactive interventions to manipulate landscape features near the KNP to prevent further incursions. Predictors from the inside the KNP can be used reliably to identify high-risk areas to improve the cost-effectiveness of management, to locate invasive plants and target them for

  20. Predicting Incursion of Plant Invaders into Kruger National Park, South Africa: The Interplay of General Drivers and Species-Specific Factors

    Science.gov (United States)

    Jarošík, Vojtěch; Pyšek, Petr; Foxcroft, Llewellyn C.; Richardson, David M.; Rouget, Mathieu; MacFadyen, Sandra

    2011-01-01

    Background Overcoming boundaries is crucial for incursion of alien plant species and their successful naturalization and invasion within protected areas. Previous work showed that in Kruger National Park, South Africa, this process can be quantified and that factors determining the incursion of invasive species can be identified and predicted confidently. Here we explore the similarity between determinants of incursions identified by the general model based on a multispecies assemblage, and those identified by species-specific models. We analyzed the presence and absence of six invasive plant species in 1.0×1.5 km segments along the border of the park as a function of environmental characteristics from outside and inside the KNP boundary, using two data-mining techniques: classification trees and random forests. Principal Findings The occurrence of Ageratum houstonianum, Chromolaena odorata, Xanthium strumarium, Argemone ochroleuca, Opuntia stricta and Lantana camara can be reliably predicted based on landscape characteristics identified by the general multispecies model, namely water runoff from surrounding watersheds and road density in a 10 km radius. The presence of main rivers and species-specific combinations of vegetation types are reliable predictors from inside the park. Conclusions The predictors from the outside and inside of the park are complementary, and are approximately equally reliable for explaining the presence/absence of current invaders; those from the inside are, however, more reliable for predicting future invasions. Landscape characteristics determined as crucial predictors from outside the KNP serve as guidelines for management to enact proactive interventions to manipulate landscape features near the KNP to prevent further incursions. Predictors from the inside the KNP can be used reliably to identify high-risk areas to improve the cost-effectiveness of management, to locate invasive plants and target them for eradication. PMID:22194893

  1. A Survey of Dog Owners in Remote Northern Australian Indigenous Communities to Inform Rabies Incursion Planning.

    Directory of Open Access Journals (Sweden)

    Emily G Hudson

    2016-04-01

    Full Text Available Australia is underprepared for a rabies incursion due to a lack of information about how a rabies outbreak would spread within the susceptible canine populations and which control strategies would be best to control it. The aim of this study was to collect information to parameterize a recently developed dog rabies spread model as well as use this information to gauge how the community would accept potential control strategies. Such information-together with model outputs-would be used to inform decision makers on the best control strategies and improve Australia's preparedness against a canine rabies incursion. The parameters this study focussed on were detection time, vaccination rates and dog-culling and dog movement restriction compliance. A cross-sectional survey of 31 dog-owners, using a questionnaire, was undertaken in the five communities of the Northern Peninsular Area (NPA in northern Australia regarding community dog movements, veterinary visits, reporting systems, perceptions of sick dogs and potential human behaviours during hypothetical rabies outbreaks. It highlighted the significant shortfalls in veterinary care that would need to be vastly improved during an outbreak, who educational programs should be targeted towards and which dog movements should be restricted. The results indicate that men were significantly more likely than women to allow their dogs to roam and to move their dogs. The current low vaccination rate of 12% highlighted the limited veterinary services that would need to be substantially increased to achieve effective rabies control. Participation in mass vaccination was accepted by 100% of the respondents. There was lower acceptance for other possible rabies control strategies with 10-20% of the respondents stating a resistance to both a mass culling program and a ban on dog movements. Consequently, movement bans and mass dog culling would have limited effectiveness as a control strategy in the NPA community

  2. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

    Science.gov (United States)

    Kallenberg, K.; Summers, D. M.; Romero, C.; Taratuto, A.; Heinemann, U.; Breithaupt, M.; Varges, D.; Meissner, B.; Ladogana, A.; Schuur, M.; Haik, S.; Collins, S. J.; Jansen, Gerard H.; Stokin, G. B.; Pimentel, J.; Hewer, E.; Collie, D.; Smith, P.; Roberts, H.; Brandel, J. P.; van Duijn, C.; Pocchiari, M.; Begue, C.; Cras, P.; Will, R. G.; Sanchez-Juan, P.

    2009-01-01

    Several molecular subtypes of sporadic Creutzfeldt–Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt–Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt–Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Patients with sporadic Creutzfeldt–Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt–Jakob disease’ but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt–Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt–Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic

  3. Overview of incursions of Asian H5N1 subtype highly pathogenic avian influenza virus into Great Britain, 2005-2008.

    Science.gov (United States)

    Alexander, Dennis J; Manvell, Ruth J; Irvine, Richard; Londt, Brandon Z; Cox, Bill; Ceeraz, Vanessa; Banks, Jill; Browna, Ian H

    2010-03-01

    Since 2005 there have been five incursions into Great Britain of highly pathogenic avian influenza (HPAI) viruses of subtype H5N1 related to the ongoing global epizootic. The first incursion occurred in October 2005 in birds held in quarantine after importation from Taiwan. Two incursions related to wild birds: one involved a single dead whooper swan found in March 2006 in the sea off the east coast of Scotland, and the other involved 10 mute swans and a Canada goose found dead over the period extending from late December 2007 to late February 2008 on or close to a swannery on the south coast of England. The other two outbreaks occurred in commercial poultry in January 2007 and November 2007, both in the county of Suffolk. The first of these poultry outbreaks occurred on a large turkey farm, and there was no further spread. The second outbreak occurred on a free-range farm rearing turkeys, ducks, and geese and spread to birds on a second turkey farm that was culled as a dangerous contact. Viruses isolated from these five outbreaks were confirmed to be Asian H5N1 HPAI viruses; the quarantine outbreak was attributed to a clade 2.3 virus and the other four to clade 2.2 viruses. This article describes the outbreaks, their control, and the possible origins of the responsible viruses.

  4. Pontine hyperperfusion in sporadic hyperekplexia.

    Science.gov (United States)

    Vetrugno, Roberto; Mascalchi, Mario; Vella, Alessandra; Della Nave, Riccardo; Guerrini, Laura; Vattimo, Angelo; del Giudice, Emanuele Miraglia; Plazzi, Giuseppe; D'Angelo, Roberto; Greco, Giovanni; Montagna, Pasquale

    2007-09-01

    To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H-MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. Both patients showed excessively large and non-habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H-MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals.

  5. Transmission dynamics and changing epidemiology of West Nile virus.

    Science.gov (United States)

    Blitvich, Bradley J

    2008-06-01

    West Nile virus (WNV) is a flavivirus that is maintained in a bird-mosquito transmission cycle. Humans, horses and other non-avian vertebrates are usually incidental hosts, but evidence is accumulating that this might not always be the case. Historically, WNV has been associated with asymptomatic infections and sporadic disease outbreaks in humans and horses in Africa, Europe, Asia and Australia. However, since 1994, the virus has caused frequent outbreaks of severe neuroinvasive disease in humans and horses in Europe and the Mediterranean Basin. In 1999, WNV underwent a dramatic expansion of its geographic range, and was reported for the first time in the Western Hemisphere during an outbreak of human and equine encephalitis in New York City. The outbreak was accompanied by extensive and unprecedented avian mortality. Since then, WNV has dispersed across the Western Hemisphere and is now found throughout the USA, Canada, Mexico and the Caribbean, and parts of Central and South America. WNV has been responsible for >27,000 human cases, >25,000 equine cases and hundreds of thousands of avian deaths in the USA but, surprisingly, there have been only sparse reports of WNV disease in vertebrates in the Caribbean and Latin America. This review summarizes our current understanding of WNV with particular emphasis on its transmission dynamics and changing epidemiology.

  6. China and USA in the Pacific and the Caribbean: Whose Incursion, Whose Territory? A Brief Rejoinder to McElroy and Bai

    Directory of Open Access Journals (Sweden)

    Ron Crocombe

    2009-05-01

    Full Text Available The title of the article in Island Studies Journal by McElroy and Bai (2008 illustrates an inherent bias. It says that it is about China’s “incursion” into the Caribbean and Pacific. The Oxford on-line dictionary’s main definition of incursion is “an invasion or attack, especially a sudden or brief one”; and my Collins dictionary gives its main definition as: “a sudden invasion, attack or raid.” Since there has never been any invasion, attack or raid (and therefore no incursion by China into the Pacific or the Caribbean, why do the authors imply that there is? In contrast, there have been plenty of “invasions, attacks and raids” by the USA in the Pacific Islands and the Caribbean during the past 150 years.

  7. Inheritable and sporadic non-autoimmune hyperthyroidism.

    Science.gov (United States)

    Ferraz, Carolina; Paschke, Ralf

    2017-03-01

    Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  8. Sporadic-E and spread-F in high latitude region

    International Nuclear Information System (INIS)

    Tao, Kazuhiko

    1974-01-01

    The heretofore made morphological studies of sporadic-E and spread-F as the typical irregularities of electron density are reviewed. These phenomena have close correlation with other geophysical phenomena which occur in the atmosphere of superhigh altitude in high latitude region. Many of these phenomena occur from same causes. Although the quantitative data are insufficient, the sporadic-E and spread-F in high latitude region are supposed to be caused by the precipitating charged particles falling from magnetosphere. A system, which can observe such phenomena simultaneously using the measuring instruments carried by satellites in the atmosphere of high altitude over high latitude region, is desirable to solve such problems. In detail, the morphological study on sporadic-E obtained from the observation of vertically projected ionosphere and the morphological study on sporadic-E from the observation of forward scattering and slanting entrance are reviewed. The correlation of the occurrence frequency of sporadic-E with solar activity, geomagnetic activity and other phenomena was studied. The morphological study on spread-F occurrence is reviewed. The observation of the spread-F in high latitude region by the application of top side sounding is reviewed. The correlation of the sporadic-E and spread-F in high latitude region with other geophysical phenomena is discussed. Finally, the discrete phenomenon and the diffuse phenomenon are discussed too. (Iwakiri, K.)

  9. Sporadic potassium layers and their connection to sporadic E layers in the mesopause region at Beijing, China

    Directory of Open Access Journals (Sweden)

    Jing Jiao

    2017-06-01

    Full Text Available A double-laser beam lidar to measure potassium (K layer at Beijing (40.5° N, 116.2° E was successfully developed in 2010. The parameters of sporadic Ks layers and their distributions were given. The seasonal distribution of Ks occurrence frequency was obtained, with two maxima in July and January. The seasonal distributions of sporadic Es layer occurrence frequency over Beijing differ from those of Ks. However, the good correlation between Es and Ks in the case-by-case studies supports the mechanism of neutralization of metal ions in a descending Es layer.

  10. The Prion Protein Preference of Sporadic Creutzfeldt-Jakob Disease Subtypes*

    Science.gov (United States)

    Klemm, Helen M. J.; Welton, Jeremy M.; Masters, Colin L.; Klug, Genevieve M.; Boyd, Alison; Hill, Andrew F.; Collins, Steven J.; Lawson, Victoria A.

    2012-01-01

    Sporadic Creutzfeldt-Jakob disease (CJD) is the most prevalent manifestation of the transmissible spongiform encephalopathies or prion diseases affecting humans. The disease encompasses a spectrum of clinical phenotypes that have been correlated with molecular subtypes that are characterized by the molecular mass of the protease-resistant fragment of the disease-related conformation of the prion protein and a polymorphism at codon 129 of the gene encoding the prion protein. A cell-free assay of prion protein misfolding was used to investigate the ability of these sporadic CJD molecular subtypes to propagate using brain-derived sources of the cellular prion protein (PrPC). This study confirmed the presence of three distinct sporadic CJD molecular subtypes with PrPC substrate requirements that reflected their codon 129 associations in vivo. However, the ability of a sporadic CJD molecular subtype to use a specific PrPC substrate was not determined solely by codon 129 as the efficiency of prion propagation was also influenced by the composition of the brain tissue from which the PrPC substrate was sourced, thus indicating that nuances in PrPC or additional factors may determine sporadic CJD subtype. The results of this study will aid in the design of diagnostic assays that can detect prion disease across the diversity of sporadic CJD subtypes. PMID:22930754

  11. Serum uric acid and lipid profiles in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Chen, Shuai; He, Shuang; Shang, Jun-Kui; Ma, Ming-Ming; Xu, Chang-Shui; Shi, Xiao-Hong; Zhang, Jie-Wen

    2016-02-01

    Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system. Brain lipid homeostasis and oxidative stress seem to play an important role in the disease pathogenesis. But little was known whether serum lipids and uric acid (a natural antioxidant) levels changed in patients with prion disease. Here we retrospectively reviewed and compared the serum lipids and uric acid levels of 19 probable sporadic CJD patients and 26 healthy control subjects. We found that the serum uric acid levels in sporadic CJD patients were significantly lower than that in controls (P=0.01). Serum triglycerides, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and apolipoprotein A1 (ApoA1) were similar in sporadic CJD patients and controls. However, LDL/HDL ratio was lower in sporadic CJD patients (P=0.003). The low serum uric acid and LDL/HDL ratio levels in sporadic CJD indicate that dysfunction in the lipid homeostasis and oxidative stress is associated with sporadic prion disease. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas

    OpenAIRE

    Chan, Sock Hoai; Lim, Weng Khong; Ishak, Nur Diana Binte; Li, Shao-Tzu; Goh, Wei Lin; Tan, Gek San; Lim, Kiat Hon; Teo, Melissa; Young, Cedric Ng Chuan; Malik, Simeen; Tan, Mann Hong; Teh, Jonathan Yi Hui; Chin, Francis Kuok Choon; Kesavan, Sittampalam; Selvarajan, Sathiyamoorthy

    2017-01-01

    Associations of sarcoma with inherited cancer syndromes implicate genetic predisposition in sarcoma development. However, due to the apparently sporadic nature of sarcomas, little attention has been paid to the role genetic susceptibility in sporadic sarcoma. To address this, we performed targeted-genomic sequencing to investigate the prevalence of germline mutations in known cancer-associated genes within an Asian cohort of sporadic sarcoma patients younger than 50 years old. We observed 13....

  13. Impaired proteasome function in sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; Agar, Jeffrey N; Strong, Michael J; Durham, Heather D

    2012-06-01

    Abstract The ubiquitin-proteasome system, important for maintaining protein quality control, is compromised in experimental models of familial ALS. The objective of this study was to determine if proteasome function is impaired in sporadic ALS. Proteasomal activities and subunit composition were evaluated in homogenates of spinal cord samples obtained at autopsy from sporadic ALS and non-neurological control cases, compared to cerebellum as a clinically spared tissue. The level of 20S α structural proteasome subunits was assessed in motor neurons by immunohistochemistry. Catalysis of peptide substrates of the three major proteasomal activities was substantially reduced in ALS thoracic spinal cord, but not in cerebellum, accompanied by alterations in the constitutive proteasome machinery. Chymotrypsin-like activity was decreased to 60% and 65% of control in ventral and dorsal spinal cord, respectively, concomitant with reduction in the β5 subunit with this catalytic activity. Caspase- and trypsin-like activities were reduced to a similar extent (46% - 68% of control). Proteasome levels, although generally maintained, appeared reduced specifically in motor neurons by immunolabelling. In conclusion, there are commonalities of findings in sporadic ALS patients and presymptomatic SOD1-G93A transgenic mice and these implicate inadequate proteasome function in the pathogenesis of both familial and sporadic ALS.

  14. Dietary factors and microsatellite instability in sporadic colon carcinomas

    NARCIS (Netherlands)

    Diergaarde, B.; Braam, H.; Muijen, van G.N.P.; Ligtenberg, M.J.L.; Kok, F.J.; Kampman, E.

    2003-01-01

    Microsatellite instability (MSI) occurs in 10-20% of the sporadic colon carcinomas and appears to be primarily due to alterations in hMLH1 and hMSH2. Little is known about the role of diet in MSI-related colon carcinogenesis. We used data from a Dutch population-based case-control study on sporadic

  15. Dietary factors and microsatellite instability in sporadic colon carcinomas.

    NARCIS (Netherlands)

    Diergaarde, B.; Braam, H.; Muijen, G.N.P. van; Ligtenberg, M.J.L.; Kok, F.J.; Kampman, E.

    2003-01-01

    Microsatellite instability (MSI) occurs in 10-20% of the sporadic colon carcinomas and appears to be primarily due to alterations in hMLH1 and hMSH2. Little is known about the role of diet in MSI-related colon carcinogenesis. We used data from a Dutch population-based case-control study on sporadic

  16. Visual art therapy in sporadic Creutzfeldt-Jakob disease: a case study.

    Science.gov (United States)

    Shrestha, Rajeet; Trauger-Querry, Barbara; Loughrin, Athena; Appleby, Brian S

    2016-01-01

    This paper describes the diagnostic and treatment utility of visual art therapy in a case of sporadic Creutzfeldt-Jakob disease. Visual art therapy was compared longitudinally with clinical and neuroimaging data over five-month period in an autopsy-confirmed case of sporadic Creutzfeldt-Jakob disease of MM2-cortical subtype. Art therapy sessions and content were useful in ascertaining neuropsychiatric symptoms during the course of her illness. Art therapy offered a unique emotional and cognitive outlet as illness progressed. Patients and families affected by sporadic Creutzfeldt-Jakob disease may benefit from art therapy despite the rapidly progressive nature of the illness. Art therapy can also be useful for assessment of patients with sporadic Creutzfeldt-Jakob disease by healthcare professionals.

  17. Marine incursion: the freshwater herring of Lake Tanganyika are the product of a marine invasion into west Africa.

    Directory of Open Access Journals (Sweden)

    Anthony B Wilson

    Full Text Available The spectacular marine-like diversity of the endemic fauna of Lake Tanganyika, the oldest of the African Great Lakes, led early researchers to suggest that the lake must have once been connected to the ocean. Recent geophysical reconstructions clearly indicate that Lake Tanganyika formed by rifting in the African subcontinent and was never directly linked to the sea. Although the Lake has a high proportion of specialized endemics, the absence of close relatives outside Tanganyika has complicated phylogeographic reconstructions of the timing of lake colonization and intralacustrine diversification. The freshwater herring of Lake Tanganyika are members of a large group of pellonuline herring found in western and southern Africa, offering one of the best opportunities to trace the evolutionary history of members of Tanganyika's biota. Molecular phylogenetic reconstructions indicate that herring colonized West Africa 25-50MYA, at the end of a major marine incursion in the region. Pellonuline herring subsequently experienced an evolutionary radiation in West Africa, spreading across the continent and reaching East Africa's Lake Tanganyika during its early formation. While Lake Tanganyika has never been directly connected with the sea, the endemic freshwater herring of the lake are the descendents of an ancient marine incursion, a scenario which may also explain the origin of other Tanganyikan endemics.

  18. Legionnaires’ Disease: Clinicoradiological Comparison of Sporadic Versus Outbreak Cases

    Directory of Open Access Journals (Sweden)

    Hafiz Rizwan Talib Hashmi

    2017-06-01

    Full Text Available Background: In 2015, New York City experienced the worst outbreak of Legionnaires’ disease in the history of the city. We compare patients seen during the 2015 outbreak with sporadic cases of Legionella during the past 5 years. Methods: We conducted a retrospective chart review of 90 patients with Legionnaires’ disease, including sporadic cases of Legionella infection admitted from 2010 to 2015 (n = 55 and cases admitted during the 2015 outbreak (n = 35. Results: We saw no significant differences between the 2 groups regarding demographics, smoking habits, alcohol intake, underlying medical disease, or residence type. Univariate and multivariate analyses showed that patients with sporadic case of Legionella had a longer stay in the hospital and intensive care unit as well as an increased stay in mechanical ventilation. Short-term mortality, discharge disposition, and most clinical parameters did not differ significantly between the 2 groups. Conclusions: We found no specific clinicoradiological characteristics that could differentiate sporadic from epidemic cases of Legionella . Early recognition and high suspicion for Legionnaires’ disease are critical to provide appropriate treatment. Cluster of cases should increase suspicion for an outbreak.

  19. Contrasting safety assessments of a runway incursion scenario: Event sequence analysis versus multi-agent dynamic risk modelling

    International Nuclear Information System (INIS)

    Stroeve, Sybert H.; Blom, Henk A.P.; Bakker, G.J.

    2013-01-01

    In the safety literature it has been argued, that in a complex socio-technical system safety cannot be well analysed by event sequence based approaches, but requires to capture the complex interactions and performance variability of the socio-technical system. In order to evaluate the quantitative and practical consequences of these arguments, this study compares two approaches to assess accident risk of an example safety critical sociotechnical system. It contrasts an event sequence based assessment with a multi-agent dynamic risk model (MA-DRM) based assessment, both of which are performed for a particular runway incursion scenario. The event sequence analysis uses the well-known event tree modelling formalism and the MA-DRM based approach combines agent based modelling, hybrid Petri nets and rare event Monte Carlo simulation. The comparison addresses qualitative and quantitative differences in the methods, attained risk levels, and in the prime factors influencing the safety of the operation. The assessments show considerable differences in the accident risk implications of the performance of human operators and technical systems in the runway incursion scenario. In contrast with the event sequence based results, the MA-DRM based results show that the accident risk is not manifest from the performance of and relations between individual human operators and technical systems. Instead, the safety risk emerges from the totality of the performance and interactions in the agent based model of the safety critical operation considered, which coincides very well with the argumentation in the safety literature.

  20. Assessing the Risk of a Canine Rabies Incursion in Northern Australia

    Science.gov (United States)

    Hudson, Emily G.; Brookes, Victoria J.; Ward, Michael P.

    2017-01-01

    Rabies is a globally distributed virus that causes approximately 60,00 human deaths annually with >99% of cases caused by dog bites. Australia is currently canine rabies free. However, the recent eastward spread of rabies in the Indonesian archipelago has increased the probability of rabies entry into northern Australian communities. In addition, many northern Australian communities have large populations of free-roaming dogs, capable of maintaining rabies should an incursion occur. A risk assessment of rabies entry and transmission into these communities is needed to target control and surveillance measures. Illegal transportation of rabies-infected dogs via boat landings is a high-risk entry pathway and was the focus of the current study. A quantitative, stochastic, risk assessment model was developed to evaluate the risk of rabies entry into north-west Cape York Peninsula, Australia, and rabies introduction to resident dogs in one of the communities via transport of rabies-infected dogs on illegal Indonesian fishing boats. Parameter distributions were derived from expert opinion, literature, and analysis of field studies. The estimated median probability of rabies entry into north-west Cape York Peninsula and into Seisia from individual fishing boats was 1.9 × 10−4/boat and 8.7 × 10−6/boat, respectively. The estimated annual probability that at least one rabies-infected dog enters north-west Cape York Peninsula and into Seisia was 5.5 × 10−3 and 3.5 × 10−4, respectively. The estimated median probability of rabies introduction into Seisia was 4.7 × 10−8/boat, and the estimated annual probability that at least one rabies-infected dog causes rabies transmission in a resident Seisia dog was 8.3 × 10−5. Sensitivity analysis using the Sobol method highlighted some parameters as influential, including but not limited to the prevalence of rabies in Indonesia, the probability of a dog on board an Indonesian fishing boat, and the

  1. Assessing the Risk of a Canine Rabies Incursion in Northern Australia

    Directory of Open Access Journals (Sweden)

    Emily G. Hudson

    2017-08-01

    Full Text Available Rabies is a globally distributed virus that causes approximately 60,00 human deaths annually with >99% of cases caused by dog bites. Australia is currently canine rabies free. However, the recent eastward spread of rabies in the Indonesian archipelago has increased the probability of rabies entry into northern Australian communities. In addition, many northern Australian communities have large populations of free-roaming dogs, capable of maintaining rabies should an incursion occur. A risk assessment of rabies entry and transmission into these communities is needed to target control and surveillance measures. Illegal transportation of rabies-infected dogs via boat landings is a high-risk entry pathway and was the focus of the current study. A quantitative, stochastic, risk assessment model was developed to evaluate the risk of rabies entry into north-west Cape York Peninsula, Australia, and rabies introduction to resident dogs in one of the communities via transport of rabies-infected dogs on illegal Indonesian fishing boats. Parameter distributions were derived from expert opinion, literature, and analysis of field studies. The estimated median probability of rabies entry into north-west Cape York Peninsula and into Seisia from individual fishing boats was 1.9 × 10−4/boat and 8.7 × 10−6/boat, respectively. The estimated annual probability that at least one rabies-infected dog enters north-west Cape York Peninsula and into Seisia was 5.5 × 10−3 and 3.5 × 10−4, respectively. The estimated median probability of rabies introduction into Seisia was 4.7 × 10−8/boat, and the estimated annual probability that at least one rabies-infected dog causes rabies transmission in a resident Seisia dog was 8.3 × 10−5. Sensitivity analysis using the Sobol method highlighted some parameters as influential, including but not limited to the prevalence of rabies in Indonesia, the probability of a dog on board an Indonesian

  2. Sporadic colorectal polyps and mismatch repair proteins

    Directory of Open Access Journals (Sweden)

    Mahsa Molaei

    2011-01-01

    Full Text Available Background: Colorectal cancers often arise from benign polyps. Adenomatous polyps and serrated polyps progress step by step to adenocarcinoma and change into malignant cancers. Genetic and epigenetic changes have correlation with specific stages of polyp-adenocarcinoma progression and colorectal cancer histopathological changes. Aims: In this study we used immunohistochemistry (IHC staining in sporadic colorectal polyps to assay functional status of MLH1, MSH2, MSH6, and PMS2 proteins, to track genetic/epigenetic roles of this issue in our patients. Materials and Methods: In this cross-sectional study we assessed all patients who were admitted with sporadic colorectal polyps and underwent polypectomy in endoscopy department during 2004-2008. Result: IHC results were abnormal in 6.8% cases for MLH1, in 4.5% cases for MSH2, in 3% for MSH6, and in 4.8% for PMS2. In all cases with abnormal PMS2, MLH1 was also reported as abnormal. Same results were reported for abnormal MSH2, which is accompanied with abnormal MSH6 in all cases (P values < 0.001. There is no significant difference between IHC staining results, gender, dysplasia grade, adenomatous type, and invasion. On the other hand, there was significant difference between IHC staining results, polyp location, and mean age of patients. The same significant difference was between adenomatous polyps and serrated adenoma polyps by MLH1 and PMS2 (P values < 0.05. Conclusion: According to our findings, maybe MMR dysfunction is the cause of sporadic colorectal polyps in younger age and its increasing risk of dysplasia progression and malignancy progression is only in serrated adenoma. Sporadic polyps in left colon had a higher risk to progress to malignancies, and abnormal IHC staining for MLH1 and PMS2 in serrated polyps is much more than in other adenomatous polyps.

  3. White matter involvement in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Caverzasi, Eduardo; Mandelli, Maria Luisa; DeArmond, Stephen J; Hess, Christopher P; Vitali, Paolo; Papinutto, Nico; Oehler, Abby; Miller, Bruce L; Lobach, Irina V; Bastianello, Stefano; Geschwind, Michael D; Henry, Roland G

    2014-12-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (PCreutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean

  4. Los Angeles International Airport Runway Incursion Studies: Phase III--Center-Taxiway Simulation

    Science.gov (United States)

    Madson, Michael D.

    2004-01-01

    Phase III of the Los Angeles International Airport Runway Incursion Studies was conducted, under an agreement with HNTB Corporation, at the NASA Ames FutureFlight Central (FFC) facility in June 2003. The objective of the study was the evaluation of a new center-taxiway concept at LAX. This study is an extension of the Phase I and Phase II studies previously conducted at FFC. This report presents results from Phase III of the study, in which a center-taxiway concept between runways 25L and 25R was simulated and evaluated. Phase III data were compared objectively against the Baseline data. Subjective evaluations by participating LAX controllers were obtained with regard to workload, efficiency, and safety criteria. To facilitate a valid comparison between Baseline and Phase III data, the same scenarios were used for Phase III that were tested during Phases I and II. This required briefing participating controllers on differences in airport and airline operations between 2001 and today.

  5. The Role of Iron In Sporadic E Layers

    Science.gov (United States)

    Vondrak, T.; Woodcock, K. R. I.; Plane, J. M. C.

    Sporadic E layers in the lower thermosphere are mostly composed of metallic ions, of which Fe+ is the most abundant. Because dielectric recombination (Fe+ + elec- tron) is very slow, the lifetime of Fe+ above about 100 km is at least several days. However, below this height molecular ions such as FeO+, FeO2+ and FeN2+ form in- creasingly rapidly through reactions with O3, O2 and N2, respectively. These undergo rapid dissociative recombination with electrons, causing Fe+ to be neutralised increas- ingly rapidly as a sporadic E layer descends. Indeed, this is the most likely mechanism for the formation of the sporadic neutral Fe layers that are observed by lidar. However, atomic O plays a very important role in reducing these molecular ions back to Fe+, competing with dissociative recombination and thus slowing the rate at which Fe+ is neutralised and a sporadic E layer dissipates. This paper will discuss a laboratory and modelling study of the reactions of FeO+, FeO2+ and FeN2+ with atomic O. These reactions were studied (for the first time) in a fast flow tube, using the pulsed laser ablation of a rotating iron rod as the source of Fe+ ions in the upstream section of the tube. Reactants were then added to produce molecular ions, and atomic O further downstream through a movable injector. Fe+ and the molecular ions were detected at the downstream end of the tube using a two-stage quadrupole mass spectrometer. The spectroscopy of the FeO+ ion, observed by laser induced fluorescence, will also be discussed as a candidate for future ground-based lidar studies of the ion chemistry of the lower thermosphere.

  6. Sporadic simple groups and quotient singularities

    International Nuclear Information System (INIS)

    Cheltsov, I A; Shramov, C A

    2013-01-01

    We show that if a faithful irreducible representation of a central extension of a sporadic simple group with centre contained in the commutator subgroup gives rise to an exceptional (resp. weakly exceptional but not exceptional) quotient singularity, then that simple group is the Hall-Janko group (resp. the Suzuki group)

  7. Screening of hypoxia-inducible genes in sporadic ALS.

    LENUS (Irish Health Repository)

    Cronin, Simon

    2008-10-01

    Genetic variations in two hypoxia-inducible angiogenic genes, VEGF and ANG, have been linked with sporadic amyotrophic lateral sclerosis (SALS). Common variations in these genes may reduce the levels or functioning of their products. VEGF and ANG belong to a larger group of angiogenic genes that are up-regulated under hypoxic conditions. We hypothesized that common genetic variation across other members of this group may also predispose to sporadic ALS. To screen other hypoxia-inducible angiogenic genes for association with SALS, we selected 112 tagging single nucleotide polymorphisms (tgSNPs) that captured the common genetic variation across 16 VEGF-like and eight ANG-like hypoxia-inducible genes. Screening for association was performed in 270 Irish individuals with typical SALS and 272 ethnically matched unrelated controls. SNPs showing association in the Irish phase were genotyped in a replication sample of 281 Swedish sporadic ALS patients and 286 Swedish controls. Seven markers showed association in the Irish. The one modest replication signal observed in the Swedish replication sample, at rs3801158 in the gene inhibin beta A, was for the opposite allele vs. the Irish cohort. We failed to detect association of common variation across 24 candidate hypoxia-inducible angiogenic genes with SALS.

  8. Epidemic Spread of Usutu Virus in Southwest Germany in 2011 to 2013 and Monitoring of Wild Birds for Usutu and West Nile Viruses.

    Science.gov (United States)

    Ziegler, Ute; Jöst, Hanna; Müller, Kerstin; Fischer, Dominik; Rinder, Monika; Tietze, Dieter Thomas; Danner, Klaus-Jürgen; Becker, Norbert; Skuballa, Jasmin; Hamann, Hans-Peter; Bosch, Stefan; Fast, Christine; Eiden, Martin; Schmidt-Chanasit, Jonas; Groschup, Martin H

    2015-08-01

    Mosquito-borne viruses are becoming an increasing threat for Europe. One of these viruses is Usutu virus (USUV), a single-stranded RNA virus belonging to the Japanese encephalitis virus group within the family Flaviviridae. Since the occurrence of USUV among wild birds in June, 2011, infected Blackbirds (Turdus merula) have frequently been found dead in southwest Germany, cumulating in a massive die-off. Moreover, other bird species (Strigiformes) in this region have been affected. In a first study, 209 of over 600 dead birds (wild birds and birds kept in aviaries) collected from 2011 to 2013 carried USUV, more than 88% of them Blackbirds. USUV had already been detected in 2010, one year before the epizooty, in a mosquito-based surveillance program in Germany. The main epidemic area of the USUV outbreak in wild birds in southwest Germany has been similar for the last three years. In a second study during 2011 to 2013, 902 live migratory and resident birds (representing 87 bird species belonging to 14 bird orders) from four different sampling sites were bled and tested serologically and by qPCR for West Nile virus (WNV) and USUV infections. No USUV or WNV genomes were detected. Some migratory birds (mainly long-distance migrants and some partial migrants) carried neutralizing antibodies against WNV as discriminated by USUV and WNV cross-neutralization tests. Only few resident birds showed relevant USUV-specific neutralizing antibodies. The occurrence of USUV in the Upper Rhine valley area of southwest Germany is a proof of principle for the incursion and spread of other arthropod-borne (arbo)-viruses along these routes. Therefore, monitoring studies in birds and mosquitoes for the presence of arboviruses in these areas are indispensable.

  9. Early Detection of Sporadic Pancreatic Cancer

    Science.gov (United States)

    Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

    2015-01-01

    Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

  10. Magnetic resonance spectroscopic abnormalities in sporadic and variant Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Pandya, H.G.; Coley, S.C.; Wilkinson, I.D.; Griffiths, P.D.

    2003-01-01

    AIM: To study the proton MR spectroscopic findings in Creutzfeldt-Jakob disease (CJD) (sporadic and variant). MATERIALS AND METHODS: MR imaging and proton MR spectra were acquired in two patients with sporadic CJD (biopsy proven) and one patient with variant CJD. RESULTS: The two patients with sporadic CJD demonstrated MR signal change within the basal ganglia and thalami and reduced N-acetylaspartate (NAA):creatine ratios. The patient with variant CJD showed characteristic signal change within the pulvinar of the thalami and a markedly reduced N-acetylaspartate:creatine ratio. CONCLUSION: All three patients with CJD demonstrated evidence of reduced N-acetylaspartate: creatine ratios on MR spectroscopy. These changes imply that neuronal loss and/or dysfunction is a consistent finding in established CJD. Pandya H. G., et al (2003) Clinical Radiology58, 148--153

  11. Magnetic resonance spectroscopic abnormalities in sporadic and variant Creutzfeldt-Jakob disease

    Energy Technology Data Exchange (ETDEWEB)

    Pandya, H.G.; Coley, S.C.; Wilkinson, I.D.; Griffiths, P.D

    2003-02-01

    AIM: To study the proton MR spectroscopic findings in Creutzfeldt-Jakob disease (CJD) (sporadic and variant). MATERIALS AND METHODS: MR imaging and proton MR spectra were acquired in two patients with sporadic CJD (biopsy proven) and one patient with variant CJD. RESULTS: The two patients with sporadic CJD demonstrated MR signal change within the basal ganglia and thalami and reduced N-acetylaspartate (NAA):creatine ratios. The patient with variant CJD showed characteristic signal change within the pulvinar of the thalami and a markedly reduced N-acetylaspartate:creatine ratio. CONCLUSION: All three patients with CJD demonstrated evidence of reduced N-acetylaspartate: creatine ratios on MR spectroscopy. These changes imply that neuronal loss and/or dysfunction is a consistent finding in established CJD. Pandya H. G., et al (2003) Clinical Radiology58, 148--153.

  12. Cervical dystonia: about familial and sporadic cases in 88 patients

    Directory of Open Access Journals (Sweden)

    Carlos Henrique F. Camargo

    2014-02-01

    Full Text Available Cervical dystonia (CD affects the musculature of the neck in a focal way or associated to other parts of the body. The aim of this study was to identify clinical differences between patients with dystonia patients without family history and with family history (sporadic. Eighty-eight patients with CD were recruited in a Movement Disorders Clinic between June of 2008 and June of 2009. Only patients with no etiological diagnosis were accepted for analysis. The age of onset of symptoms was later in patients with focal and segmental dystonia than in patients with generalized dystonia (p<0.001. The severity of symptoms was higher in patients with sporadic dystonia than in familial patients (p<0.01. Generalized cases were more severe in patients with a family history (p<0.01. Sporadic patients had higher levels of pain than familial cases (p<0.05. We expect soon to present the results of genetic analyzes of these patients.

  13. Genetic Relatedness among Nontypeable Pneumococci Implicated in Sporadic Cases of Conjunctivitis

    OpenAIRE

    Barker, Jason H.; Musher, Daniel M.; Silberman, Ronald; Phan, Hoang M.; Watson, David A.

    1999-01-01

    Nontypeable Streptococcus pneumoniae is a common cause of epidemic conjunctivitis. A previous molecular fingerprinting study identified a clone of nontypeable pneumococcus that was responsible for a recent outbreak of conjunctivitis. In the present study, we examined the extent to which pneumococci that cause sporadic cases of conjunctivitis are related to this epidemic strain. Using arbitrarily primed BOX-PCR, we have determined that, of 10 nontypeable pneumococci causing sporadic conjunctiv...

  14. Difference in aneurysm characteristics between patients with familial and sporadic aneurysmal subarachnoid haemorrhage

    NARCIS (Netherlands)

    Mensing, Liselore A.; Rinkel, Gabriel J E; Vlak, Monique H M; Van Der Schaaf, Irene C.; Ruigrok, Ynte M.

    2016-01-01

    Object Patients with familial intracranial aneurysms (IA) have a higher risk of rupture than patients with sporadic IA. We compared geometric and morphological risk factors for aneurysmal rupture between patients with familial and sporadic aneurysmal subarachnoid hemorrhage (aSAH) to analyse if

  15. Molecular pathogenesis of sporadic prion diseases in man

    Science.gov (United States)

    Safar, Jiri G.

    2012-01-01

    The yeast, fungal and mammalian prions determine heritable and infectious traits that are encoded in alternative conformations of proteins. They cause lethal sporadic, familial and infectious neurodegenerative conditions in man, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic (s)CJD. Recent advances in amplification and detection of prions led to considerable optimism that early and possibly preclinical diagnosis and therapy might become a reality. Although several drugs have already been tested in small numbers of sCJD patients, there is no clear evidence of any agent’s efficacy. Therefore, it remains crucial to determine the full spectrum of sCJD prion strains and the conformational features in the pathogenic human prion protein governing replication of sCJD prions. Research in this direction is essential for the rational development of diagnostic as well as therapeutic strategies. Moreover, there is growing recognition that fundamental processes involved in human prion propagation – intercellular induction of protein misfolding and seeded aggregation of misfolded host proteins – are of far wider significance. This insight leads to new avenues of research in the ever-widening spectrum of age-related human neurodegenerative diseases that are caused by protein misfolding and that pose a major challenge for healthcare. PMID:22421210

  16. Re-Evaluating the Geological Evidence for Late Holocene Marine Incursion Events along the Guerrero Seismic Gap on the Pacific Coast of Mexico.

    Directory of Open Access Journals (Sweden)

    Thomas A Bianchette

    Full Text Available Despite the large number of tsunamis that impact Mexico's Pacific coast, stratigraphic studies focusing on geological impacts are scanty, making it difficult to assess the long-term risks for this vulnerable region. Surface samples and six cores were taken from Laguna Mitla near Acapulco to examine sedimentological and geochemical evidence for marine incursion events. Sediment cores collected from behind the beach barrier are dominated by intercalated layers of peat and inorganic sediments, mostly silt and clay, with little or no sand. Sand- and shell-rich clastic layers with high levels of sulfur, calcium, and strontium only occur adjacent to the relict beach ridge remnants near the center of the lagoon. With the exception of one thin fine sand layer, the absence of sand in the near-shore cores and the predominance of the terrigenous element titanium in the inorganic layers, evidently eroded from the surrounding hillslopes, suggests that these large-grained intervals do not represent episodic marine incursions, but rather were likely formed by the erosion and redeposition of older marine deposits derived from the beach ridge remnants when water levels were high. These results do not support the occurrence of a large tsunami event at Laguna Mitla during the Late Holocene.

  17. Re-Evaluating the Geological Evidence for Late Holocene Marine Incursion Events along the Guerrero Seismic Gap on the Pacific Coast of Mexico.

    Science.gov (United States)

    Bianchette, Thomas A; McCloskey, Terrence A; Liu, Kam-Biu

    2016-01-01

    Despite the large number of tsunamis that impact Mexico's Pacific coast, stratigraphic studies focusing on geological impacts are scanty, making it difficult to assess the long-term risks for this vulnerable region. Surface samples and six cores were taken from Laguna Mitla near Acapulco to examine sedimentological and geochemical evidence for marine incursion events. Sediment cores collected from behind the beach barrier are dominated by intercalated layers of peat and inorganic sediments, mostly silt and clay, with little or no sand. Sand- and shell-rich clastic layers with high levels of sulfur, calcium, and strontium only occur adjacent to the relict beach ridge remnants near the center of the lagoon. With the exception of one thin fine sand layer, the absence of sand in the near-shore cores and the predominance of the terrigenous element titanium in the inorganic layers, evidently eroded from the surrounding hillslopes, suggests that these large-grained intervals do not represent episodic marine incursions, but rather were likely formed by the erosion and redeposition of older marine deposits derived from the beach ridge remnants when water levels were high. These results do not support the occurrence of a large tsunami event at Laguna Mitla during the Late Holocene.

  18. Radio tomographic imaging of sporadic-E layers during SEEK-2

    Directory of Open Access Journals (Sweden)

    P. A. Bernhardt

    2005-10-01

    Full Text Available During the SEEK-2 Rocket Campaign in August 2002, a Dual Band Beacon (DBB transmitting to Ground Receivers provided unique data on E-Region electron densities. Information from two rocket beacons and four ground receivers yielded multiple samples of E-region horizontal and vertical variations. The radio beacon measurements were made at four sites (Uchinoura, Tarumizu, Tanegashima, Takazaki in Japan for two rockets (S310-31 and S310-32 launched by the Institute of Space and Aeronautical Science (ISAS. Analysis was completed for four sets of beacon data to provide electron density images of sporadic-E layers. Signals from the two-frequency beacons on the SEEK-2 rockets were processed to yield total electron content (TEC data that was converted into electron density measurements. Wide variations in layer structures were detected. These included horizontal sporadic-E variations, vertical profiles of double, single, and weak layers. The radio beacon measurements were shown to be in agreement with the in-situ SEEK-2 sensors. The first tomographic image of a sporadic-E layer was produced from the data. The rocket beacon technique was shown to be an excellent tool to study sporadic-E layers because absolute TEC accuracy of 0.01 TEC Units can be easily obtained and, with proper receiver placement, electron density images can be produced using computerized ionospheric tomography with better than 1km horizontal and vertical resolution. Keywords. Ionospheric irregularities – Instruments and techniques – Mid-latitude ionosphere

  19. Can the TLR-4-Mediated Signaling Pathway Be “A Key Inflammatory Promoter for Sporadic TAA”?

    Directory of Open Access Journals (Sweden)

    Giovanni Ruvolo

    2014-01-01

    Full Text Available Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR and medial degeneration (MD occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR- 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR=14.4, P=0.0008 and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

  20. PRKAG3 polymorphisms associated with sporadic Wolff–Parkinson–White syndrome among a Taiwanese population

    Directory of Open Access Journals (Sweden)

    Ken-Pen Weng

    2016-12-01

    Conclusion: This study shows that PRKAG3-230 may be associated with sporadic WPW syndrome among a Taiwanese population. Further studies are warranted to elucidate the role of mutations in AMPK subunit genes other than PRKAG3-230 in sporadic WPW syndrome.

  1. An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis

    Directory of Open Access Journals (Sweden)

    Melissa S Rotunno

    2013-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder that targets motor neurons, leading to paralysis and death within a few years of disease onset. While several genes have been linked to the inheritable, or familial, form of ALS, much less is known about the cause(s of sporadic ALS, which accounts for approximately 90% of ALS cases. Due to the clinical similarities between familial and sporadic ALS, it is plausible that both forms of the disease converge on a common pathway and, therefore, involve common factors. Recent evidence suggests the Cu,Zn-superoxide dismutase (SOD1 protein to be one such factor that is common to both sporadic and familial ALS. In 1993, mutations were uncovered in SOD1 that represent the first known genetic cause of familial ALS. While the exact mechanism of mutant-SOD1 toxicity is still not known today, most evidence points to a gain of toxic function that stems, at least in part, from the propensity of this protein to misfold. In the wild-type SOD1 protein, non-genetic perturbations such as metal depletion, disruption of the quaternary structure, and oxidation, can also induce SOD1 to misfold. In fact, these aforementioned post-translational modifications cause wild-type SOD1 to adopt a toxic conformation that is similar to familial ALS-linked SOD1 variants. These observations, together with the detection of misfolded wild-type SOD1 within human post-mortem sporadic ALS samples, have been used to support the controversial hypothesis that misfolded forms of wild-type SOD1 contribute to sporadic ALS pathogenesis. In this review, we present data from the literature that both support and contradict this hypothesis. We also discuss SOD1 as a potential therapeutic target for both familial and sporadic ALS.

  2. Thunderstorm related variations of the ionospheric sporadic E layer over Rome

    Science.gov (United States)

    Barta, Veronika; Scotto, Carlo; Pietrella, Marco

    2013-04-01

    Meteorological events in the lower atmosphere can affect the ionosphere by electromagnetic and mechanical processes. One type of the latter ones is the internal atmospheric gravity waves (AGWs) which can often be generated by thunderstorms. According to a Superposed Epoch Analyses (SEA) using the time series of the critical frequency (foEs) and virtual height (h'Es) of the sporadic E layer and WWLLN (World Wide Lightning Location Network) lightning data over the ionospheric station of Rome (41.9° 12.5°) there is a statistically significant decrease in the foEs of the sporadic E layer after the time of the lightnings. This may indicate a sudden decrease in the electron density of the sporadic E layer associated to lightnings. In order to understand the physical explanation for this phenomenon further studies are performed as follows: a SEA for different seasons and for daytime - nightime lightnings separately. Direction of arrival of thunderstorms is also taken into account.

  3. The genetics of radiation-induced and sporadic osteosarcoma: a unifying theory?

    International Nuclear Information System (INIS)

    Rosemann, Michael; Kuosaite, Virginija; Nathrath, Michaela; Atkinson, Michael J.

    2002-01-01

    Cancer is a disease of the genome, with the neoplastic phenotype being passed from one cell generation to the other. Radiation-induced cancer has often been considered to represent a unique entity amongst neoplasia, with the energy deposition being held responsible for both direct (gene mutations) and indirect (bystander effects, induced instability etc) alterations to the cellular genome. However, radiogenic tumours in man and experimental animals appear to be physiologically and genetically indistinguishable from their sporadic counterparts, suggesting that the aetiologies of these two tumour types are in fact closely related. We have conducted a general screen of the genetic alterations in radiation-induced mouse osteosarcoma, a tumour that is histopathologically indistinguishable from human sporadic osteosarcoma. Comparison of the two tumour types indicates the existence of a common set of genetic changes, providing additional evidence to support the concept that the molecular pathology of radiation-induced malignancy is no different to that of sporadic cancers. (author)

  4. Comparing Sporadic and Outbreak-associated Foodborne Illness

    Centers for Disease Control (CDC) Podcasts

    2016-11-04

    Dr. Eric Ebel, a veterinarian and risk analyst with USDA’s Food Safety and Inspection Service, discusses his article on sporadic and outbreak-associated cases of foodborne illness.  Created: 11/4/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/4/2016.

  5. Brain sonography in African infants with complicated sporadic ...

    African Journals Online (AJOL)

    Background: To determine the structural findings in brain sonography of African infants with complicated sporadic bacterial meningitis. Materials and Methods: Retrospective assessment of medical records of patients who underwent brain sonography on account of complicated bacterial meningitis. The brain sonography ...

  6. Seroprevalence and distribution of arboviral infections among rural Kenyan adults: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Schoepp Randal J

    2011-07-01

    Full Text Available Abstract Background Arthorpod-borne viruses (arboviruses cause wide-spread morbidity in sub-Saharan Africa, but little research has documented the burden and distribution of these pathogens. Methods Using a population-based, cross-sectional study design, we administered a detailed questionnaire and used ELISA to test the blood of 1,141 healthy Kenyan adults from three districts for the presence of anti-viral Immunoglobulin G (IgG antibodies to the following viruses: dengue (DENV, West Nile (WNV, yellow fever (YFV, Chikungunya (CHIKV, and Rift Valley fever (RVFV. Results Of these, 14.4% were positive for DENV, 9.5% were WNV positive, 9.2% were YFV positive, 34.0% were positive for CHIKV and 0.7% were RVFV positive. In total, 46.6% had antibodies to at least one of these arboviruses. Conclusions For all arboviruses, district of residence was strongly associated with seropositivity. Seroprevalence to YFV, DENV and WNV increased with age, while there was no correlation between age and seropositivity for CHIKV, suggesting that much of the seropositivity to CHIKV is due to sporadic epidemics. Paradoxically, literacy was associated with increased seropositivity of CHIKV and DENV.

  7. Observation of electron biteout regions below sporadic E layers at polar latitudes

    Directory of Open Access Journals (Sweden)

    G. A. Lehmacher

    2015-03-01

    Full Text Available The descent of a narrow sporadic E layer near 95 km altitude over Poker Flat Research Range in Alaska was observed with electron probes on two consecutive sounding rockets and with incoherent scatter radar during a 2 h period near magnetic midnight. A series of four trimethyl aluminum chemical releases demonstrated that the Es layer remained just slightly above the zonal wind node, which was slowly descending due to propagating long-period gravity waves. The location of the layer is consistent with the equilibrium position due to combined action of the wind shear and electric fields. Although the horizontal electric field could not be measured directly, we estimate that it was ~ 2 mV m−1 southward, consistent with modeling the vertical ion drift, and compatible with extremely quiet conditions. Both electron probes observed deep biteout regions just below the Es enhancements, which also descended with the sporadic layers. We discuss several possibilities for the cause of these depletions; one possibility is the presence of negatively charged, nanometer-sized mesospheric smoke particles. Such particles have recently been detected in the upper mesosphere, but not yet in immediate connection with sporadic E. Our observations of electron depletions suggest a new process associated with sporadic E.

  8. Genetic overlap between apparently sporadic motor neuron diseases

    NARCIS (Netherlands)

    van Blitterswijk, Marka; Vlam, Lotte; van Es, Michael A.; van der Pol, W.-Ludo; Hennekam, Eric A. M.; Dooijes, Dennis; Schelhaas, Helenius J.; van der Kooi, Anneke J.; de Visser, Marianne; Veldink, Jan H.; van den Berg, Leonard H.

    2012-01-01

    Progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS) are devastating motor neuron diseases (MNDs), which result in muscle weakness and/or spasticity. We compared mutation frequencies in genes known to be associated with MNDs between patients with apparently sporadic PMA and

  9. Neuroendocrine Differentiation in Sporadic CRC and Hereditary Nonpolyosis Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    M. H. Sun

    2004-01-01

    Full Text Available Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.

  10. Early Detection of Sporadic Pancreatic Cancer

    Science.gov (United States)

    Chari, Suresh T.; Kelly, Kimberly; Hollingsworth, Michael A.; Thayer, Sarah P.; Ahlquist, David A.; Andersen, Dana K.; Batra, Surinder K.; Brentnall, Teresa A.; Canto, Marcia; Cleeter, Deborah F.; Firpo, Matthew A.; Gambhir, Sanjiv Sam; Go, Vay Liang W.; Hines, O. Joe; Kenner, Barbara J.; Klimstra, David S.; Lerch, Markus M.; Levy, Michael J.; Maitra, Anirban; Mulvihill, Sean J.; Petersen, Gloria M.; Rhim, Andrew D.; Simeone, Diane M.; Srivastava, Sudhir; Tanaka, Masao; Vinik, Aaron I.; Wong, David

    2015-01-01

    Abstract Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC. PMID:25931254

  11. Genetic Relatedness among Nontypeable Pneumococci Implicated in Sporadic Cases of Conjunctivitis

    Science.gov (United States)

    Barker, Jason H.; Musher, Daniel M.; Silberman, Ronald; Phan, Hoang M.; Watson, David A.

    1999-01-01

    Nontypeable Streptococcus pneumoniae is a common cause of epidemic conjunctivitis. A previous molecular fingerprinting study identified a clone of nontypeable pneumococcus that was responsible for a recent outbreak of conjunctivitis. In the present study, we examined the extent to which pneumococci that cause sporadic cases of conjunctivitis are related to this epidemic strain. Using arbitrarily primed BOX-PCR, we have determined that, of 10 nontypeable pneumococci causing sporadic conjunctivitis, 5 were clonal and closely related to a previous outbreak strain, whereas 5 others were genetically diverse. PMID:10565927

  12. Mutation analysis for DJ-1 in sporadic and familial parkinsonism: screening strategy in parkinsonism.

    Science.gov (United States)

    Tomiyama, Hiroyuki; Li, Yuanzhe; Yoshino, Hiroyo; Mizuno, Yoshikuni; Kubo, Shin-Ichiro; Toda, Tatsushi; Hattori, Nobutaka

    2009-05-22

    DJ-1 mutations cause autosomal recessive parkinsonism (ARP). Although some reports of DJ-1 mutations have been published, there is lack of information on the prevalence of these mutations in large-scale studies of both familial and sporadic parkinsonism. In this genetic screening study, we analyzed the distribution and frequency of DJ-1 mutations by direct nucleotide sequencing of coding exons and exon-intron boundaries of DJ-1, in 386 parkin-negative parkinsonism patients (371 index cases: 67 probands of autosomal recessive parkinsonism families, 90 probands of autosomal dominant parkinsonism families, 201 patients with sporadic parkinsonism, and 13 with unknown family histories) from 12 countries (Japan 283, China 27, Taiwan 22, Korea 22, Israel 16, Turkey 5, Philippines 2, Bulgaria 2, Greece 2, Tunisia 1, USA 2, Ukraine 1, unknown 1). None had causative mutation in DJ-1, suggesting DJ-1 mutation is very rare among patients with familial and sporadic parkinsonism from Asian countries and those with other ethnic background. This is in contrast to the higher frequencies and worldwide distribution of parkin- and PINK1-related parkinsonism in ARP and sporadic parkinsonism. Thus, after obtaining clinical information, screening for mutations in (1) parkin, (2) PINK1, (3) DJ-1, (4) ATP13A2 should be conducted in that order, in ARP and sporadic parkinsonism, based on their reported frequencies. In addition, haplotype analysis should be employed to check for homozygosity of 1p36, which harbors a cluster of causative genes for ARP such as DJ-1, PINK1 and ATP13A2 in ARP and sporadic parkinsonism, especially in parkinsonism with consanguinity.

  13. Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.

    Science.gov (United States)

    Kobayashi, Atsushi; Parchi, Piero; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

    2016-06-01

    As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft-associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases. © 2015 Japanese Society of Neuropathology.

  14. Processes Underlying Rabies Virus Incursions across US-Canada Border as Revealed by Whole-Genome Phylogeography.

    Science.gov (United States)

    Trewby, Hannah; Nadin-Davis, Susan A; Real, Leslie A; Biek, Roman

    2017-09-01

    Disease control programs aim to constrain and reduce the spread of infection. Human disease interventions such as wildlife vaccination play a major role in determining the limits of a pathogen's spatial distribution. Over the past few decades, a raccoon-specific variant of rabies virus (RRV) has invaded large areas of eastern North America. Although expansion into Canada has been largely prevented through vaccination along the US border, several outbreaks have occurred in Canada. Applying phylogeographic approaches to 289 RRV whole-genome sequences derived from isolates collected in Canada and adjacent US states, we examined the processes underlying these outbreaks. RRV incursions were attributable predominantly to systematic virus leakage of local strains across areas along the border where vaccination has been conducted but also to single stochastic events such as long-distance translocations. These results demonstrate the utility of phylogeographic analysis of pathogen genomes for understanding transboundary outbreaks.

  15. Magnetic eta index and the ability to forecast sporadic E layer appearance

    Science.gov (United States)

    Dziak-Jankowska, Beata; Stanislawska, Iwona; Pozoga, Mariusz; Tomasik, Lukasz; Ernst, Tomasz

    2012-07-01

    We analysed the correlation of the changes of the magnetic vertical component with the ionospheric deviations from monthly median of the E layer characteristics. Promising results indicate that the eta parameter can be used to predict sporadic E layer during magnetically quiet days. Our previous work concern the data from only one year - 2004. During the descending phase of solar cycle in 2004 there was not numerous amount of quiet days. We extend our research to other years starting from 1996 and focusing on 2007 - 2009, years of the prolonged solar minimum. The analysis shows that under magnetically quiet circumstances the magnetic index eta indicates large magnetic disturbance, especially in vertical component when other magnetic indices inform about quiet magnetic conditions. The results indicate that the increase of the magnetic eta index (the ratio of the variations of vertical component of the external magnetic field to the horizontal component) is associated with the emergence of sporadic E layer or with increase of foEs critical frequency of sporadic E layer. The appearance of sporadic E layer followed 1-2 h after growth of magnetic index eta. An important conclusion is that the analysis of the hourly ionospheric data does not give 100% correlation between the increase of eta and the emergence of Es layer, however, studies of dense measurement data show that the correlation is almost 100%. An advantage of the eta index is the fact that after eliminating the effect of currents induced within the Earth, eta index bring independent and meaningful information on the system of current in the ionosphere. Hence, the eta index could be an important element of the ionosphere monitoring and can be used to predict such local phenomenon like the appearance of the sporadic E layer.

  16. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Daoud, H; Valdmanis, P N; Kabashi, E; Dion, P; Dupré, N; Camu, W; Meininger, V; Rouleau, G A

    2009-02-01

    Mutations in the TARDBP gene, which encodes the TAR DNA binding protein (TDP-43), have been described in individuals with familial and sporadic amyotrophic lateral sclerosis (ALS). We screened the TARDBP gene in 285 French sporadic ALS patients to assess the frequency of TARDBP mutations in ALS. Six individuals had potentially deleterious mutations of which three were novel including a Y374X truncating mutation and P363A and A382P missense mutations. This suggests that TARDBP mutations may predispose to ALS in approximately 2% of the individuals followed in this study. Our findings, combined with those from other collections, brings the total number of mutations in unrelated ALS patients to 17, further suggesting that mutations in the TARDBP gene have an important role in the pathogenesis of ALS.

  17. Holocene beach buildup and coastal aeolian sand incursions off the Nile littoral cell

    Science.gov (United States)

    Roskin, Joel; Sivan, Dorit; Shtienberg, Gilad; Porat, Naomi; Bookman, Revital

    2017-04-01

    Israel's coastal plain is abundant with sand originating from the Nile littoral cell. The inland windblown loose sand has formed 3-6 km wide lobe-like sand and dune fields currently comprised of foredunes, linear and northeasterly facing transverse and parabolic dunes that are currently stabilized by vegetation. This study reviews the architecture and history of the these dune fields aiming to: (a) Date the timings of beach accretion, and sand and dune incursions. (b) Discriminate between natural and human-induced forcing factors of sand mobilization and stabilization in time and space. (c) Present a model of the dunescape development. (d) Assess scenarios of sand transport in the future charcaterized by intense human impact and climate change. Luminescence ages, radiocarbon dates and relative ages from previously published geological and archaeological reports, historical texts, together with new optically stimulated luminescence (OSL) ages and stratigraphic and sedimentological data are analyzed. The deposition, mobilizations and preservation of the sand bodies, initially induced by the decline in sea level rise at 6-4 ka, were later controlled by historic land-use intensity and modern land-use/negligence practices. At 6 ka, beach sand buildup rapidly started. Where aeolianite ridges bordered the coast, pulses of sand with biogenic carbonate grains unconformably draped the ridges and rapidly consolidated into a distinct sandy calcarenite unit. Further east, sand sheets and low dunes partly pedogenized following their incursion, but did not cement. The water retention capacities of the sand sheets enabled the establishment of a sand-stabilizing vegetation cover that probably became an attractive environment for fuel and grazing. The growing Hellenistic-Roman-Byzantine ( 2.4-1.3 ka) populations probably led to increased consumption and massive destruction of sand stabilizing vegetation, enabling sand erodibility and mobilization during winter storms. The sand

  18. Prevalence of Abnormal Cervical Smears from Sporadic Screening ...

    African Journals Online (AJOL)

    The aim of the study was to find the prevalence of abnormal smears in an unscreened population of sexually active women attending a gynaecological clinic. “Pap” smears were taken sporadically for cytological examination from sexually active women attending gynaecological clinics at the Federal Medical Centre Gombe.

  19. MAJOR MOLECULAR GENETIC DRIVERS IN SPORADIC PRIMARY HYPERPARATHYROIDISM.

    Science.gov (United States)

    Arnold, Andrew

    2016-01-01

    Primary hyperparathyroidism is primarily due to a solitary parathyroid adenoma but multi-gland disease, parathyroid carcinoma, and ectopic parathyroid hormone production can occur. Although primary hyperparathyroidism mostly presents sporadically, strong familial predispositions also exist. Much is known about heritable genetic mutations responsible for these syndromes, including multiple endocrine neoplasia types 1 and 2A, hyperparathyroidism-jaw tumor syndrome, and familial hypocalciuric hypercalcemia. Acquired mutations in common sporadic hyperparathyroidism have also been discovered. Here we focus on the most common and well-established genetic drivers: 1) involvement of the oncogene cyclin D1 in human neoplasia was first established in parathyroid adenomas, followed by recognition of its importance in other tumor types including breast cancer and B-lymphoid malignancy; and 2) somatic mutation of the MEN1 gene, first identified as the source of pathogenic germline mutations in patients with familial endocrinopathies, is found in a substantial fraction of non-familial parathyroid adenomas.

  20. COL11A1 in FAP polyps and in sporadic colorectal tumors

    International Nuclear Information System (INIS)

    Fischer, Heléne; Salahshor, Sima; Stenling, Roger; Björk, Jan; Lindmark, Gudrun; Iselius, Lennart; Rubio, Carlos; Lindblom, Annika

    2001-01-01

    We previously reported that the α-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of β-catenin. We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/β-catenin pathway. In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/β-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/β-catenin pathway in FAP and sporadic colorectal cancer

  1. Sporadic wind wave horse-shoe patterns

    Directory of Open Access Journals (Sweden)

    S. Yu. Annenkov

    1999-01-01

    Full Text Available The work considers three-dimensional crescent-shaped patterns often seen on water surface in natural basins and observed in wave tank experiments. The most common of these 'horse-shoe-like' patterns appear to be sporadic, i.e., emerging and disappearing spontaneously even under steady wind conditions. The paper suggests a qualitative model of these structures aimed at explaining their sporadic nature, physical mechanisms of their selection and their specific asymmetric form. First, the phenomenon of sporadic horse-shoe patterns is studied numerically using the novel algorithm of water waves simulation recently developed by the authors (Annenkov and Shrira, 1999. The simulations show that a steep gravity wave embedded into widespectrum primordial noise and subjected to small nonconservative effects typically follows the simple evolution scenario: most of the time the system can be considered as consisting of a basic wave and a single pair of oblique satellites, although the choice of this pair tends to be different at different instants. Despite the effective low-dimensionality of the multimodal system dynamics at relatively sho ' rt time spans, the role of small satellites is important: in particular, they enlarge the maxima of the developed satellites. The presence of Benjamin-Feir satellites appears to be of no qualitative importance at the timescales under consideration. The selection mechanism has been linked to the quartic resonant interactions among the oblique satellites lying in the domain of five-wave (McLean's class II instability of the basic wave: the satellites tend to push each other out of the resonance zone due to the frequency shifts caused by the quartic interactions. Since the instability domain is narrow (of order of cube of the basic wave steepness, eventually in a generic situation only a single pair survives and attains considerable amplitude. The specific front asymmetry is found to result from the interplay of quartic

  2. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

  3. Estimating the temporal and spatial risk of bluetongue related to the incursion of infected vectors into Switzerland

    Directory of Open Access Journals (Sweden)

    Griot C

    2008-10-01

    Full Text Available Abstract Background The design of veterinary and public health surveillance systems has been improved by the ability to combine Geographical Information Systems (GIS, mathematical models and up to date epidemiological knowledge. In Switzerland, an early warning system was developed for detecting the incursion of the bluetongue disease virus (BT and to monitor the frequency of its vectors. Based on data generated by this surveillance system, GIS and transmission models were used in order to determine suitable seasonal vector habitat locations and risk periods for a larger and more targeted surveillance program. Results Combined thematic maps of temperature, humidity and altitude were created to visualize the association with Culicoides vector habitat locations. Additional monthly maps of estimated basic reproduction number transmission rates (R0 were created in order to highlight areas of Switzerland prone to higher BT outbreaks in relation to both vector activity and transmission levels. The maps revealed several foci of higher risk areas, especially in northern parts of Switzerland, suitable for both vector presence and vector activity for 2006. Results showed a variation of R0 values comparing 2005 and 2006 yet suggested that Switzerland was at risk of an outbreak of BT, especially if the incursion arrived in a suitable vector activity period. Since the time of conducting these analyses, this suitability has proved to be the case with the recent outbreaks of BT in northern Switzerland. Conclusion Our results stress the importance of environmental factors and their effect on the dynamics of a vector-borne disease. In this case, results of this model were used as input parameters for creating a national targeted surveillance program tailored to both the spatial and the temporal aspect of the disease and its vectors. In this manner, financial and logistic resources can be used in an optimal way through seasonally and geographically adjusted

  4. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease

    NARCIS (Netherlands)

    I. Zerr; K. Kallenberg; D.M. Summers; C. Romero; A. Taratuto; U. Heinemann; M. Breithaupt; D. Varges; B. Meissner; A. Ladogana (Anna); M. Schuur (Maaike); S. Haik; S.J. Collins (Steven); G.H. Jansen (Gerard); G.B. Stokin; J. Pimentel; E. Hewer; D. Collie; P. Smith; H. Roberts; J.P. Brandel; P. Tikka-Kleemola (Päivi); M. Pocchiari (Maurizio); C. Begue; P. Cras (Patrick); R.G. Will; P. Sanchez-Juan (Pascual)

    2009-01-01

    textabstractSeveral molecular subtypes of sporadic Creutzfeldt-Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications

  5. Imaging movement-related activity in medicated Parkin-associated and sporadic Parkinson's disease

    DEFF Research Database (Denmark)

    van Eimeren, Thilo; Binkofski, Ferdinand; Buhmann, Carsten

    2010-01-01

    Treatment-related motor complications such as dyskinesias are a major problem in the long-term management of Parkinson's disease (PD). In sporadic PD, a relatively early onset of the disease is known to be associated with an early development of dyskinesias. Although linked with early onset...... selected movements. Patients with Parkin-associated and sporadic PD showed no difference in movement-related activation patterns. Moreover, the covariates 'age' and 'disease duration' similarly influenced brain activation in both patient groups. The present finding suggests that a stable long-term motor...

  6. Application of quantitative DTI metrics in sporadic CJD

    Directory of Open Access Journals (Sweden)

    E. Caverzasi

    2014-01-01

    Full Text Available Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob–Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1 to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM in sporadic Jakob–Creutzfeldt disease, 2 to study changes in mean diffusivity and atrophy over time and 3 to explore their relationship with clinical scales. Twenty-six sporadic Jakob–Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume, T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei, but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score and increasing mean diffusivity.

  7. Transmission of sporadic Creutzfeldt-Jakob disease by blood transfusion: risk factor or possible biases.

    Science.gov (United States)

    Puopolo, Maria; Ladogana, Anna; Vetrugno, Vito; Pocchiari, Maurizio

    2011-07-01

    The occurrence of transfusion transmissions of variant Creutzfeldt-Jakob disease (CJD) cases has reawakened attention to the possible similar risk posed by other forms of CJD. CJD with a definite or probable diagnosis (sporadic CJD, n = 741; genetic CJD, n = 175) and no-CJD patients with definite alternative diagnosis (n = 482) with available blood transfusion history were included in the study. The risk of exposure to blood transfusion occurring more than 10 years before disease onset and for some possible confounding factors was evaluated by calculating crude odds ratios (ORs). Variables with significant ORs in univariate analyses were included in multivariate logistic regression analyses. In the univariate model, blood transfusion occurring more than 10 years before clinical onset is 4.1-fold more frequent in sporadic CJD than in other neurologic disorders. This significance is lost when the 10-year lag time was not considered. Multivariate analyses show that the risk of developing sporadic CJD after transfusion increases (OR, 5.05) after adjusting for possible confounding factors. Analysis conducted on patients with genetic CJD did not reveal any significant risk factor associated with transfusion. This is the first case-control study showing a significant risk of transfusion occurring more than 10 years before clinical onset in sporadic CJD patients. It remains questionable whether the significance of these data is biologically plausible or the consequence of biases in the design of the study, but they counterbalance previous epidemiologic negative reports that might have overestimated the assessment of blood safety in sporadic CJD. © 2010 American Association of Blood Banks.

  8. Near Earth space sporadic radio emission busts occurring during sunrise

    Science.gov (United States)

    Dudnik, A. V.; Zaljubovsky, I. I.; Kartashev, V. M.; Lasarev, A. V.; Shmatko, E. S.

    1985-01-01

    During the period of low solar activity at sunrise the effect of sporadic high frequency near Earth space radio emission was experimentally discovered at middle latitudes. The possible mechanism of its origin is discussed.

  9. Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer

    DEFF Research Database (Denmark)

    Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei

    2017-01-01

    BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas...... was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p expression in polyps (p ..., no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages...

  10. Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer's disease

    International Nuclear Information System (INIS)

    Lannfelt, L.; Lilius, L.; Viitanen, M.; Winblad, B.; Basun, H.; Houlden, H.; Rossor, M.; Hardy, J.

    1995-01-01

    Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer's disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid presursor protein gene involvement in Alzheimer's disease families, as it is closely linked to the gene. Most cases of Alzheimer's disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer's disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. (au) (26 refs.)

  11. Evaluating Late Cretaceous OAEs and the influence of marine incursions on organic carbon burial in an expansive East Asian paleo-lake

    Science.gov (United States)

    Jones, Matthew M.; Ibarra, Daniel E.; Gao, Yuan; Sageman, Bradley B.; Selby, David; Chamberlain, C. Page; Graham, Stephan A.

    2018-02-01

    Expansive Late Cretaceous lacustrine deposits of East Asia offer unique stratigraphic records to better understand regional responses to global climate events, such as oceanic anoxic events (OAEs), and terrestrial organic carbon burial dynamics. This study presents bulk organic carbon isotopes (δ13Corg), elemental concentrations (XRF), and initial osmium ratios (187Os/188Os, Osi) from the Turonian-Coniacian Qingshankou Formation, a ∼5 Ma lacustrine mudstone succession in the Songliao Basin of northeast China. A notable δ13Corg excursion (∼ + 2.5‰) in organic carbon-lean Qingshankou Members 2-3 correlates to OAE3 in the Western Interior Basin (WIB) of North America within temporal uncertainty of high-precision age models. Decreases in carbon isotopic fractionation (Δ13C) through OAE3 in the WIB and Songliao Basin, suggest that significantly elevated global rates of organic carbon burial drew down pCO2, likely cooling climate. Despite this, Osi chemostratigraphy demonstrates no major changes in global volcanism or weathering trends through OAE3. Identification of OAE3 in a lake system is consistent with lacustrine records of other OAEs (e.g., Toarcian OAE), and underscores that terrestrial environments were sensitive to climate perturbations associated with OAEs. Additionally, the relatively radiogenic Osi chemostratigraphy and XRF data confirm that the Qingshankou Formation was deposited in a non-marine setting. Organic carbon-rich intervals preserve no compelling Osi evidence for marine incursions, an existing hypothesis for generating Member 1's prolific petroleum source rocks. Based on our results, we present a model for water column stratification and source rock deposition independent of marine incursions, detailing dominant biogeochemical cycles and lacustrine organic carbon burial mechanisms.

  12. The localization of facial motor impairment in sporadic Möbius syndrome.

    Science.gov (United States)

    Cattaneo, L; Chierici, E; Bianchi, B; Sesenna, E; Pavesi, G

    2006-06-27

    To investigate the neurophysiologic aspects of facial motor control in patients with sporadic Möbius syndrome defined as nonprogressive congenital facial and abducens palsy. The authors assessed 24 patients with sporadic Möbius syndrome by performing a complete clinical examination and neurophysiologic tests including facial nerve conduction studies, needle electromyography examination of facial muscles, and recording of the blink reflex and of the trigeminofacial inhibitory reflex. Two distinct groups of patients were identified according to neurophysiologic testing. The first group was characterized by increased facial distal motor latencies (DMLs) and poor recruitment of small and polyphasic motor unit action potentials (MUAPs). The second group was characterized by normal facial DMLs and neuropathic MUAPs. It is hypothesized that in the first group, the disorder is due to a rhombencephalic maldevelopment with selective sparing of small-size MUs, and in the second group, the disorder is related to an acquired nervous injury during intrauterine life, with subsequent neurogenic remodeling of MUs. The trigeminofacial reflexes showed that in most subjects of both groups, the functional impairment of facial movements was caused by a nuclear or peripheral site of lesion, with little evidence of brainstem interneuronal involvement. Two different neurophysiologically defined phenotypes can be distinguished in sporadic Möbius syndrome, with different pathogenetic implications.

  13. Reactive GTS Allocation Protocol for Sporadic Events Using the IEEE 802.15.4

    Directory of Open Access Journals (Sweden)

    Mukhtar Azeem

    2014-01-01

    by the IEEE 802.15.4 standard. The proposed control protocol ensures that a given offline sporadic schedule can be adapted online in a timely manner such that the static periodic schedule has not been disturbed and the IEEE 802.15.4 standard compliance remains intact. The proposed protocol is simulated in OPNET. The simulation results are analyzed and presented in this paper to prove the correctness of the proposed protocol regarding the efficient real-time sporadic event delivery along with the periodic event propagation.

  14. Association between rs6812193 polymorphism and sporadic Parkinson's disease susceptibility.

    Science.gov (United States)

    Huo, Qiang; Li, Tao; Zhao, Peiqing; Wang, Lianqing

    2015-08-01

    Recently, the association of a single nucleotide polymorphism rs6812193 C/T with sporadic Parkinson's disease (PD) susceptibility has been widely evaluated, but the results remained inconsistent. This association should be clarified because of the importance of it on human health and quality of life. We performed a comprehensive meta-analysis to evaluate the association between the rs6812193 polymorphism and sporadic PD. PubMed was used to retrieve articles published up to June 2014 for all studies evaluating the rs6812193 polymorphism and PD in humans. Ethnicity-specific subgroup analysis was also performed based on ethnicity susceptibility. A total of 17 independent study samples (15 Caucasians and 2 Asians) including 17,956 cases and 52,751 controls were used in the presented study. The MAFT (minor allele T frequency) in PD patients of European descent is obviously higher than Asian cases (p susceptibility among overall samples (OR 0.882, 95 % CI 0.856-0.908) and Caucasian population (OR 0.881, 95 % CI 0.856-0.907), but not in Asian samples (OR 0.918, 95 % CI 0.721-1.168). No evidence of publication bias was observed. Throughout our analysis, the rs6812193 polymorphism is significantly associated with sporadic PD susceptibility in Caucasian samples, and ethnicity might be the key point of inconsistency in rs6812193 studies. Further studies are warranted to re-examine the observed associations, especially in different ethnicities.

  15. Higher cytoplasmic and nuclear poly(ADP-ribose) polymerase expression in familial than in sporadic breast cancer

    NARCIS (Netherlands)

    Klauke, M.L.; Hoogerbrugge-van der Linden, N.; Budczies, J.; Bult, P.; Prinzler, J.; Radke, C.; van Krieken, J.H.; Dietel, M.; Denkert, C.; Muller, B.M.

    2012-01-01

    Poly(ADP-ribose) polymerase 1 (PARP) is a key element of the single-base excision pathway for repair of DNA single-strand breaks. To compare the cytoplasmic and nuclear poly(ADP-ribose) expression between familial (BRCA1, BRCA2, or non BRCA1/2) and sporadic breast cancer, we investigated 39 sporadic

  16. Multiple imputation by chained equations for systematically and sporadically missing multilevel data.

    Science.gov (United States)

    Resche-Rigon, Matthieu; White, Ian R

    2018-06-01

    In multilevel settings such as individual participant data meta-analysis, a variable is 'systematically missing' if it is wholly missing in some clusters and 'sporadically missing' if it is partly missing in some clusters. Previously proposed methods to impute incomplete multilevel data handle either systematically or sporadically missing data, but frequently both patterns are observed. We describe a new multiple imputation by chained equations (MICE) algorithm for multilevel data with arbitrary patterns of systematically and sporadically missing variables. The algorithm is described for multilevel normal data but can easily be extended for other variable types. We first propose two methods for imputing a single incomplete variable: an extension of an existing method and a new two-stage method which conveniently allows for heteroscedastic data. We then discuss the difficulties of imputing missing values in several variables in multilevel data using MICE, and show that even the simplest joint multilevel model implies conditional models which involve cluster means and heteroscedasticity. However, a simulation study finds that the proposed methods can be successfully combined in a multilevel MICE procedure, even when cluster means are not included in the imputation models.

  17. The lunar tide in sporadic E

    Directory of Open Access Journals (Sweden)

    R. J. Stening

    1999-10-01

    Full Text Available It seems that the wind shear theory is accepted for the explanation of sporadic E at mid and low latitudes. Some examples from Arecibo are displayed to show this. The effect of lunar tides should then modify the wind-shear theory in a manner that yields the observed features of the lunar tide in the critical frequency foEs and the height h'Es of the sporadic E. This is shown to imply that the phase of the lunar tide in h'Es should be the same as the phase of the lunar tide in the eastward wind and that the phase of the lunar tide in foEs is three hours later. Hourly values of foEs, f bEs (the blanketing critical frequency and h'Es from several observatories are analysed for the lunar semidiurnal tide. It is found that the phase of the tide in foEs is often about 3 hours later than for h'Es in agreement with the theory. Seasonal variations in the tide are also examined with the statistically most significant results (largest amplitudes usually occurring in summer. After reviewing the many difficulties associated with determining the lunar tide in Es, both experimentally and theoretically, the analysed phase results are compared with what might be expected from Hagan's global scale wave model. Agreement is only fair (a success rate of 69% among the cases examined but probably as good as might be expected.Key words. Ionosphere (ionosphere – atmosphere interactions – ionospheric irregularities, Meteorology and atmosphere dynamics (waves and tides

  18. High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece.

    Science.gov (United States)

    Sarika, H L; Papathoma, A; Garofalaki, M; Vasileiou, V; Vlassopoulou, B; Anastasiou, E; Alevizaki, M

    2012-12-01

    Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. In our study, we found that 7·75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece. © 2012 Blackwell Publishing Ltd.

  19. [The practice guideline 'Dermatomyositis, polymyositis and sporadic inclusion body myositis'

    NARCIS (Netherlands)

    Hoogendijk, J.E.; Bijlsma, J.W.J.; Engelen, B.G.M. van; Lindeman, E.J.M.; Royen-Kerkhof, A. van; Rie, M.A. de; Visser, M. de; Jennekens, F.G.I.

    2005-01-01

    This guideline presents recommendations for the diagnosis and treatment of dermatomyositis, polymyositis and sporadic inclusion body myositis (sIBM) according to the best available evidence. Characteristic skin abnormalities can be sufficient for the diagnosis of dermatomyositis. In case of doubt, a

  20. Hypermethylation of the FANCC and FANCL Promoter Regions in Sporadic Acute Leukaemia

    Directory of Open Access Journals (Sweden)

    C. J. Hess

    2008-01-01

    Full Text Available Objective: Inactivation of the FA-BRCA pathway results in chromosomal instability. Fanconi anaemia (FA patients have an inherited defect in this pathway and are strongly predisposed to the development of acute myeloid leukaemia (AML. Studies in sporadic cancers have shown promoter methylation of the FANCF gene in a significant proportion of various solid tumours. However, only a single leukaemic case with methylation of one of the FA-BRCA genes has been described to date, i.e. methylation of FANCF in cell line CHRF-288. We investigated the presence of aberrant methylation in 11 FA-BRCA genes in sporadic cases of leukaemia.

  1. Sporadic-E associated with the Leonid meteor shower event of November 1998 over low and equatorial latitudes

    Directory of Open Access Journals (Sweden)

    H. Chandra

    2001-01-01

    Full Text Available Rapid radio soundings were made over Ahmedabad, a low latitude station during the period 16–20 November 1998 to study the sporadic-E layer associated with the Leonid shower activity using the KEL Aerospace digital ionosonde. Hourly ionograms for the period 11 November to 24 November were also examined during the years from 1994 to 1998. A distinct increase in sporadic-E layer occurrence is noticed on 17, 18 and 19 November from 1996 to 1998. The diurnal variations  of  f0Es and fbEs also show significantly enhanced values for the morning hours of 18 and 19 November 1998. The ionograms clearly show strong sporadic-E reflections at times of peak shower activity with multiple traces in the altitude range of 100–140 km in few ionograms. Sporadic-E layers with multiple structures in altitude are also seen in some of the ionograms (quarter hourly at Thumba, situated near the magnetic equator. Few of ionograms recorded at Kodaikanal, another equatorial station, also show sporadic- E reflections in spite of the transmitter power being significantly lower. These new results highlighting the effect of intense meteor showers in the equatorial and low latitude E-region are presented.Key words. Ionosphere (equatorial ionosphere – Radio science (ionospheric physics

  2. When does ALS start? ADAR2-GluA2 hypothesis for the etiology of sporadic ALS

    Directory of Open Access Journals (Sweden)

    Takuto eHideyama

    2011-11-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most common adult-onset motor neuron disease. More than 90% of ALS cases are sporadic, and the majority of sporadic ALS patients do not carry mutations in genes causative of familial ALS; therefore, investigation specifically targeting sporadic ALS is needed to discover the pathogenesis. The motor neurons of sporadic ALS patients express unedited GluA2 mRNA at the Q/R site in a disease-specific and motor neuron-selective manner. GluA2 is a subunit of the AMPA receptor, and it has a regulatory role in the Ca2+-permeability of the AMPA receptor after the genomic Q codon is replaced with the R codon in mRNA by adenosine-inosine conversion, which is mediated by adenosine deaminase acting on RNA 2 (ADAR2. Therefore, ADAR2 activity may not be sufficient to edit all GluA2 mRNA expressed in the motor neurons of ALS patients. To investigate whether deficient ADAR2 activity plays pathogenic roles in sporadic ALS, we generated genetically modified mice (AR2 in which the ADAR2 gene was conditionally knocked out in the motor neurons. AR2 mice showed an ALS-like phenotype with the death of ADAR2-lacking motor neurons. Notably, the motor neurons deficient in ADAR2 survived when they expressed only edited GluA2 in AR2/GluR-BR/R (AR2res mice, in which the endogenous GluA2 alleles were replaced by the GluR-BR allele that encoded edited GluA2. In heterozygous AR2 mice with only one ADAR2 allele, approximately 20% of the spinal motor neurons expressed unedited GluA2 and underwent degeneration, indicating that half-normal ADAR2 activity is not sufficient to edit all GluA2 expressed in motor neurons. It is likely therefore that the expression of unedited GluA2 causes the death of motor neurons in sporadic ALS. We hypothesize that a progressive downregulation of ADAR2 activity plays a critical role in the pathogenesis of sporadic ALS and that the pathological process commences when motor neurons express unedited GluA2.

  3. Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease

    Science.gov (United States)

    Gargini, Ricardo; García, Esther; Perry, George

    2017-01-01

    Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer's pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer's patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer's disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients' fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer's fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging. PMID:29201274

  4. Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lannfelt, L; Lilius, L; Viitanen, M; Winblad, B; Basun, H [Huddinge Hospital, Karolinska Institute, Dept. of Geriatric Medicine, (Sweden); Houlden, H; Rossor, M [St. Mary` s Hospital, Dept. of Neurology, Medical School, London (United Kingdom); Hardy, J [University of South Florida, Suncoast Alzheimer` s Disease Research Labs, Department of Psychiatry, Tampa (United States)

    1995-02-01

    Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer`s disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid presursor protein gene involvement in Alzheimer`s disease families, as it is closely linked to the gene. Most cases of Alzheimer`s disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer`s disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. (au) (26 refs.).

  5. Molecular profile and copy number analysis of sporadic colorectal cancer in Taiwan

    Directory of Open Access Journals (Sweden)

    Li Ling-Hui

    2011-06-01

    Full Text Available Abstract Background Colorectal cancer (CRC is a major health concern worldwide, and recently becomes the most common cancer in Asia. The case collection of this study is one of the largest sets of CRC in Asia, and serves as representative data for investigating genomic differences between ethnic populations. We took comprehensive and high-resolution approaches to compare the clinicopathologic and genomic profiles of microsatellite instability (MSI vs. microsatellite stability (MSS in Taiwanese sporadic CRCs. Methods 1,173 CRC tumors were collected from the Taiwan population, and sequencing-based microsatellite typing assay was used to determine MSI and MSS. Genome-wide SNP array was used to detect CN alterations in 16 MSI-H and 13 MSS CRCs and CN variations in 424 general controls. Gene expression array was used to evaluate the effects of CN alterations, and quantitative PCR methods were used to replicate the findings in independent clinical samples. Results These 1,173 CRC tumors can be classified into 75 high-frequency MSI (MSI-H (6.4%, 96 low-frequency MSI (8.2% and 1,002 MSS (85.4%. Of the 75 MSI-H tumors, 22 had a BRAF mutation and 51 showed MLH1 promoter hypermethylation. There were distinctive differences in the extent of CN alterations between CRC MSS and MSI-H subtypes (300 Mb vs. 42 Mb per genome, p-value Conclusions Sporadic CRCs with MSI-H displayed distinguishable clinicopathologic features, which differ from those of MSS. Genomic profiling of the two types of sporadic CRCs revealed significant differences in the extent and distribution of CN alterations in the cancer genome. More than half of expressed genes showing CN differences can directly contribute to their expressional diversities, and the biological functions of the genes associated with CN changes in sporadic CRCs warrant further investigation to establish their possible clinical implications.

  6. A genome-wide investigation of copy number variation in patients with sporadic brain arteriovenous malformation.

    Directory of Open Access Journals (Sweden)

    Nasrine Bendjilali

    Full Text Available Brain arteriovenous malformations (BAVM are clusters of abnormal blood vessels, with shunting of blood from the arterial to venous circulation and a high risk of rupture and intracranial hemorrhage. Most BAVMs are sporadic, but also occur in patients with Hereditary Hemorrhagic Telangiectasia, a Mendelian disorder caused by mutations in genes in the transforming growth factor beta (TGFβ signaling pathway.To investigate whether copy number variations (CNVs contribute to risk of sporadic BAVM, we performed a genome-wide association study in 371 sporadic BAVM cases and 563 healthy controls, all Caucasian. Cases and controls were genotyped using the Affymetrix 6.0 array. CNVs were called using the PennCNV and Birdsuite algorithms and analyzed via segment-based and gene-based approaches. Common and rare CNVs were evaluated for association with BAVM.A CNV region on 1p36.13, containing the neuroblastoma breakpoint family, member 1 gene (NBPF1, was significantly enriched with duplications in BAVM cases compared to controls (P = 2.2×10(-9; NBPF1 was also significantly associated with BAVM in gene-based analysis using both PennCNV and Birdsuite. We experimentally validated the 1p36.13 duplication; however, the association did not replicate in an independent cohort of 184 sporadic BAVM cases and 182 controls (OR = 0.81, P = 0.8. Rare CNV analysis did not identify genes significantly associated with BAVM.We did not identify common CNVs associated with sporadic BAVM that replicated in an independent cohort. Replication in larger cohorts is required to elucidate the possible role of common or rare CNVs in BAVM pathogenesis.

  7. Cortical restricted diffusion as the predominant MRI finding in sporadic Creutzfeldt-Jakob disease

    Energy Technology Data Exchange (ETDEWEB)

    Talbott, Sabrina D.; Sattenberg, Ronald J.; Heidenreich, Jens O. (Dept. of Radiology, Univ. of Louisville, Louisville (United States)), e-mail: sdtalb02@gwise.louisville.edu; Plato, Brian M (Dept. of Neurology, Univ. of Louisville, Louisville (United States)); Parker, John (Dept. of Pathology and Laboratory Medicine, Univ. of Louisville, Louisville (United States))

    2011-04-15

    Creutzfeldt-Jakob disease is a rare and fatal neurodegenerative disorder with MR findings predominantly limited to the grey matter of the cortex and the basal ganglia. Sporadic Creutzfeldt-Jakob disease can produce a spectrum of MR imaging findings of the brain, most notably on DWI and FLAIR sequences. Involvement of the basal ganglia and neocortex is the most common finding, but isolated involvement of the cortex can also be seen. We describe the clinical history and MRI findings of three patients with sporadic Creutzfeldt-Jakob disease confirmed by brain biopsy or autopsy and review the literature of imaging manifestations of this disease

  8. Cortical restricted diffusion as the predominant MRI finding in sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Talbott, Sabrina D.; Sattenberg, Ronald J.; Heidenreich, Jens O.; Plato, Brian M; Parker, John

    2011-01-01

    Creutzfeldt-Jakob disease is a rare and fatal neurodegenerative disorder with MR findings predominantly limited to the grey matter of the cortex and the basal ganglia. Sporadic Creutzfeldt-Jakob disease can produce a spectrum of MR imaging findings of the brain, most notably on DWI and FLAIR sequences. Involvement of the basal ganglia and neocortex is the most common finding, but isolated involvement of the cortex can also be seen. We describe the clinical history and MRI findings of three patients with sporadic Creutzfeldt-Jakob disease confirmed by brain biopsy or autopsy and review the literature of imaging manifestations of this disease

  9. Case-Control Studies of Sporadic Enteric Infections: A Review and Discussion of Studies Conducted Internationally from 1990 to 2009

    Science.gov (United States)

    Fullerton, Kathleen E.; Scallan, Elaine; Kirk, Martyn D.; Mahon, Barbara E.; Angulo, Frederick J.; de Valk, Henriette; van Pelt, Wilfrid; Gauci, Charmaine; Hauri, Anja M.; Majowicz, Shannon; O’Brien, Sarah J.

    2015-01-01

    Epidemiologists have used case-control studies to investigate enteric disease outbreaks for many decades. Increasingly, case-control studies are also used to investigate risk factors for sporadic (not outbreak-associated) disease. While the same basic approach is used, there are important differences between outbreak and sporadic disease settings that need to be considered in the design and implementation of the case-control study for sporadic disease. Through the International Collaboration on Enteric Disease “Burden of Illness” Studies (the International Collaboration), we reviewed 79 case-control studies of sporadic enteric infections caused by nine pathogens that were conducted in 22 countries and published from 1990 through to 2009. We highlight important methodological and study design issues (including case definition, control selection, and exposure assessment) and discuss how approaches to the study of sporadic enteric disease have changed over the last 20 years (e.g., making use of more sensitive case definitions, databases of controls, and computer-assisted interviewing). As our understanding of sporadic enteric infections grows, methods and topics for case-control studies are expected to continue to evolve; for example, advances in understanding of the role of immunity can be used to improve control selection, the apparent protective effects of certain foods can be further explored, and case-control studies can be used to provide population-based measures of the burden of disease. PMID:22443481

  10. Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES).

    Science.gov (United States)

    Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong; Wang, Wenju; Jiang, Lihong

    2018-03-05

    BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (PASD (PASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.

  11. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  12. Measuring sporadic gastrointestinal illness associated with drinking water - an overview of methodologies.

    Science.gov (United States)

    Bylund, John; Toljander, Jonas; Lysén, Maria; Rasti, Niloofar; Engqvist, Jannes; Simonsson, Magnus

    2017-06-01

    There is an increasing awareness that drinking water contributes to sporadic gastrointestinal illness (GI) in high income countries of the northern hemisphere. A literature search was conducted in order to review: (1) methods used for investigating the effects of public drinking water on GI; (2) evidence of possible dose-response relationship between sporadic GI and drinking water consumption; and (3) association between sporadic GI and factors affecting drinking water quality. Seventy-four articles were selected, key findings and information gaps were identified. In-home intervention studies have only been conducted in areas using surface water sources and intervention studies in communities supplied by ground water are therefore needed. Community-wide intervention studies may constitute a cost-effective alternative to in-home intervention studies. Proxy data that correlate with GI in the community can be used for detecting changes in the incidence of GI. Proxy data can, however, not be used for measuring the prevalence of illness. Local conditions affecting water safety may vary greatly, making direct comparisons between studies difficult unless sufficient knowledge about these conditions is acquired. Drinking water in high-income countries contributes to endemic levels of GI and there are public health benefits for further improvements of drinking water safety.

  13. SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

    Directory of Open Access Journals (Sweden)

    Christine S. Higham

    2017-01-01

    Full Text Available Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1- associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST has been reported. Methods. We evaluated the objective response (OR rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%. Results. 34 NF1 (median age 33 years and 14 sporadic (median age 40 years MPNST patients enrolled. Five of 28 (17.9% evaluable NF1 MPNST patients had a partial response (PR, as did 4 of 9 (44.4% patients with sporadic MPNST. Stable disease (SD was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

  14. MRI of sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Kong, A.; Vliet, A. Van der.

    2008-01-01

    Full text: The key MRI findings in five cases of sporadic Creutzfeldt-Jakob disease (CJD) are illustrated with four 'definite' and one 'probable' according to World Health Organization criteria. Close attention to fluid-attenuation inversion recovery and diffusion-weighted imaging sequences are important for diagnosis, noting especially restricted diffusion in cortical and deep grey matter. Our study and those of others show predominant cortical, caudate and thalamic involvement. This pattern is highly sensitive and specific for the diagnosis. Fluid-attenuation inversion recovery and diffusion-weighted imaging signal abnormality becomes progressively more extensive and bilateral as disease progresses, but may become less pronounced in end-stage disease because of atrophy.

  15. Sporadic Endolymphatic Sac Tumor-A Very Rare Cause of Hearing Loss, Tinnitus, and Dizziness

    DEFF Research Database (Denmark)

    Schnack, Didde Trærup; Kiss, Katalin; Hansen, Søren

    2017-01-01

    Sporadic endolymphatic sac tumor is a very rare neoplasm. It is low malignant, locally destructive and expansive, but non-metastasizing. The tumor is very rare in the sporadic form, but more often associated with Von Hippel-Lindau disease. A 65-year old man with left sided tinnitus and hearing loss......-operative freeze-microscopy showed inflammation tissue, whereas subsequent microscopy showed papillary-cystic endolymphatic sac tumor. Endolymphatic sac tumor is a rare neoplasm. The tumor may present with asymmetrically sensory neural hearing loss with or without tinnitus, dizziness and facial nerve paresis...

  16. Allele doses of apolipoprotein E type {epsilon}4 in sporadic late-onset Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; Aouizerate, A.; Gerard, N. [Regional Center of Neurogenetics, Paris (France)] [and others

    1995-12-18

    Apoliprotein E, type {epsilon}4 allele (ApoE-{epsilon}4) is associated with late-onset sporadic Alzheimer`s disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-{epsilon}4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging. 26 refs., 2 figs., 1 tab.

  17. Physical function and muscle strength in sporadic inclusion body myositis

    DEFF Research Database (Denmark)

    Jørgensen, Anders N; Aagaard, Per; Nielsen, Jakob L

    2017-01-01

    INTRODUCTION: In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. METHODS: The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30-s...

  18. Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test.

    LENUS (Irish Health Repository)

    Kimmich, Okka

    2012-02-01

    Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are much more prevalent than familial. The temporal discrimination threshold is the shortest time interval at which two stimuli are detected to be asynchronous and has been shown to be abnormal in adult-onset primary torsion dystonia. The aim was to determine the frequency of abnormal temporal discrimination thresholds in patients with sporadic adult-onset primary torsion dystonia and their first-degree relatives. We hypothesized that abnormal temporal discrimination thresholds in first relatives would be compatible with an autosomal dominant endophenotype. Temporal discrimination thresholds were examined in 61 control subjects (39 subjects <50 years of age; 22 subjects >50 years of age), 32 patients with sporadic adult-onset primary torsion dystonia (cervical dystonia n = 30, spasmodic dysphonia n = 1 and Meige\\'s syndrome n = 1) and 73 unaffected first-degree relatives (36 siblings, 36 offspring and one parent) using visual and tactile stimuli. Z-scores were calculated for all subjects; a Z > 2.5 was considered abnormal. Abnormal temporal discrimination thresholds were found in 1\\/61 (2%) control subjects, 27\\/32 (84%) patients with adult-onset primary torsion dystonia and 32\\/73 (44%) unaffected relatives [siblings (20\\/36; 56%), offspring (11\\/36; 31%) and one parent]. When two or more relatives were tested in any one family, 22 of 24 families had at least one first-degree relative with an abnormal temporal discrimination threshold. The frequency of abnormal temporal discrimination thresholds in first-degree relatives of patients with sporadic adult-onset primary torsion dystonia is compatible with an autosomal dominant disorder and supports the hypothesis that apparently sporadic adult-onset primary torsion dystonia is genetic in origin.

  19. Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test.

    Science.gov (United States)

    Kimmich, Okka; Bradley, David; Whelan, Robert; Mulrooney, Nicola; Reilly, Richard B; Hutchinson, Siobhan; O'Riordan, Sean; Hutchinson, Michael

    2011-09-01

    Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are much more prevalent than familial. The temporal discrimination threshold is the shortest time interval at which two stimuli are detected to be asynchronous and has been shown to be abnormal in adult-onset primary torsion dystonia. The aim was to determine the frequency of abnormal temporal discrimination thresholds in patients with sporadic adult-onset primary torsion dystonia and their first-degree relatives. We hypothesized that abnormal temporal discrimination thresholds in first relatives would be compatible with an autosomal dominant endophenotype. Temporal discrimination thresholds were examined in 61 control subjects (39 subjects 50 years of age), 32 patients with sporadic adult-onset primary torsion dystonia (cervical dystonia n = 30, spasmodic dysphonia n = 1 and Meige's syndrome n = 1) and 73 unaffected first-degree relatives (36 siblings, 36 offspring and one parent) using visual and tactile stimuli. Z-scores were calculated for all subjects; a Z > 2.5 was considered abnormal. Abnormal temporal discrimination thresholds were found in 1/61 (2%) control subjects, 27/32 (84%) patients with adult-onset primary torsion dystonia and 32/73 (44%) unaffected relatives [siblings (20/36; 56%), offspring (11/36; 31%) and one parent]. When two or more relatives were tested in any one family, 22 of 24 families had at least one first-degree relative with an abnormal temporal discrimination threshold. The frequency of abnormal temporal discrimination thresholds in first-degree relatives of patients with sporadic adult-onset primary torsion dystonia is compatible with an autosomal dominant disorder and supports the hypothesis that apparently sporadic adult-onset primary torsion dystonia is genetic in origin.

  20. CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients.

    Science.gov (United States)

    Debouki-Joudi, Saoussen; Trifa, Fatma; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

    2017-01-01

    Tumour suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer initiation. The aim of this study was to assess the extent of methylation of APC gene promoter in 91 sporadic and 44 familial cases of Tunisian patients with breast cancer (BC) in. The frequency of APC promoter methylation is somewhat similar for sporadic and familial breast cancer cases, (52.1%, and 54.5% respectively). For sporadic breast cancer patients, there was a significant correlation of APC promoter hypermethylation with TNM stage (p = 0.024) and 3-year survival (p = 0.025). Regarding the hormonal status (HR), we found significant association between negativity to PR and unmethylated APC (p= 0.005) while ER and Her2/neu are not correlated. Moreover, unmethylated APC promoter is more frequent in tumours expressing at least one out the 3 proteins compared to triple negative cases (p= 0.053). On the other hand, aberrant methylation of APC was associated with tumour size (p = 0.036), lymph node (p = 0.028), distant metastasis (p = 0.031), and 3-year survival (p = 0.046) in the group of patients with familial breast cancer. Moreover, patients with sporadic breast cancer displaying the unmethylated profile have a significant prolonged overall survival compared to those with the methylated pattern of APC promoter (p log rank = 0.008). Epigenetic change at the CpG islands in the APC promoter was associated with the silence of its transcript and the loss of protein expression suggesting that this event is the main mechanism regulating the APC expression in breast cancer. In conclusion, our data showed that the loss of APC through aberrant methylation is associated with the aggressive behavior of both sporadic and familial breast cancer in Tunisian patients.

  1. CT and MRI in iatrogenic and sporadic Creutzfeldt-Jakob disease: as far as imaging perseives

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Santos, J.M. [Servicio de Radiodiagnostico, HU Dr. Morales Meseguer, Murcia (Spain)]|[Section of Neuroradiology, HU Virgen de la Arrixaca, Murcia (Spain); Lopez Corbalan, J.A. [Section of Neuroradiology, HU Virgen de la Arrixaca, Murcia (Spain); Martinez-Lage, J.F. [Service of Neurosurgery, HU Virgen de la Arrixaca, Murcia (Spain); Sicilis Guillen, J. [Service of Neurology, HU Virgen de la Arrixaca, Murcia (Spain)

    1996-04-01

    Creutzfeldt-Jakob Disease (CJD), an invariably fatal dementing illness, affects patients in middle and old age (sporadic form). However, the association of CJD with certain treatments (iatrogenic form) has been described in younger patients. The clinical onset of the two forms seems to differ; in the iatrogenic form a high frequency of the ataxic CJD variant has been reported. Nowadays, a definitive diagnosis of CJD is exclusively histological. We present five cases of CJD, one sporadic and the others iatrogenic, following dura mater grafts and analyse their CT and MRI features. CT typically demonstrates brain atrophy, generally progressive, but in sporadic CJD midfield MRI also showed abnormal signal, with predominant deep grey matter involvement. The use of narrow windows with proton-density sequences may reveal subtle cortical signal abnormalities not clearly visible with conventional windows. The early demonstration of these changes, in the appropriate clinical context, may suggest CJD and this supports the use of mid- or high magnetic fields in the diagnosis of CJD and other forms of dementia. In our cases of iatrogenic CJD, low-field MRI did not reveal more than the progressive atrophy displayed by CT, and raises the question on the one hand of possible differences, based on imaging, from the sporadic form, and on the other of the lack of sensitivity of low-field magnets to signal changes in CJD. (orig.)

  2. CT and MRI in iatrogenic and sporadic Creutzfeldt-Jakob disease: as far as imaging perseives

    International Nuclear Information System (INIS)

    Garcia Santos, J.M.; Lopez Corbalan, J.A.; Martinez-Lage, J.F.; Sicilis Guillen, J.

    1996-01-01

    Creutzfeldt-Jakob Disease (CJD), an invariably fatal dementing illness, affects patients in middle and old age (sporadic form). However, the association of CJD with certain treatments (iatrogenic form) has been described in younger patients. The clinical onset of the two forms seems to differ; in the iatrogenic form a high frequency of the ataxic CJD variant has been reported. Nowadays, a definitive diagnosis of CJD is exclusively histological. We present five cases of CJD, one sporadic and the others iatrogenic, following dura mater grafts and analyse their CT and MRI features. CT typically demonstrates brain atrophy, generally progressive, but in sporadic CJD midfield MRI also showed abnormal signal, with predominant deep grey matter involvement. The use of narrow windows with proton-density sequences may reveal subtle cortical signal abnormalities not clearly visible with conventional windows. The early demonstration of these changes, in the appropriate clinical context, may suggest CJD and this supports the use of mid- or high magnetic fields in the diagnosis of CJD and other forms of dementia. In our cases of iatrogenic CJD, low-field MRI did not reveal more than the progressive atrophy displayed by CT, and raises the question on the one hand of possible differences, based on imaging, from the sporadic form, and on the other of the lack of sensitivity of low-field magnets to signal changes in CJD. (orig.)

  3. The P413L chromogranin B variation in French patients with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Blasco, Hélène; Corcia, Philippe; Veyrat-Durebex, Charlotte; Coutadeur, Cathleen; Fournier, Clémentine; Camu, William; Gordon, Paul; Praline, Julien; Andres, Christian R; Vourc'h, Patrick

    2011-05-01

    Chromogranins interact with mutant forms of superoxide dismutase 1 (SOD1) responsible for a portion of familial amyotrophic lateral sclerosis (ALS). A particular variation (P413L) in the chromogranin B gene, CHGB, has been recently associated with an earlier age at onset in both familial and sporadic ALS. The aim of our study was to evaluate the P413L chromogranin variation in French patients with sporadic amyotrophic lateral sclerosis. We developed a High Resolution DNA Melting (HRM) protocol to analyse the P413L variation in the CHGB gene in 540 French patients with sporadic ALS and 504 controls. The clinical characteristics of patients were analysed in relation to their genotype. Results showed that our study on a large cohort of French-Caucasian patients with SALS and controls failed to confirm an increased frequency of the 413L variant in SALS patients. This frequency was 5.3% in the SALS population and 5.5% in the control group. Moreover, we did not observe a previous observation of a difference of age at onset between T-allele carriers and non-carriers (median age of onset 60.4 vs. 62.0 years of age, respectively). Thus, our findings do not support the 413L variant of rs742710 as a risk factor for sporadic ALS in the French population.

  4. Sporadic-E associated with the Leonid meteor shower event of November 1998 over low and equatorial latitudes

    Directory of Open Access Journals (Sweden)

    H. Chandra

    Full Text Available Rapid radio soundings were made over Ahmedabad, a low latitude station during the period 16–20 November 1998 to study the sporadic-E layer associated with the Leonid shower activity using the KEL Aerospace digital ionosonde. Hourly ionograms for the period 11 November to 24 November were also examined during the years from 1994 to 1998. A distinct increase in sporadic-E layer occurrence is noticed on 17, 18 and 19 November from 1996 to 1998. The diurnal variations 
    of  f0Es and fbEs also show significantly enhanced values for the morning hours of 18 and 19 November 1998. The ionograms clearly show strong sporadic-E reflections at times of peak shower activity with multiple traces in the altitude range of 100–140 km in few ionograms. Sporadic-E layers with multiple structures in altitude are also seen in some of the ionograms (quarter hourly at Thumba, situated near the magnetic equator. Few of ionograms recorded at Kodaikanal, another equatorial station, also show sporadic- E reflections in spite of the transmitter power being significantly lower. These new results highlighting the effect of intense meteor showers in the equatorial and low latitude E-region are presented.

    Key words. Ionosphere (equatorial ionosphere – Radio science (ionospheric physics

  5. The survival of patients with Stage III Colon Cancer is improved in HNPCC compared with sporadic cases. A Danish registry based study

    DEFF Research Database (Denmark)

    Brixen, Line Merrild; Bernstein, Inge Thomsen; Bülow, Steffen

    2013-01-01

    AIM: Patients with hereditary non-polyposis colorectal cancer (HNPCC) seem to have a better prognosis than those with sporadic colon cancer (CC)s. The aim was to compare survival after stage III CC in patients with HNPCC with those having sporadic CC. METHOD: 230 patients with hereditary cancer...... from The Danish HNPCC-Register and 3557 patients with sporadic CC from The Danish Colorectal Cancer Database, diagnosed during May 2001-December 2008 were included. HNPCC patients were classified according to Mismatch Repair mutation status and family pedigree. Sporadic cases had no known family...... history of cancer. Patient characteristics, geographic differences and survival data were analyzed. RESULTS: The overall survival (OS) was better in HNPCC patients compared to sporadic CC after stratification for sex and age (p=0.02; CI 1.04-1.7). The 5-year survival was 70% in HNPCC patients compared...

  6. Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

    Science.gov (United States)

    Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei; Kuasne, Hellen; Spencer, Ranyell Matheus; Nakagawa, Wilson Toshihiko; Bezerra, Tiago Santoro; Kupper, Bruna Catin; Takahashi, Renata Maymi; Barros Filho, Mateus; Rogatto, Silvia Regina; Lopes, Ademar

    2017-11-13

    Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. This study aimed to investigate the expression levels of the ERβ1, ERβ2, ERβ4 and ERβ5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. Decreased expression of ERβ isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERβ1 and ERβ5 expression levels were associated with better disease-free survival (p = 0.002). These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

  7. Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    S Birla

    2016-01-01

    Full Text Available Background and Objectives: Primary hyperparathyroidism (PHPT can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1 is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.

  8. Earth's influx of different populations of sporadic meteoroids from photographic and television data

    International Nuclear Information System (INIS)

    Ceplecha, Z.

    1988-01-01

    Precise photographic and television double- and multi-station data on 3624 sporadic meteors in the mass range from 2 x 10 -5 grams to 2 x 10 7 grams form the basis of this paper. The applied classification criteria and procedures are defined and described. A survey of 7 different populations of sporadic meteoroids known so far is presented. The total numbers and masses of meteoroids as a function of mass are given for individual groups and for all sporadic meteors. The absolute calibration of the influx to the Earth was carried out by comparison with the results of Halliday et al. (1984). The comparison with the visual and cratering data revealed good agreement in the narrow ''visual'' interval of masses, and disagreement in the extrapolated parts of the visual and cratering flux curves. The slope of the cumulative number curve for the meteorite-dropping fireballs (type I) with masses larger than 1 kg was found as -0.69 in perfect agreement with the results of Halliday et al. (1984). The final mass scale derived in this paper is situated between the scale of McCrosky and the scale of Halliday. The relative significance of the different groups of meteoroids changes with the mass quite dramatically. The total influx of sporadic meteoroids in the mass interval of 12 orders from 2 x 10 7 to 2 x 10 -5 grams resulted in 5 x 10 9 grams per year for the entire Earth's surface. Most of this mass comes in the form of larger meteoroids. Bulk densities and ablation coefficient are presented for the individual meteor groups depending on different ablation models of several authors and some extreme concepts of this problem are discussed. (author). 3 figs., 6 tabs., 38 refs

  9. Sporadic nocturnal frontal lobe epilepsy: A consecutive series of 8 cases

    Directory of Open Access Journals (Sweden)

    Shih-Bin Yeh

    2014-09-01

    Discussion: These cases confirm that sporadic NFLE closely resembles familial NFLE, and comprises a set of distinct clinical manifestations, with variable intensity, and variable scalp EEG epileptiform abnormalities across sleep and wakefulness, which have previously been identified in Caucasian patients from Europe and North America.

  10. CSF Neurofilament Proteins Levels are Elevated in Sporadic Creutzfeldt-Jakob Disease

    NARCIS (Netherlands)

    van Eijk, Jeroen J. J.; van Everbroeck, Bart; Abdo, W. Farid; Kremer, Berry P. H.; Verbeek, Marcel M.

    2010-01-01

    In this study we investigated the cerebrospinal fluid (CSF) levels of neurofilament light (NFL) and heavy chain (NFHp35), total tau (t-tau), and glial fibrillary acidic protein (GFAP) to detect disease specific profiles in sporadic Creutzfeldt Jakob disease (sCJD) patients and Alzheimer's disease

  11. Modelling the effects of penetrance and family size on rates of sporadic and familial disease.

    Science.gov (United States)

    Al-Chalabi, Ammar; Lewis, Cathryn M

    2011-01-01

    Many complex diseases show a diversity of inheritance patterns ranging from familial disease, manifesting with autosomal dominant inheritance, through to simplex families in which only one person is affected, manifesting as apparently sporadic disease. The role of ascertainment bias in generating apparent patterns of inheritance is often overlooked. We therefore explored the role of two key parameters that influence ascertainment, penetrance and family size, in rates of observed familiality. We develop a mathematical model of familiality of disease, with parameters for penetrance, mutation frequency and family size, and test this in a complex disease: amyotrophic lateral sclerosis. Monogenic, high-penetrance variants can explain patterns of inheritance in complex diseases and account for a large proportion of those with no apparent family history. With current demographic trends, rates of familiality will drop further. For example, a variant with penetrance 0.5 will cause apparently sporadic disease in 12% of families of size 10, but 80% of families of size 1. A variant with penetrance 0.9 has only an 11% chance of appearing sporadic in families of a size similar to those of Ireland in the past, compared with 57% in one-child families like many in China. These findings have implications for genetic counselling, disease classification and the design of gene-hunting studies. The distinction between familial and apparently sporadic disease should be considered artificial. Copyright © 2011 S. Karger AG, Basel.

  12. Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature

    Directory of Open Access Journals (Sweden)

    Nozières Cécile

    2011-10-01

    Full Text Available Abstract Background Somatotropinoma, a pituitary adenoma characterised by excessive production of growth hormone (GH, is extremely rare in childhood. A genetic defect is evident in some cases; known genetic changes include: multiple endocrine neoplasia type 1 (MEN1; Carney complex; McCune-Albright syndrome; and, more recently identified, aryl hydrocarbon receptor-interacting protein (AIP. We describe seven children with somatotropinoma with a special focus on the differences between genetic and sporadic forms. Methods Seven children who presented in our regional network between 1992 and 2008 were included in this retrospective analysis. First-type therapy was somatostatin (SMS analogues or transsphenoidal surgery. Control was defined as when insulin-like growth factor-1 (IGF-1 levels were within the normal range for the patient's age at 6 months after therapy, associated with decreasing tumour volume. Results Patients were aged 5-17 years and the majority (n = 6 were male. Four patients had an identified genetic mutation (McCune-Albright syndrome: n = 1; MEN1: n = 1; AIP: n = 2; the remaining three cases were sporadic. Accelerated growth rate was reported as the first clinical sign in four patients. Five patients presented with macroadenoma; invasion was noted in four of them (sporadic: n = 1; genetic: n = 3. Six patients were treated with SMS analogues; normalisation of IGF-1 occurred in one patient who had a sporadic intrasellar macroadenoma. Multiple types of therapy were necessary in all patients with an identified genetic mutation (4 types: n = 1; 3 types: n = 2; 2 types: n = 1, whereas two of the three patients with sporadic somatotropinoma required only one type of therapy. Conclusions This is the first series that analyzes the therapeutic response of somatotropinoma in paediatric patients with identified genetic defects. We found that, in children, genetic somatotropinomas are more invasive than sporadic somatotropinomas. Furthermore

  13. Diffusion MR imaging in sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    Burcak Cakir Pekoz

    2014-08-01

    Full Text Available Creutzfeldt-Jakob disease (CJD is a rare dementing disease and is thought to caused by a prion. It is characterized by rapidly progressive dementia, ataxia, myoclonus, akinetic mutism and eventual death. Brain biopsy or autopsy is required for a definitive diagnosis of CJD. Diffusion-weighted imaging became an important tool for early diagnosis of CJD because of the high sensitivity. We present 59-year-old female patient diagnosed as sporadic CJD with typical MR imagings. [Cukurova Med J 2014; 39(4.000: 880-883

  14. Cognitive disorders after sporadic ecstasy use? A case report.

    Science.gov (United States)

    Ruis, Carla; Postma, Albert; Bouvy, Willem; van der Ham, Ineke

    2015-01-01

    Memory problems and changes in hippocampal structures after chronic ecstasy use are well described in the literature. Cognitive problems after incidental ecstasy use are rare, and the few patients described in case reports returned to their normal cognitive level after a relative short period. FV is a 39-year-old man who used an ecstasy tablet in 2005. This resulted in severe confusion for a few days. The confusion was followed by persistent memory complaints and difficulties orientating in new surroundings. An extensive neuropsychological examination 7 years after the ecstasy use revealed a severe memory disorder. Furthermore, his performance on a virtual reality test of navigation showed serious problems navigating in new surroundings. In comparison with matched control subjects (Bayesian approach for single case studies) his scores were significantly impaired on several subtasks of the navigation test. On a magnetic resonance imaging (MRI) scan of the brain bilateral hippocampal atrophy and sclerosis were visible, comparable to previous MRI studies describing hippocampal damage following ecstasy ingestion. This case report describes persistent memory and navigation disorders after sporadic ecstasy use, supported by structural brain abnormalities seen on the MRI scan. These findings revive the debate on whether sporadic ecstasy use can cause persistent cognitive deficits.

  15. Comparison between hearing screening-detected cases and sporadic cases of delayed-onset hearing loss in preschool-age children.

    Science.gov (United States)

    Lü, Jingrong; Huang, Zhiwu; Ma, Yan; Li, Yun; Mei, Ling; Yao, Guoyin; Wang, Yu; Shen, Xiaoming; Wu, Hao

    2014-04-01

    This study aimed to compare the diagnosis and ages of intervention for cases of delayed-onset hearing loss identified sporadically or via a preschool hearing screening program. Retrospective study with the comparative analysis of two groups of children. Cases identified from screening were selected from 34 321 preschool children who underwent screening for delayed-onset hearing loss between October 2009 and May 2011. Sporadic cases of delayed-onset hearing loss were selected from pediatric clinical records. Cases from the first group were excluded from the latter to avoid duplication. Two groups were given the same questionnaire to record risk indicators, diagnosis, and age at intervention. The average age of 26 children at the time of diagnosis in the screening group (52.81 ± 13.23 months) was significantly earlier than in the 33 cases identified in the sporadic group (62.03 ± 12.86 months; p children with bilateral moderate to severe hearing loss in the screening group (50.40 ± 10.76 months) was also earlier than in the sporadic group (62.73 ± 13.77 months; p hearing screening for preschool children with no significant symptoms of delayed-onset hearing loss.

  16. Is syndromic data from rural poultry farmers a viable poultry disease reporting tool and means of identifying likely farmer responses to poultry disease incursion?

    Science.gov (United States)

    Mubamba, C; Ramsay, G; Abolnik, C; Dautu, G; Gummow, B

    2018-05-01

    Syndromic surveillance is a well described tool used in developed countries for alerting authorities to livestock disease incursions. However, little work has been done to evaluate whether this could be a viable tool in countries where disease reporting infrastructure and resources is poor. Consequently, a syndrome-based questionnaire study in Eastern Zambia was designed to gather data on previous encounters farmers had with poultry diseases, as well as control measures they use to mitigate them. Descriptive statistics and logistic regression were used to analyse the data. Farmers reported an overall annual disease incidence in rural poultry for eastern Zambia of 31% (90% CI 29-32%). Occurrence of poultry disease in the last 12 months was associated with use of middlemen to purchase poultry products (p = 0.05, OR = 7.87), poultry products sold or given away from the farm (p = 0.01, OR = 1.92), farmers experiencing a period with more trade of poultry and its products (p = 0.04, OR = 1.70), presence of wild birds near the farm or village (p = 0.00, OR = 2.47) and poultry diseases being reported from neighbouring farms or villages (p = 0.00, OR = 3.12). The study also tentatively identified three poultry diseases (Newcastle Disease, Gumboro Disease and Fowl Pox) from the thirty-four disease syndromes provided by farmers. Farmers reported an incidence of 27% for Newcastle Disease in 2014. When compared with the state veterinary services data which reported Newcastle Disease incidence at 9% in 2014, it seems syndromic data obtained from farmers may be more sensitive in identifying disease incursion. Thirty-six remedies and strategies farmers use to treat and control these diseases were revealed. The main control strategy for identified diseases was vaccination and the main treatment was unspecified herbs, which warrants further investigation and presents an opportunity for further research in ethno-veterinary medicine. More still

  17. S182 and STM2 gene missense mutations in sporadic alzheimer disease

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Susumu; Matsushita, Sachio; Hasegawa, Yoshio; Muramatsu, Taro [Kurihama National Hospital, Yokosuka (Japan)] [and others

    1996-07-26

    The linkage of genes S182 and STM2 to early-onset or late-onset sporadic Alzheimer disease (AD) was not found in a group of 97 clinically-diagnosed AD patients and 46 autopsy-confirmed AD cases, using PCR-RFLP methods. 7 refs.

  18. Anorectal function and morphology in patients with sporadic proctalgia fugax.

    Science.gov (United States)

    Eckardt, V F; Dodt, O; Kanzler, G; Bernhard, G

    1996-07-01

    The pathophysiology of sporadic proctalgia fugax remains unknown. This study investigates whether patients with this syndrome exhibit alterations in anal function and morphology. Eighteen patients with sporadic proctalgia fugax and 18 sex-matched and age-matched healthy controls were studied. Manometric studies investigated anal resting and squeeze pressures, the rectoanal inhibitory reflex, rectal compliance, and smooth muscle response to edrophonium chloride administration. External and internal sphincter thickness was measured endosonographically. Patients had slightly higher (P = 0.0291) anal resting pressures (65.5 +/- 11.4 mmHg) than controls (56 +/- 9.9 mmHg). However, anal squeeze pressure, sphincter relaxation during rectal distention, and rectal compliance were similar in both groups, and no alterations were detected in external and internal anal sphincter thickness. Edrophonium chloride administration was followed by sharp postrelaxation contractions in two patients, whereas anal function remained unaltered in controls. Acute episodes of proctalgia, which occurred in two patients while under study, were associated with a rise in anal resting tone and an increase in slow wave amplitude. In the resting state, patients with proctalgia fugax have normal anorectal function and morphology. However, they may exhibit a motor abnormality of the anal smooth muscle during an acute attack.

  19. Human and entomological surveillance of West Nile fever, dengue and chikungunya in Veneto Region, Italy, 2010-2012.

    Science.gov (United States)

    Gobbi, Federico; Capelli, Gioia; Angheben, Andrea; Giobbia, Mario; Conforto, Mario; Franzetti, Marzia; Cattelan, Anna Maria; Raise, Enzo; Rovere, Pierangelo; Mulatti, Paolo; Montarsi, Fabrizio; Drago, Andrea; Barzon, Luisa; Napoletano, Giuseppina; Zanella, Francesca; Pozza, Francesca; Russo, Francesca; Rosi, Paolo; Palù, Giorgio; Bisoffi, Zeno

    2014-02-05

    Since 2010 Veneto region (North-Eastern Italy) planned a special integrated surveillance of summer fevers to promptly identify cases of West Nile Fever (WNF), dengue (DENV) and chikungunya (CHIKV). The objectives of this study were (i) To increase the detection rate of imported CHIKV and DENV cases in travellers from endemic areas and promptly identify potential autochthonous cases.(ii) To detect autochthonous cases of WNF, besides those of West Nile Neuroinvasive Disease (WNND) that were already included in a national surveillance. Human surveillance: a traveler who had returned within the previous 15 days from endemic countries, with fever >38°C, absence of leucocytosis (leukocyte count 38°C for Entomologic surveillance: for West Nile (WNV) it was carried out from May through November placing CDC-CO2 traps in five provinces of Veneto Region, while for DENV and CHIKV it was also performed around residences of viremic cases. Human surveillance: between 2010 and 2012, 234 patients with fever after travelling were screened, of which 27 (11,5%) were found infected (24 with DENV and 3 with CHIKV). No autochthonous case of DENV or CHIKV was detected. Autochthonous patients screened for WNF were 408, and 24 (5,9%) were confirmed cases. Entomologic surveillance: the WNV was found in 10, 2 and 11 pools of Culex pipiens from 2010 to 2012 respectively, in sites of Rovigo, Verona, Venezia and Treviso provinces). No infected Aedes albopictus with DENV or CHIKV was found. Veneto is the only Italian region reporting WNV human cases every year since 2008. WNV is likely to cause sporadic cases and unforeseeable outbreaks for decades. Including WNF in surveillance provides additional information and possibly an early alert system. Timely detection of DENV and CHIKV should prompt vector control measures to prevent local outbreaks.

  20. MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

    International Nuclear Information System (INIS)

    Urbach, H.; Solymosi, L.; Klisch, J.; Brechtelsbauer, D.; Wolf, H.K.; Gass, S.

    1998-01-01

    To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.)

  1. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Ulrike Esslinger

    Full Text Available Dilated cardiomyopathy (DCM is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS to assess the contribution of missense variants to sporadic DCM.116,855 single nucleotide variants (SNVs were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-value<0.01. The lead-SNVs at novel loci are common and located in TTN, SLC39A8, MLIP, FLNC, ALPK3 and FHOD3. In silico fine mapping identified HSPB7 as the most likely candidate at the ZBTB17 locus. Rare variant analysis (MAF<0.01 demonstrated significant association for TTN variants only (P = 0.0085. All candidate genes but one (SLC39A8 exhibit preferential expression in striated muscle tissues and mutations in TTN, BAG3, FLNC and FHOD3 are known to cause familial cardiomyopathy. We also investigated a panel of 48 known cardiomyopathy genes. Collectively, rare (n = 228, P = 0.0033 or common (n = 36, P = 0.019 variants with elevated in silico severity scores were associated with DCM, indicating that the spectrum of genes contributing to sporadic DCM extends beyond those identified here.We identified eight loci independently associated with sporadic DCM. The functions of the best candidate genes at these loci suggest that proteostasis regulation might play a role in DCM pathophysiology.

  2. Transarterial ethanol ablation for sporadic and non-hemorrhaging angiomyolipoma in the kidney

    International Nuclear Information System (INIS)

    Takebayashi, Shigeo; Horikawa, Ayumi; Arai, Mito; Iso, Shinichiroh; Noguchi, Kazumi

    2009-01-01

    Purpose: We evaluated the efficacy and side effects of transarterial ethanol ablation in sporadic and non-hemorrhaging angiomyolipomas (AMLs) in the kidney. Material and Methods: A total of 10 patients with solitary and sporadic AMLs underwent selective transarterial absolute ethanol ablation for prophylaxis against hemorrhage. We confirmed the ratio areas of tumor vessel on angiogram, those of infraction on post-ablation computed tomography (CT) and those of tumor reduction in a 3-, 6- and 12-month follow-up CT. Results: Once or twice a single infusion of 1 or 2 ml absolute ethanol achieved in a total occlusion of 22 feeding arteries which consisted of 7 proximal interlobar arteries, 12 distal interlobar arteries and 3 renal capsular arteries. Nontarget occlusion did not occur by ethanol reflux in any cases but occurred causing spasms provoked by repeated inflation and deflation of the balloon in one case. Total occlusion of tumor vessels was observed in 7 patients and 92-95% occlusion in 3. Ethanol ablation produced 1.8-22.5% (mean 8.4 ± 6.8%) areas of infarctions but the outcome was not serious in all cases. Mean percentage areas of tumor reduction were 29.4 ± 10.6% in a 3-month follow-up, 45.7 ± 11.9% in a 6-month and 59.3 ± 11.5% in a 12-month follow-up. Conclusions: Absolute ethanol ablation for sporadic and non-hemorrhaging AML is safe and effective in reducing majority of tumor area in a 1-year follow-up.

  3. Gender- and age-dependent gamma-secretase activity in mouse brain and its implication in sporadic Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    Lisa Placanica

    Full Text Available Alzheimer disease (AD is an age-related disorder. Aging and female gender are two important risk factors associated with sporadic AD. However, the mechanism by which aging and gender contribute to the pathogenesis of sporadic AD is unclear. It is well known that genetic mutations in gamma-secretase result in rare forms of early onset AD due to the aberrant production of Abeta42 peptides, which are the major constituents of senile plaques. However, the effect of age and gender on gamma-secretase has not been fully investigated. Here, using normal wild-type mice, we show mouse brain gamma-secretase exhibits gender- and age-dependent activity. Both male and female mice exhibit increased Abeta42ratioAbeta40 ratios in aged brain, which mimics the effect of familial mutations of Presenilin-1, Presenlin-2, and the amyloid precursor protein on Abeta production. Additionally, female mice exhibit much higher gamma-secretase activity in aged brain compared to male mice. Furthermore, both male and female mice exhibit a steady decline in Notch1 gamma-secretase activity with aging. Using a small molecule affinity probe we demonstrate that male mice have less active gamma-secretase complexes than female mice, which may account for the gender-associated differences in activity in aged brain. These findings demonstrate that aging can affect gamma-secretase activity and specificity, suggesting a role for gamma-secretase in sporadic AD. Furthermore, the increased APP gamma-secretase activity seen in aged females may contribute to the increased incidence of sporadic AD in women and the aggressive Abeta plaque pathology seen in female mouse models of AD. In addition, deceased Notch gamma-secretase activity may also contribute to neurodegeneration. Therefore, this study implicates altered gamma-secretase activity and specificity as a possible mechanism of sporadic AD during aging.

  4. Spatio-Temporal Distribution of Vector-Host Contact (VHC) Ratios and Ecological Niche Modeling of the West Nile Virus Mosquito Vector, Culex quinquefasciatus, in the City of New Orleans, LA, USA.

    Science.gov (United States)

    Sallam, Mohamed F; Michaels, Sarah R; Riegel, Claudia; Pereira, Roberto M; Zipperer, Wayne; Lockaby, B Graeme; Koehler, Philip G

    2017-08-08

    The consistent sporadic transmission of West Nile Virus (WNV) in the city of New Orleans justifies the need for distribution risk maps highlighting human risk of mosquito bites. We modeled the influence of biophysical and socioeconomic metrics on the spatio-temporal distributions of presence/vector-host contact (VHC) ratios of WNV vector, Culex quinquefasciatus , within their flight range . Biophysical and socioeconomic data were extracted within 5-km buffer radii around sampling localities of gravid female Culex quinquefasciatus . The spatio-temporal correlations between VHC data and 33 variables, including climate, land use-land cover (LULC), socioeconomic, and land surface terrain were analyzed using stepwise linear regression models (RM). Using MaxEnt, we developed a distribution model using the correlated predicting variables. Only 12 factors showed significant correlations with spatial distribution of VHC ratios ( R ² = 81.62, p < 0.01). Non-forested wetland (NFWL), tree density (TD) and residential-urban (RU) settings demonstrated the strongest relationship. The VHC ratios showed monthly environmental resilience in terms of number and type of influential factors. The highest prediction power of RU and other urban and built up land (OUBL), was demonstrated during May-August. This association was positively correlated with the onset of the mosquito WNV infection rate during June. These findings were confirmed by the Jackknife analysis in MaxEnt and independently collected field validation points. The spatial and temporal correlations of VHC ratios and their response to the predicting variables are discussed.

  5. Health professions and risk of sporadic Creutzfeldt- Jakob disease, 1965 to 2010

    NARCIS (Netherlands)

    E. Alcalde-Cabero; J. Almazán-Isla; J-P. Brandel (Jean-Philippe); M. Breithaupt; J. Catarino; S.J. Collins (Steven); J. Haybäck; R. Höftberger (Romana); E. Kahana; G.G. Kovacs (Gabor); A. Ladogana (Anna); E. Mitrová (Eva); A. Molesworth; Y. Nakamura; M. Pocchiari (Maurizio); M. Popovic; M. Ruiz-Tovar; A. Taratuto; C. van Duin; M. Yamada; R.G. Will (Robert); I. Zerr (Inga); J. de Pedro-Cuesta (Jesús)

    2012-01-01

    textabstractIn 2009, a pathologist with sporadic Creutzfeldt- Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network

  6. TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin Inclusions

    NARCIS (Netherlands)

    Cairns, Nigel J.; Neumann, Manuela; Bigio, Eileen H.; Holm, Ida E.; Troost, Dirk; Hatanpaa, Kimmo J.; Foong, Chan; White, Charles L.; Schneider, Julie A.; Kretzschmar, Hans A.; Carter, Deborah; Taylor-Reinwald, Lisa; Paulsmeyer, Katherine; Strider, Jeffrey; Gitcho, Michael; Goate, Alison M.; Morris, John C.; Mishrall, Manjari; Kwong, Linda K.; Stieber, Anna; Xu, Yan; Forman, Mark S.; Trojanowski, John Q.; Lee, Virginia M.-Y.; Mackenzie, Ian R. A.

    2007-01-01

    TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a novel class of neurodegenerative diseases called

  7. Planetary and tidal wave-type oscillations in the ionospheric sporadic E layers over Tehran region

    Science.gov (United States)

    Karami, K.; Ghader, S.; Bidokhti, A. A.; Joghataei, M.; Neyestani, A.; Mohammadabadi, A.

    2012-04-01

    It is believed that in the lower ionosphere, particularly in the ionospheric sporadic E (Es) layers (90-130 km), the planetary and tidal wave-type oscillations in the ionized component indicate the planetary and tidal waves in the neutral atmosphere. In the present work, the presence of wave-type oscillations, including planetary and tidal waves in the ionospheric sporadic E layers over Tehran region is examined. Data measured by a digital ionosonde at the ionospheric station of the Institute of Geophysics, University of Tehran, from July 2006 to June 2007 are used to investigate seasonal variations of planetary and tidal waves activities. For the purpose of accurate comparison between different seasons, wavelet transform is applied to time series of foEs and h‧Es, namely, the critical frequency and virtual height of Es layers, respectively. The results show that the sporadic E layers over Tehran region are strongly under the influence of upward propagation of waves from below. More specifically, among diverse range of periodicities in the sporadic E layers, we found that diurnal (24 hours) and semidiurnal (12 hours) oscillations in all seasons for both parameters. Moreover, terdiurnal (8 hours) tide-like variation is observed during spring and summer for foEs parameter and summer and winter for h‧Es. Furthermore, the results show that diurnal tidal waves obtain their maximum activities during autumn and winter seasons, and their activities decrease during the late spring and summer. In addition, periods of about 2, 4, 6, 10, 14, and 16 days in our observation verifies the hypothesis of upward propagation of planetary waves from lower atmosphere to the ionosphere. Moreover, planetary waves have their maximum activities during equinox.

  8. BRCA1 and BRCA2 Gene Mutations Screening In Sporadic Breast Cancer Patients In Kazakhstan.

    Directory of Open Access Journals (Sweden)

    Ainur R. Akilzhanova

    2013-05-01

    Full Text Available Background: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women. Aim: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer. Methods: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases and 112 age-matched controls using automatic direct sequencing. Results: We identified 22 distinct variants, including 16 missense mutations and 6 polymorphisms in BRCA1/2 genes. In BRCA1, 9 missense mutations and 3 synonymous polymorphisms were observed. In BRCA2, 7 missense mutations and 3 polymorphisms were detected. There was a higher prevalence of observed mutations in Caucasian breast cancer cases compared to Asian cases (p<0.05; higher frequencies of sequence variants were observed in Asian controls. No recurrent or founder mutations were observed in BRCA1/2 genes. There were no statistically significant differences in age at diagnosis, tumor histology, size of tumor, and lymph node involvement between women with breast cancer with or without the BRCA sequence alterations. Conclusions: Considering the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of BRCA1/2 mutations and reliable genetic counseling for Kazakhstan sporadic breast cancer patients. Evaluation of common polymorphisms and mutations and breast cancer risk in families with genetic predisposition to breast cancer is ongoing in another current investigation. 

  9. Occurrence of the blanketing sporadic E layer during the recovery phase of the October 2003 superstorm

    Science.gov (United States)

    Denardini, Clezio Marcos; Resende, Laysa Cristina Araújo; Moro, Juliano; Chen, Sony Su

    2016-05-01

    We have routinely monitored the total frequency ( ftEs) and the blanketing frequency ( fbEs) of sporadic E layers with the digital sounder under the magnetic equator in the Brazilian sector. Sporadic layers appear in the equatorial region (Esq) at heights between 90 and 130 km, mainly due to irregularities in the equatorial electrojet current. However, during the recovery phase of the October 2003 superstorm, an anomalous intensification of the ionospheric density that exceeded the normal ambient background values for local time and location was observed. The parameter fbEs rose to almost 7.5 MHz during this event, due to a type "c" blanketing sporadic layer (Esc), which is driven by wind shear. This result is discussed in terms of the atmosphere dynamics based on magnetic signature of the equatorial electrojet current using magnetometer data. Also, using data measured by sensors onboard the Geostationary Operational Environmental Satellite (GOES) 10 we analyze the possible influence of the solar flare-associated X-ray flux as an additional source of ionization.

  10. MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H.; Solymosi, L. [Department of Neuroradiology, University of Wuerzburg (Germany); Klisch, J.; Brechtelsbauer, D. [Department of Neuroradiology, University of Bonn, Bonn (Germany); Wolf, H.K. [Department of Neuropathology, University of Bonn, Bonn (Germany); Gass, S. [Department of Neurology, University of Bonn, Bonn (Germany)

    1998-02-01

    To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.) With 5 figs., 2 tabs., 23 refs.

  11. Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

    Science.gov (United States)

    Moura, M M; Cavaco, B M; Pinto, A E; Domingues, R; Santos, J R; Cid, M O; Bugalho, M J; Leite, V

    2009-01-01

    Screening of REarranged during Transfection (RET) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET-positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10–16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence (P=0.0051) and number of lymph node metastases (P=0.0017), and presented more often multifocal tumours (P=0.037) and persistent disease at last control (P=0.0242) than group 2. Detectable serum calcitonin levels at last screening (P=0.0119) and stage IV disease (P=0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk. PMID:19401695

  12. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases

    DEFF Research Database (Denmark)

    Ferrari, Raffaele; Wang, Yunpeng; Vandrovcova, Jana

    2017-01-01

    BACKGROUND: Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap between...

  13. Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients

    Directory of Open Access Journals (Sweden)

    Hanae Takatsuki, PhD

    2016-10-01

    Full Text Available Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 106/g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 106/g SD50 did not exist the infectivity.

  14. Glycoform-selective prion formation in sporadic and familial forms of prion disease

    NARCIS (Netherlands)

    Xiao, X.; Yuan, J.; Haïk, S.; Cali, I.; Zhan, Y.; Moudjou, M.; Li, B.; Laplanche, J.L.; Laude, H.; Langeveld, J.P.M.; Gambetti, P.

    2013-01-01

    The four glycoforms of the cellular prion protein (PrP(C)) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrP(Sc)) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrP(Sc) in the recently identified

  15. Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

    Science.gov (United States)

    Alves, Chrystian J.; Dariolli, Rafael; Jorge, Frederico M.; Monteiro, Matheus R.; Maximino, Jessica R.; Martins, Roberto S.; Strauss, Bryan E.; Krieger, José E.; Callegaro, Dagoberto; Chadi, Gerson

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to widespread motor neuron death, general palsy and respiratory failure. The most prevalent sporadic ALS form is not genetically inherited. Attempts to translate therapeutic strategies have failed because the described mechanisms of disease are based on animal models carrying specific gene mutations and thus do not address sporadic ALS. In order to achieve a better approach to study the human disease, human induced pluripotent stem cell (hiPSC)-differentiated motor neurons were obtained from motor nerve fibroblasts of sporadic ALS and non-ALS subjects using the STEMCCA Cre-Excisable Constitutive Polycistronic Lentivirus system and submitted to microarray analyses using a whole human genome platform. DAVID analyses of differentially expressed genes identified molecular function and biological process-related genes through Gene Ontology. REVIGO highlighted the related functions mRNA and DNA binding, GTP binding, transcription (co)-repressor activity, lipoprotein receptor binding, synapse organization, intracellular transport, mitotic cell cycle and cell death. KEGG showed pathways associated with Parkinson's disease and oxidative phosphorylation, highlighting iron homeostasis, neurotrophic functions, endosomal trafficking and ERK signaling. The analysis of most dysregulated genes and those representative of the majority of categorized genes indicates a strong association between mitochondrial function and cellular processes possibly related to motor neuron degeneration. In conclusion, iPSC-derived motor neurons from motor nerve fibroblasts of sporadic ALS patients may recapitulate key mechanisms of neurodegeneration and may offer an opportunity for translational investigation of sporadic ALS. Large gene profiling of differentiated motor neurons from sporadic ALS patients highlights mitochondrial participation in the establishment of autonomous mechanisms associated with sporadic ALS

  16. A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

    NARCIS (Netherlands)

    Wills, A-M.; Cronin, S.; Slowik, A.; Kasperaviciute, D.; Van Es, M. A.; Morahan, J. M.; Valdmanis, P. N.; Meininger, V.; Melki, J.; Shaw, C. E.; Rouleau, G. A.; Fisher, E. M. C.; Shaw, P. J.; Morrison, K. E.; Pamphlett, R.; Van den Berg, L. H.; Figlewicz, D. A.; Andersen, P. M.; Al-Chalabi, A.; Hardiman, O.; Purcell, S.; Landers, J. E.; Brown, R. H.

    2009-01-01

    Background: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding. Methods: We

  17. Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Es, M.A. van; Vught, P.W. van; Veldink, J.H.; Andersen, P.M.; Birve, A.; Lemmens, R.; Cronin, S.; Kooi, A.J. van der; Visser, M. de; Schelhaas, H.J.; Hardiman, O.; Ragoussis, I.; Lambrechts, D.; Robberecht, W.; Wokke, J.H.J.; Ophoff, R.A.; Berg, L.H. van den

    2009-01-01

    A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS,

  18. The clinical phenotype of hereditary versus sporadic prostate cancer: HPC definition revisited

    NARCIS (Netherlands)

    Cremers, R.G.H.M.; Aben, K.K.H.; Oort, I.M. van; Sedelaar, J.P.M.; Vasen, H.F.A.; Vermeulen, S.H.; Kiemeney, L.A.L.M.

    2016-01-01

    BACKGROUND: The definition of hereditary prostate cancer (HPC) is based on family history and age at onset. Intuitively, HPC is a serious subtype of prostate cancer but there are only limited data on the clinical phenotype of HPC. Here, we aimed to compare the prognosis of HPC to the sporadic form

  19. Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis

    NARCIS (Netherlands)

    Kremer, P.H.; Koeleman, B.P.C.; Rinkel, G.J.; Diekstra, F.P.; Berg, L.H. van den; Veldink, J.H.; Klijn, C.J.M.

    2016-01-01

    BACKGROUND: Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations

  20. Mechanism for the formation of sporadic-E layers in the high-latitude ionosphere

    Energy Technology Data Exchange (ETDEWEB)

    Vlasov, M.N.; Mishin, E.V.; Telegin, V.A.

    1980-09-01

    A model of the collective interaction of precipitating electrons and the ionospheric plasma is used to explain the formation of short-duration sporadic-E layers in the high-latitude ionosphere. The changes produced in electron density by this collective interaction mechanism are considered.

  1. Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia.

    Science.gov (United States)

    Tischkowitz, M D; Morgan, N V; Grimwade, D; Eddy, C; Ball, S; Vorechovsky, I; Langabeer, S; Stöger, R; Hodgson, S V; Mathew, C G

    2004-03-01

    Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder caused by mutations in one of seven known genes (FANCA,C,D2,E,F,G and BRCA2). Mutations in the FANCA gene are the most prevalent, accounting for two-thirds of FA cases. Affected individuals have greatly increased risks of acute myeloid leukemia (AML). This raises the question as to whether inherited or acquired mutations in FA genes might be involved in the development of sporadic AML. Quantitative fluorescent PCR was used to screen archival DNA from sporadic AML cases for FANCA deletions, which account for 40% of FANCA mutations in FA homozygotes. Four heterozygous deletions were found in 101 samples screened, which is 35-fold higher than the expected population frequency for germline FANCA deletions (PFANCA in the AML samples with FANCA deletions did not detect mutations in the second allele and there was no evidence of epigenetic silencing by hypermethylation. However, real-time quantitative PCR analysis in these samples showed reduced expression of FANCA compared to nondeleted AML samples and to controls. These findings suggest that gene deletions and reduced expression of FANCA may be involved in the promotion of genetic instability in a subset of cases of sporadic AML.

  2. Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients.

    Science.gov (United States)

    Takatsuki, Hanae; Fuse, Takayuki; Nakagaki, Takehiro; Mori, Tsuyoshi; Mihara, Ban; Takao, Masaki; Iwasaki, Yasushi; Yoshida, Mari; Murayama, Shigeo; Atarashi, Ryuichiro; Nishida, Noriyuki; Satoh, Katsuya

    2016-10-01

    Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 10 6 /g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 10 6 /g SD50 did not exist the infectivity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Temporal evolution of the HF-enhanced plasma line in sporadic E

    International Nuclear Information System (INIS)

    Djuth, F.T.; Gonzales, C.A.

    1988-01-01

    The high-power, high-frequency (HF) facility at Arecibo, Puerto Rico, has been used to study the excitation of Langmuir waves in mid-latitude sporadic E. Measurements of the temporal evolution of so-called HF-enhanced plasma line (HFPL) were made using the Arecibo 430-MHz radar. After HF turn-on in the plasma the HFPL exhibits a rapid growth phase followed by a quick overshoot. During periods of strong HFPL excitation the e-folding growth time of the HFPL power is typically approx-lt 20 μs, and the total overshoot period is ∼1 ms. On the basis of the current observations, mode conversion of the HF wave into Langmuir waves near HF reflection appears to be a promising mechanism for the production of Langmuir waves in sporadic E. Caviton formation at the critical layer is expected to accompany this process, and there is some evidence that the 430-MHz radar is probing the plasma in a region where density cavities of this nature form. While no specific explanation is offered for the HFPL overshoot, it appears that this phenomenon is fundamental to the Langmuir wave excitation process

  4. Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Statland, Jeffrey M; Barohn, Richard J; McVey, April L; Katz, Jonathan S; Dimachkie, Mazen M

    2015-11-01

    When approaching a patient with suspected motor neuron disease (MND), the pattern of weakness on examination helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing. MNDs exist on a spectrum, from a pure lower motor neuron to mixed upper and lower motor neuron to a pure upper motor neuron variant. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic, which is invariably fatal. This article describes a pattern approach to identifying MND and clinical features of sporadic ALS. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Seasonal variability and descent of mid-latitude sporadic E layers at Arecibo

    Directory of Open Access Journals (Sweden)

    N. Christakis

    2009-03-01

    Full Text Available Sporadic E layers (Es follow regular daily patterns in variability and altitude descent, which are determined primarily by the vertical tidal wind shears in the lower thermosphere. In the present study a large set of sporadic E layer incoherent scatter radar (ISR measurements are analyzed. These were made at Arecibo (Geog. Lat. ~18° N; Magnetic Dip ~50° over many years with ISR runs lasting from several hours to several days, covering evenly all seasons. A new methodology is applied, in which both weak and strong layers are clearly traced by using the vertical electron density gradient as a function of altitude and time. Taking a time base equal to the 24-h local day, statistics were obtained on the seasonal behavior of the diurnal and semidiurnal tidal variability and altitude descent patterns of sporadic E at Arecibo. The diurnal tide, most likely the S(1,1 tide with a vertical wavelength around 25 km, controls fully the formation and descent of the metallic Es layers at low altitudes below 110 km. At higher altitudes, there are two prevailing layers formed presumably by vertical wind shears associated mainly with semidiurnal tides. These include: 1 a daytime layer starting at ~130 km around midday and descending down to 105 km by local midnight, and 2 a less frequent and weaker nighttime layer which starts prior to midnight at ~130 km, descending downwards at somewhat faster rate to reach 110 km by sunrise. The diurnal and semidiurnal-like pattern prevails, with some differences, in all seasons. The differences in occurrence, strength and descending speeds between the daytime and nighttime upper layers are not well understood from the present data alone and require further study.

  6. Sporadic manipulation in money markets with central bank standing facilities

    OpenAIRE

    Ewerhart, Christian; Cassola, Nuno; Ejerskov, Steen; Valla, Natacha

    2004-01-01

    In certain market environments, a large investor may benefit from building up a futures position first and trading subsequently in the spot market (Kumar and Seppi, 1992). The present paper identifies a variation of this type of manipulation that might occur in money markets with an interest rate corridor. We show that manipulation involving the use of central bank facilities would be observable only sporadically. The probability of manipulation decreases when the central bank uses an active ...

  7. Sporadic sodium and E layers observed during the summer 2002 MaCWAVE/MIDAS rocket campaign

    Directory of Open Access Journals (Sweden)

    B. P. Williams

    2006-07-01

    Full Text Available On 5 July 2002, a MaCWAVE (Mountain and Convective Waves Ascending VErtically payload launched from Andøya Rocket Range, Norway, observed narrow enhanced layers of electron density that were nearly coincident with sporadic sodium layers measured by the Weber sodium lidar at the nearby ALOMAR Observatory. We investigate the formation mechanism of these layers using the neutral wind and temperature profiles measured directly by the lidar and the vertical motion deduced from the sodium mixing ratio. Through comparisons of the lidar data to the sporadic E in situ data, we find support for the concentration and downward motion of ions to an altitude where chemical models predict the rapid conversion of sodium ions to neutral sodium.

  8. A Tangled Web - Tau and Sporadic Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Selina Wray

    2010-12-01

    Full Text Available Parkinson's disease (PD represents a major challenge for health care systems around the world: it is the most common degenerative movement disorder of old age, affecting over 100,000 people in the UK alone. A great deal of progress has been made in understanding the molecular basis of PD by taking advantage of advances in genetics, initially by the identification of genes responsible for rare mendellian forms of PD (outlined in table one, and more recently by applying genome wide association studies (GWAS to the sporadic form of the disease. Several such GWAS have now been carried out, with a meta-analysis currently under way. Using over 6000 cases and 10000 controls, two of these studies have identified variation at a number of loci as being associated with an increased risk of disease. Three genes stand out as candidates from these studies – the SNCA gene, coding for α -synuclein, the LRRK2 gene, coding for leucine rich repeat kinase 2, and MAPT, coding for the microtubule associated protein tau. Point mutations in α -synuclein, along with gene multiplication events, result in autosomal dominant PD, often with a significant dementia component. In addition to this, α -synuclein is the principle component of the main pathological hallmark of PD, the Lewy body. Mutations in LRRK2 are the most common genetic cause of PD, and so again were a likely candidate for a susceptibility locus for the sporadic form of disease. More surprising, perhaps, was the identification of tau as a susceptibility factor for Parkinson's. In this review we will outline the role of tau in neurodegeneration and in different forms of parkinsonism, and speculate as to what the functional basis of this association might be.

  9. Agraphia of Kanji (Chinese characters): an early symptom of sporadic Creutzfeldt-Jakob disease in a Japanese patient: a case report.

    Science.gov (United States)

    Nakamura, Keiko; Sakai, Kenji; Samuraki, Miharu; Nozaki, Ichiro; Notoya, Masako; Yamada, Masahito

    2014-08-06

    Slowly progressive cognitive decline is the most frequent initial manifestation in MM2-cortical-type sporadic Creutzfeldt-Jakob disease. Agraphia has never been noted in patients with this type of sporadic Creutzfeldt-Jakob disease, however, we report the case of a Japanese patient with sporadic Creutzfeldt-Jakob disease in whom agraphia of Kanji was an initial cardinal symptom. A 59-year-old right-handed Japanese woman complained of agraphia of Kanji (Chinese characters) as an initial symptom. A neurological examination revealed mild word-finding difficulty, constructive disturbance, hyperreflexia in her jaw and lower limbs, and bilateral extensor plantar reflexes. An examination of her cerebrospinal fluid revealed increased levels of 14-3-3 and total tau proteins, and abnormal conformation of the proteinase K-resistant prion protein. Diffusion-weighted magnetic resonance imaging showed diffuse hyperintensity in bilateral cerebral cortices. Single-photon emission computed tomography scans revealed hypoperfusion in the left temporal lobe, bilateral parietal and occipital lobes. An analysis of the prion protein gene demonstrated no mutation with homozygous for methionine at the codon 129. We diagnosed our patient with sporadic Creutzfeldt-Jakob disease. Although a histological examination was not performed, it was assumed that our patient could be the MM2-cortical type according to the clinical findings and the elevated levels of 14-3-3 protein in her cerebrospinal fluid. The left posterior inferior temporal area, which was affected in our patient as a hypoperfusion area, is associated with selecting and recalling Kanji characters. Focal signs as an early symptom and hypoperfusion areas in sporadic Creutzfeldt-Jakob disease are critical to recognize initial brain lesions damaged by the proteinase K-resistant prion protein accumulation.

  10. Electric field measurements of DC and long wavelength structures associated with sporadic-E layers and QP radar echoes

    Directory of Open Access Journals (Sweden)

    S. Ohtsuki

    2005-10-01

    Full Text Available Electric field and plasma density data gathered on a sounding rocket launched from Uchinoura Space Center, Japan, reveal a complex electrodynamics associated with sporadic-E layers and simultaneous observations of quasi-periodic radar echoes. The electrodynamics are characterized by spatial and temporal variations that differed considerably between the rocket's upleg and downleg traversals of the lower ionosphere. Within the main sporadic-E layer (95–110 km on the upleg, the electric fields were variable, with amplitudes of 2–4 mV/m that changed considerably within altitude intervals of 1–3 km. The identification of polarization electric fields coinciding with plasma density enhancements and/or depletions is not readily apparent. Within this region on the downleg, however, the direction of the electric field revealed a marked change that coincided precisely with the peak of a single, narrow sporadic-E plasma density layer near 102.5 km. This shear was presumably associated with the neutral wind shear responsible for the layer formation. The electric field data above the sporadic-E layer on the upleg, from 110 km to the rocket apogee of 152 km, revealed a continuous train of distinct, large scale, quasi-periodic structures with wavelengths of 10–15 km and wavevectors oriented between the NE-SW quadrants. The electric field structures had typical amplitudes of 3–5 mV/m with one excursion to 9 mV/m, and in a very general sense, were associated with perturbations in the plasma density. The electric field waveforms showed evidence for steepening and/or convergence effects and presumably had mapped upwards along the magnetic field from the sporadic-E region below. Candidate mechanisms to explain the origin of these structures include the Kelvin-Helmholtz instability and the Es-layer instability. In both cases, the same shear that formed the sporadic-E layer would provide the energy to generate the km-scale structures. Other possibilities

  11. Height and critical frequency variations of the sporadic-E layer at midlatitudes

    Czech Academy of Sciences Publication Activity Database

    Šauli, Petra; Bourdillon, A.

    2008-01-01

    Roč. 70, č. 15 (2008), s. 1904-1910 ISSN 1364-6826 R&D Projects: GA AV ČR IAA300420704 Grant - others:European Union(XE) COST 296 Institutional research plan: CEZ:AV0Z30420517 Keywords : Sporadic E * Planetary waves * Tidal waves * Mid-latitude ionosphere * Wavelet transform Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.667, year: 2008

  12. Aberrant gene promoter methylation associated with sporadic multiple colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Victoria Gonzalo

    Full Text Available BACKGROUND: Colorectal cancer (CRC multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2, RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008 and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047 as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006. Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17, SFRP1 (r = 0.83, 0.06, HPP1 (r = 0.64, p = 0.17, 3OST2 (r = 0.83, p = 0.06 and GATA4 (r = 0.6, p = 0.24. Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant

  13. Specific deficit of colour-colour short-term memory binding in sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Parra, Mario A; Sala, Sergio Della; Abrahams, Sharon; Logie, Robert H; Méndez, Luis Guillermo; Lopera, Francisco

    2011-06-01

    Short-term memory binding of visual features which are processed across different dimensions (shape-colour) is impaired in sporadic Alzheimer's disease, familial Alzheimer's disease, and in asymptomatic carriers of familial Alzheimer's disease. This study investigated whether Alzheimer's disease also impacts on within-dimension binding processes. The study specifically explored whether visual short-term memory binding of features of the same type (colour-colour) is sensitive to Alzheimer's disease. We used a neuropsychological battery and a short-term memory binding task to assess patients with sporadic Alzheimer's disease (Experiment 1), familial Alzheimer's disease (Experiment 2) due to the mutation E280A of the Presenilin-1 gene and asymptomatic carriers of the mutation. The binding task assessed change detection within arrays of unicoloured objects (Colour Only) or bicoloured objects the colours of which had to be remembered separately (Unbound Colours) or together (Bound Colours). Performance on the Bound Colours condition (1) explained the largest proportion of variance between patients (sporadic and familial Alzheimer's disease), (2) combined more sensitivity and specificity for the disease than other more traditional neuropsychological tasks, (3) identified asymptomatic carriers of the mutation even when traditional neuropsychological measures and other measures of short-term memory did not and, (4) contrary to shape-colour binding, correlated with measures of hippocampal functions. Colour-colour binding and shape-colour binding both appear to be sensitive to AD even though they seem to rely on different brain mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes.

    Directory of Open Access Journals (Sweden)

    Michel Guipponi

    Full Text Available Schizophrenia (SCZ is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7×10(-8 per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene.

  15. Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer's model.

    Directory of Open Access Journals (Sweden)

    Zhi-Peng Xu

    Full Text Available Alzheimer's disease (AD is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP, dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3β at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3β in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy.

  16. Early detection of sporadic pancreatic cancer: strategic map for innovation--a white paper.

    Science.gov (United States)

    Kenner, Barbara J; Chari, Suresh T; Cleeter, Deborah F; Go, Vay Liang W

    2015-07-01

    Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer.

  17. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Spiegelman, Dan; McConkey, Brendan J; Vande Velde, Christine; Bouchard, Jean-Pierre; Lacomblez, Lucette; Pochigaeva, Ksenia; Salachas, Francois; Pradat, Pierre-Francois; Camu, William; Meininger, Vincent; Dupre, Nicolas; Rouleau, Guy A

    2008-05-01

    Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis.

  18. Searching for effects caused by thunderstorms in midlatitude sporadic E layers

    Czech Academy of Sciences Publication Activity Database

    Barta, V.; Haldoupis, C.; Sátori, G.; Burešová, Dalia; Chum, Jaroslav; Pozoga, M.; Berényi, K. A.; Bór, J.; Popek, Martin; Kis, Á.; Bencze, P.

    2017-01-01

    Roč. 161, August (2017), s. 150-159 ISSN 1364-6826 R&D Projects: GA ČR(CZ) GC15-07281J; GA ČR(CZ) GAP209/12/2440; GA ČR(CZ) GA14-31899S Institutional support: RVO:68378289 Keywords : atmospheric gravity waves * ionosphere coupling * lightning * sporadic E layer * sprites * thunderstorm Subject RIV: DG - Athmosphere Sciences, Meteorology OBOR OECD: Meteorology and atmospheric sciences Impact factor: 1.326, year: 2016 https://arxiv.org/abs/1708.00270

  19. Imaging and clinical characteristics of sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    HAN Shun-chang

    2013-04-01

    Full Text Available Five patients with sporadic Creutzfeldt-Jakob disease (sCJD presented rapidly progressive dementia which were subacute onset from 1 to 4 months. Among these cases, periodic synchronous discharge (PSD of electroencephalography (EEG was seen in 2 patients. Besides, 4 patients obtained positive results in cerebrospinal fluid (CSF analysis for 14-3-3 protein. The cranial MRI examination showed symmetrical or asymmetrical colored-ribbon-shaped high signals in cerebral cortex or basal ganglia by diffusion weighted imaging (DWI, suggesting that DWI had high sensitivity and specificity for the diagnosis of sCJD as a preferred method in the clinical examination of sCJD.

  20. Update on Sporadic Colorectal Cancer Genetics.

    Science.gov (United States)

    Hardiman, Karin M

    2018-05-01

    Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.

  1. Minimally Invasive Treatment of Sporadic Burkitt’s Lymphoma Causing Ileocaecal Invagination

    Directory of Open Access Journals (Sweden)

    Paolo Panaccio

    2018-01-01

    Full Text Available Introduction. Primary NHL (non-Hodgkin lymphoma of the colon represents only 0.2% to 1.2% of all colonic malignancies. Burkitt’s lymphoma (BL is usually a disease reported in children and young people, most of them associated with EBV or HIV infection. We describe a rare case of intestinal obstruction due to sporadic Burkitt’s lymphoma causing ileocaecal invagination explaining our experience Methods. A 31-year-old man presented with diffuse colic pain and weight loss. Clinical examination revealed an abdominal distension with pain in the right iliac fossa. Colonoscopy documented a caecal large lesion with ulcerated mucosa. Computed tomography (CT have shown a 60 × 50 mm right colic parietal lesion with signs of ileocolic intussusception. Results. Laparoscopic right hemicolectomy was performed. Postoperative period was uneventful. CD20+ high-grade B-cell Burkitt’s lymphoma was confirmed by immunohistochemistry (CD20+, CD79+, and CD10+ and FISH test (t (8;14 (q24; q32. The patient was subsequently treated with adjuvant combination chemotherapy (Hyper-CVAD and is alive and disease-free at 8 months follow-up. Discussion. Adult sporadic Burkitt’s lymphoma (BL causing intestinal obstruction due to ileocaecal intussusception is an extremely rare occurrence and a diagnostic dilemma. Despite the surgical approach is selected based on patient’s conditions and surgeon’s expertise, minimally invasive method could be preferred.

  2. The formation of sporadic E layers by a vortical perturbation excited in a horizontal wind shear flow

    Directory of Open Access Journals (Sweden)

    G. G. Didebulidze

    2008-06-01

    Full Text Available The formation of the mid-latitude sporadic E layers (Es layers by an atmospheric vortical perturbation excited in a horizontal shear flow (horizontal wind with a horizontal linear shear is investigated. A three-dimensional atmospheric vortical perturbation (atmospheric shear waves, whose velocity vector is in the horizontal plane and has a vertical wavenumber kz≠0, can provide a vertical shear of the horizontal wind. The shear waves influence the vertical transport of heavy metallic ions and their convergence into thin and dense horizontal layers. The proposed mechanism takes into account the dynamical influence of the shear wave velocity in the horizontal wind on the vertical drift velocity of the ions. It also can explain the multi-layer structure of Es layers. The pattern of the multi-layer structure depends on the value of the shear-wave vertical wavelength, the ion-neutral collision frequency and the direction of the background horizontal wind. The modelling of formation of sporadic E layers with a single and a double peak is presented. Also, the importance of shear wave coupling with short-period atmospheric gravity waves (AGWs on the variations of sporadic E layer ion density is examined and discussed.

  3. Controlling disease outbreaks in wildlife using limited culling: modelling classical swine fever incursions in wild pigs in Australia.

    Science.gov (United States)

    Cowled, Brendan D; Garner, M Graeme; Negus, Katherine; Ward, Michael P

    2012-01-16

    Disease modelling is one approach for providing new insights into wildlife disease epidemiology. This paper describes a spatio-temporal, stochastic, susceptible- exposed-infected-recovered process model that simulates the potential spread of classical swine fever through a documented, large and free living wild pig population following a simulated incursion. The study area (300 000 km2) was in northern Australia. Published data on wild pig ecology from Australia, and international Classical Swine Fever data was used to parameterise the model. Sensitivity analyses revealed that herd density (best estimate 1-3 pigs km-2), daily herd movement distances (best estimate approximately 1 km), probability of infection transmission between herds (best estimate 0.75) and disease related herd mortality (best estimate 42%) were highly influential on epidemic size but that extraordinary movements of pigs and the yearly home range size of a pig herd were not. CSF generally established (98% of simulations) following a single point introduction. CSF spread at approximately 9 km2 per day with low incidence rates (management in wildlife. An important finding was that it may only be necessary to cull or vaccinate relatively small proportions of a population to successfully contain and eradicate some wildlife disease epidemics.

  4. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome.

    Science.gov (United States)

    Wilkin, D J; Szabo, J K; Cameron, R; Henderson, S; Bellus, G A; Mack, M L; Kaitila, I; Loughlin, J; Munnich, A; Sykes, B; Bonaventure, J; Francomano, C A

    1998-01-01

    More than 97% of achondroplasia cases are caused by one of two mutations (G1138A and G1138C) in the fibroblast growth factor receptor 3 (FGFR3) gene, which results in a specific amino acid substitution, G380R. Sporadic cases of achondroplasia have been associated with advanced paternal age, suggesting that these mutations occur preferentially during spermatogenesis. We have determined the parental origin of the achondroplasia mutation in 40 sporadic cases. Three distinct 1-bp polymorphisms were identified in the FGFR3 gene, within close proximity to the achondroplasia mutation site. Ninety-nine families, each with a sporadic case of achondroplasia in a child, were analyzed in this study. In this population, the achondroplasia mutation occurred on the paternal chromosome in all 40 cases in which parental origin was unambiguous. This observation is consistent with the clinical observation of advanced paternal age resulting in new cases of achondroplasia and suggests that factors influencing DNA replication or repair during spermatogenesis, but not during oogenesis, may predispose to the occurrence of the G1138 FGFR3 mutations. PMID:9718331

  5. New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background

    Directory of Open Access Journals (Sweden)

    Marocchi Alessandro

    2008-05-01

    Full Text Available Abstract Background Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Results Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31% and from 69.1 to 86.2% (average 76.6% respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%. This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg

  6. New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

    Science.gov (United States)

    Penco, Silvana; Buscema, Massimo; Patrosso, Maria Cristina; Marocchi, Alessandro; Grossi, Enzo

    2008-05-30

    Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial

  7. Detection of infectivity in blood of persons with variant and sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Douet, Jean Yves; Zafar, Saima; Perret-Liaudet, Armand; Lacroux, Caroline; Lugan, Séverine; Aron, Naima; Cassard, Herve; Ponto, Claudia; Corbière, Fabien; Torres, Juan Maria; Zerr, Inga; Andreoletti, Olivier

    2014-01-01

    We report the presence of infectivity in erythrocytes, leukocytes, and plasma of 1 person with variant Creutzfeldt-Jakob disease and in the plasma of 2 in 4 persons whose tests were positive for sporadic Creutzfeldt-Jakob disease. The measured infectivity levels were comparable to those reported in various animals with transmissible spongiform encephalopathies.

  8. The monster sporadic group and a theory underlying superstring models

    International Nuclear Information System (INIS)

    Chapline, G.

    1996-09-01

    The pattern of duality symmetries acting on the states of compactified superstring models reinforces an earlier suggestion that the Monster sporadic group is a hidden symmetry for superstring models. This in turn points to a supersymmetric theory of self-dual and anti-self-dual K3 manifolds joined by Dirac strings and evolving in a 13 dimensional spacetime as the fundamental theory. In addition to the usual graviton and dilaton this theory contains matter-like degrees of freedom resembling the massless states of the heterotic string, thus providing a completely geometric interpretation for ordinary matter. 25 refs

  9. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    International Nuclear Information System (INIS)

    Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

    2002-01-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  10. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

    2002-04-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  11. A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk

    NARCIS (Netherlands)

    P. Sanchez-Juan (Pascual); M.T. Bishop (Matthew); G.G. Kovacs (Gabor); M. Calero (Miguel); Y.S. Aulchenko (Yurii); A. Ladogana (Anna); A. Boyd (Alison); V. Lewis (Victoria); C. Ponto (Claudia); Calero, O. (Olga); A. Poleggi (Anna); A. Carracedo (Angel); S.J. van der Lee (Sven); T. Ströbel (Thomas); F. Rivadeneira Ramirez (Fernando); A. Hofman (Albert); S. Haik; O. Combarros (Onofre); J. Berciano (José); A.G. Uitterlinden (André); S.J. Collins (Steven); H. Budka (Herbert); J-P. Brandel (Jean-Philippe); J.-L. Laplanche (Jean-Louis); M. Pocchiari (Maurizio); I. Zerr (Inga); R. Knight (Richard); R.G. Will (Robert); C.M. van Duijn (Cornelia)

    2015-01-01

    textabstractWe performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a

  12. The ‘Pokemon’ (ZBTB7) Gene: No Evidence of Association with Sporadic Breast Cancer

    Science.gov (United States)

    Salas, Antonio; Vega, Ana; Milne, Roger L.; García-Magariños, Manuel; Ruibal, Álvaro; Benítez, Javier; Carracedo, Ángel

    2008-01-01

    It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from North and Central Spanish patients. We genotyped 15 SNPs in ZBTB7, including the flanking regions, with an average coverage of 1 SNP/2.4 Kb, in 360 sporadic breast cancer cases and 402 controls. Comparison of allele, genotype and haplotype frequencies between cases and controls did not reveal associations using Pearson’s chi-square test and a permutation procedure to correct for multiple test. In this, the first study of the ZBTB7 gene in relation to, sporadic breast cancer, we found no evidence of an association. PMID:21892298

  13. Source attribution of human salmonellosis using a meta-analysis of case-control studies of sporadic infections

    DEFF Research Database (Denmark)

    Coutinho Calado Domingues, Ana Rita; Pires, Sara Monteiro; Hisham Beshara Halasa, Tariq

    2012-01-01

    Salmonella is an important cause of human illness. Disease is frequently associated with foodborne transmission, but other routes of exposure are recognized. Identifying sources of disease is essential for prioritizing public health interventions. Numerous case-control studies of sporadic salmone...

  14. Emerging therapeutic options for sporadic inclusion body myositis

    Directory of Open Access Journals (Sweden)

    Alfano LN

    2015-09-01

    Full Text Available Lindsay N Alfano, Linda P Lowes Nationwide Children’s Hospital, Center for Gene Therapy, Columbus, OH, USA Abstract: Sporadic inclusion body myositis is the most common inflammatory muscle disorder preferentially affecting males over the age of 40 years. Progressive muscle weakness of the finger flexors and quadriceps muscles results in loss of independence with activities of daily living and eventual wheelchair dependence. Initial signs of disease are often overlooked and can lead to mis- or delayed diagnosis. The underlying cause of disease is unknown, and disease progression appears refractory to available treatment options. This review discusses the clinical presentation of inclusion body myositis and the current efforts in diagnosis, and focuses on the current state of research for both nonpharmacological and pharmacological treatment options for this patient group. Keywords: myositis, inclusion body myositis, inflammatory myopathy, treatment, function, outcomes

  15. Sapflow and water use of freshwater wetland trees exposed to saltwater incursion in a tidally influenced South Carolina watershed

    Science.gov (United States)

    Krauss, K.W.; Duberstein, J.A.

    2010-01-01

    Sea-level rise and anthropogenic activity promote salinity incursion into many tidal freshwater forested wetlands. Interestingly, individual trees can persist for decades after salt impact. To understand why, we documented sapflow (Js), reduction in Js with sapwood depth, and water use (F) of baldcypress (Taxodium distichum (L.) Rich.) trees undergoing exposure to salinity. The mean Js of individual trees was reduced by 2.8 g H2O??m-2??s-1 (or by 18%) in the outer sapwood on a saline site versus a freshwater site; however, the smallest trees, present only on the saline site, also registered the lowest Js. Hence, tree size significantly influenced the overall site effect on Js. Trees undergoing perennial exposure to salt used greater relative amounts of water in outer sapwood than in inner sapwood depths, which identifies a potentially different strategy for baldcypress trees coping with saline site conditions over decades. Overall, individual trees used 100 kg H2O??day-1 on a site that remained relatively fresh versus 23.9 kg H2O??day-1 on the saline site. We surmise that perennial salinization of coastal freshwater forests forces shifts in individual-tree osmotic balance and water-use strategy to extend survival time on suboptimal sites, which further influences growth and morphology.

  16. RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers.

    Science.gov (United States)

    Fennell, Lochlan J; Clendenning, Mark; McKeone, Diane M; Jamieson, Saara H; Balachandran, Samanthy; Borowsky, Jennifer; Liu, John; Kawamata, Futoshi; Bond, Catherine E; Rosty, Christophe; Burge, Matthew E; Buchanan, Daniel D; Leggett, Barbara A; Whitehall, Vicki L J

    2018-01-01

    The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA. A validation cohort of 44 colorectal cancers from mismatch repair germline mutation carriers from the Australasian Colorectal Cancer Family Registry (ACCFR) were sequenced for the most common truncating mutation hotspots (X117 and X659). RNF43 mutations were found in 9 of 24 (37.5%) Lynch syndrome colorectal cancers. The majority of mutations were frameshift deletions in the G659 G7 repeat tract (29%); 2 cancers (2/24, 8%) from the one patient harbored frameshift mutations at codon R117 (C6 repeat tract) within exon 3. In the ACCFR validation cohort, RNF43 hotspot mutations were identified in 19/44 (43.2%) of samples, which was not significantly different to the initial series. The proportion of mutant RNF43 in Lynch syndrome related colorectal cancers is significantly lower than the previously reported mutation rate found in sporadic MSI colorectal cancers. These findings identify further genetic differences between sporadic and hereditary colorectal cancers. This may be because Lynch Syndrome cancers

  17. Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions

    DEFF Research Database (Denmark)

    de Pedro-Cuesta, Jesús; Mahillo-Fernández, Ignacio; Rábano, Alberto

    2011-01-01

    Evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains debatable in part due to misclassification of exposure levels. In a registry-based case-control study, the authors applied a risk-based classification of surgical interventions to determine the association...

  18. Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer’s disease

    Science.gov (United States)

    Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank; Buerger, Katharina; Levin, Johannes; Duering, Marco; Dichgans, Martin; Haass, Christian; Suárez-Calvet, Marc; Fagan, Anne M; Paumier, Katrina; Benzinger, Tammie; Masters, Colin L; Morris, John C; Perneczky, Robert; Janowitz, Daniel; Catak, Cihan; Wolfsgruber, Steffen; Wagner, Michael; Teipel, Stefan; Kilimann, Ingo; Ramirez, Alfredo; Rossor, Martin; Jucker, Mathias; Chhatwal, Jasmeer; Spottke, Annika; Boecker, Henning; Brosseron, Frederic; Falkai, Peter; Fliessbach, Klaus; Heneka, Michael T; Laske, Christoph; Nestor, Peter; Peters, Oliver; Fuentes, Manuel; Menne, Felix; Priller, Josef; Spruth, Eike J; Franke, Christiana; Schneider, Anja; Kofler, Barbara; Westerteicher, Christine; Speck, Oliver; Wiltfang, Jens; Bartels, Claudia; Araque Caballero, Miguel Ángel; Metzger, Coraline; Bittner, Daniel; Weiner, Michael; Lee, Jae-Hong; Salloway, Stephen; Danek, Adrian; Goate, Alison; Schofield, Peter R; Bateman, Randall J; Ewers, Michael

    2018-01-01

    Abstract Patients with Alzheimer’s disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer’s pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer’s disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer’s disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer’s disease, 55 controls from the Dominantly Inherited Alzheimer’s Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer’s disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer’s disease and cerebrospinal fluid tau levels in sporadic Alzheimer’s disease cases. In both autosomal dominant and sporadic Alzheimer’s disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer’s disease, a significant left frontal cortex connectivity

  19. A Risk Prediction Model for Sporadic CRC Based on Routine Lab Results.

    Science.gov (United States)

    Boursi, Ben; Mamtani, Ronac; Hwang, Wei-Ting; Haynes, Kevin; Yang, Yu-Xiao

    2016-07-01

    Current risk scores for colorectal cancer (CRC) are based on demographic and behavioral factors and have limited predictive values. To develop a novel risk prediction model for sporadic CRC using clinical and laboratory data in electronic medical records. We conducted a nested case-control study in a UK primary care database. Cases included those with a diagnostic code of CRC, aged 50-85. Each case was matched with four controls using incidence density sampling. CRC predictors were examined using univariate conditional logistic regression. Variables with p value CRC prediction models which included age, sex, height, obesity, ever smoking, alcohol dependence, and previous screening colonoscopy had an AUC of 0.58 (0.57-0.59) with poor goodness of fit. A laboratory-based model including hematocrit, MCV, lymphocytes, and neutrophil-lymphocyte ratio (NLR) had an AUC of 0.76 (0.76-0.77) and a McFadden's R2 of 0.21 with a NRI of 47.6 %. A combined model including sex, hemoglobin, MCV, white blood cells, platelets, NLR, and oral hypoglycemic use had an AUC of 0.80 (0.79-0.81) with a McFadden's R2 of 0.27 and a NRI of 60.7 %. Similar results were shown in an internal validation set. A laboratory-based risk model had good predictive power for sporadic CRC risk.

  20. Interaction between lifestyle factors and the XRCC1, XPD, and XRCC3 genetic variations modulates the risk for sporadic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Procopciuc Lucia Maria

    2014-03-01

    Full Text Available Introducere: Variațiile genetice, cum ar fi cele care influențează sistemele de reparare a defectelor de replicare a ADN, pot reprezenta factori de susceptibilitate în cancerul colorectal sporadic (CCR ca urmare a interacțiunii cu factori de mediu. Material și metodă: 80 de femei și 70 de bărbați, pacienți diagnosticați cu CCR sporadic în Clinica Chirurgie III Cluj au fost genotipați pentru Arg399Gln-XRCC1, Lys751Gln-XPD și Met241Thr-XRCC3 utilizând metodele PCR-RFLP. Am determinat de asemenea, genotipurile pentru 100 femei și 62 bărbați , care au format grupul de control. Rezultatele au fost analizate din punct de vedere al relației cu factorii de risc de mediu, fumatul și dieta. Rezultate: Bărbații fumători purtători ai variațiilor genetice Arg399Gln, Lys751Gln, Met241Thr au avut un risc semnificativ crescut de 4.09 (95%IC[0.96-19.98],p=0.05, 5.95(95%IC[1.08-43.22],p=0.03 și respectiv 3.73(95%IC[0.86-18.53],p=0.05 de a dezvolta cancer colorectal sporadic. Un risc semnificativ crescut de a dezvolta cancer colorectal sporadic a fost observat în cazul femeilor și bărbaților cu o dietă bogată în carne roșie prăjită purtători ai variațiilor genetice Arg399Gln (OR 2.77 95%IC [1.34-6.82],p=0.015 și OR 8.64 95%IC[2.67-29.14],p<0.001, Lys751Gln (OR 4.12 95%IC[1.37-12.74],p=0.007 și OR 5.06 95%IC[1.4- 19.02],p=0.006, Met241Thr (OR5.92 95%IC[2.21-16.23],p<0.001 și OR 5.64 95%IC[1.52-21.7],p=0.022. Femeile a căror dietă a inclus cantități mari de carne roșie prăjită au avut un risc semnificativ crescut de a dezvolta timpuriu cancer colorectal sporadic dacă au fost purtătoare a variațiilor genetice Arg399Gln-XRCC1 (OR 5.14 95%IC[0.99-28.3],p=0.047, Thr241Met-XRCC3 (OR 6.67 95%IC[1.05-46.67],p=0.025 și Lys751Gln-XPD (OR 4.7 95%IC[0.99-23.32],p=0.034. Concluzii: În cazul populației de origine română, asocierea genotipurilor mutante cu factori de mediu modulează riscul pentru CCR sporadic. La femei

  1. Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

    Science.gov (United States)

    Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

    2008-01-07

    To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

  2. Molecular genetic analysis of 103 sporadic colorectal tumours in Czech patients.

    Directory of Open Access Journals (Sweden)

    Peter Vasovcak

    Full Text Available The Czech Republic has one of the highest incidences of colorectal cancer (CRC in Europe. To evaluate whether sporadic CRCs in Czech patients have specific mutational profiles we analysed somatic genetic changes in known CRC genes (APC, KRAS, TP53, CTNNB1, MUTYH and BRAF, loss of heterozygosity (LOH at the APC locus, microsatellite instability (MSI, and methylation of the MLH1 promoter in 103 tumours from 102 individuals. The most frequently mutated gene was APC (68.9% of tumours, followed by KRAS (31.1%, TP53 (27.2%, BRAF (8.7% and CTNNB1 (1.9%. Heterozygous germline MUTYH mutations in 2 patients were unlikely to contribute to the development of their CRCs. LOH at the APC locus was found in 34.3% of tumours, MSI in 24.3% and MLH1 methylation in 12.7%. Seven tumours (6.9% were without any changes in the genes tested. The analysis yielded several findings possibly specific for the Czech cohort. Somatic APC mutations did not cluster in the mutation cluster region (MCR. Tumours with MSI but no MLH1 methylation showed earlier onset and more severe mutational profiles compared to MSI tumours with MLH1 methylation. TP53 mutations were predominantly located outside the hot spots, and transitions were underrepresented. Our analysis supports the observation that germline MUTYH mutations are rare in Czech individuals with sporadic CRCs. Our findings suggest the influence of specific ethnic genetic factors and/or lifestyle and dietary habits typical for the Czech population on the development of these cancers.

  3. Sporadic radio emission connected with a definite manifestation of solar activity in the near Earth space

    Science.gov (United States)

    Dudnic, A. V.; Zaljubovski, I. I.; Kartashev, V. M.; Shmatko, E. S.

    1985-01-01

    Sporadic radio emission of near Earth space at the frequency of 38 MHz is shown to appear in the event of a rapid development of instabilities in the ionospheric plasma. The instabilities are generated due to primary ionospheric disturbances occurring under the influence of solar chromospheric flares.

  4. A two-population sporadic meteoroid bulk density distribution and its implications for environment models

    Science.gov (United States)

    Moorhead, Althea V.; Blaauw, Rhiannon C.; Moser, Danielle E.; Campbell-Brown, Margaret D.; Brown, Peter G.; Cooke, William J.

    2017-12-01

    The bulk density of a meteoroid affects its dynamics in space, its ablation in the atmosphere, and the damage it does to spacecraft and lunar or planetary surfaces. Meteoroid bulk densities are also notoriously difficult to measure, and we are typically forced to assume a density or attempt to measure it via a proxy. In this paper, we construct a density distribution for sporadic meteoroids based on existing density measurements. We considered two possible proxies for density: the KB parameter introduced by Ceplecha and Tisserand parameter, TJ. Although KB is frequently cited as a proxy for meteoroid material properties, we find that it is poorly correlated with ablation-model-derived densities. We therefore follow the example of Kikwaya et al. in associating density with the Tisserand parameter. We fit two density distributions to meteoroids originating from Halley-type comets (TJ 2); the resulting two-population density distribution is the most detailed sporadic meteoroid density distribution justified by the available data. Finally, we discuss the implications for meteoroid environment models and spacecraft risk assessments. We find that correcting for density increases the fraction of meteoroid-induced spacecraft damage produced by the helion/antihelion source.

  5. Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.

    Science.gov (United States)

    Hook, Paul W; McClymont, Sarah A; Cannon, Gabrielle H; Law, William D; Morton, A Jennifer; Goff, Loyal A; McCallion, Andrew S

    2018-03-01

    Genetic variation modulating risk of sporadic Parkinson disease (PD) has been primarily explored through genome-wide association studies (GWASs). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal time points. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including genes with known PD associations and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1-null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Copyright © 2018 American Society of Human Genetics. All rights reserved.

  6. Synchronous GISTs associated with multiple sporadic tumors: a case report

    Directory of Open Access Journals (Sweden)

    Danila Comandini

    2017-08-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are rare neoplasms, but they also represent the most common mesenchymal tumors of the gastrointestinal tract originating from the cell of Cajal. GIST incidence ranges around 1% of all gastrointestinal malignancies. Approximately 5% of all GISTs have a hereditary etiology. The remaining 95% of GISTs are considered sporadic events, with up to 75% of cases driven by a constitutional activation of the c-KIT proto-oncogene. GISTs are generally solitary lesions. Nonetheless, multiple sporadic GISTs can occur and present as synchronous or metachronous tumors, usually associated with familial GIST. Here, we report a case of primary prostate and lung tumors associated with gastric and small bowel GISTs, unrelated to any known hereditary syndrome. Also, in the case we describe, the prostatic tumor came before the GISTs, while the lung tumor occurred later in time and led to pulmonary lobectomy plus lymphoadenectomy, with a diagnosis of nonsmall cell lung cancer. With the exception of a slight difference in lymphoid infiltration, the abdominal and gastric GIST nodules shared the same proliferative MIB1 index and mitotic count. However, the genetic analysis revealed that the gastric GIST and abdominal tumors were characterized by two different c-KIT mutations. This molecular heterogeneity supported the hypothesis of two different synchronous GISTs arising from stomach and ileum. At present, the patient is disease free and has already completed the third year of adjuvant therapy with imatinib. This case supports the importance of the analysis of c-KIT mutational status to distinguish metastases from synchronous multicentric GISTs, with relevant implications in therapeutic decisions, as well as the importance of a dedicated multidisciplinary team and of a radiological follow-up after the diagnosis of a primary GIST, to discover a relapse of the GIST or, possibly, additional malignancies.

  7. MicroRNAs discriminate familial from sporadic non-BRCA1/2 breast carcinoma arising in patients ≤35 years.

    Directory of Open Access Journals (Sweden)

    Elen Pereira Bastos

    Full Text Available The influence of genetic factors may contribute to the poor prognosis of breast cancer (BC at a very young age. However BRCA1/2 mutations could not explain the majority of cases arising in these patients. MicroRNAs (miRs have been implicated in biological processes associated with BC. Therefore, we investigated differences in miRs expression between tumors from young patients (≤35 years with sporadic or familial history and non-carriers of BRCA1/2 mutations. Thirty-six young Brazilian patients were divided into 2 groups: sporadic (NF-BC or familial breast cancer (F-BC. Most of the samples were classified as luminal A and B and the frequency of subtypes did not differ between familial or sporadic cases. Using real time qPCR and discriminant function analysis, we identified 9 miRs whose expression levels rather than miR identity can discriminate between both patient groups. Candidate predicted targets were determined by combining results from miRWalk algorithms with mRNA expression profiles (n = 91 differently expressed genes. MiR/mRNA integrated analysis identified 91 candidate genes showing positive or negative correlation to at least 1 of the 9 miRs. Co-expression analysis of these genes with 9 miRs indicated that 49 differentially co-expressed miR-gene interactions changes in F-BC tumors as compared to those of NF-BC tumors. Out of 49, 17 (34.6% of predicted miR-gene interactions showed an inverse correlation suggesting that miRs act as post-transcriptional regulators, whereas 14 (28.6% miR-gene pairs tended to be co-expressed in the same direction indicating that the effects exerted by these miRs pointed to a complex level of target regulation. The remaining 18 pairs were not predicted by our criteria suggesting involvement of other regulators. MiR-mRNA co-expression analysis allowed us to identify changes in the miR-mRNA regulation that were able to distinguish tumors from familial and sporadic young BC patients non-carriers of BRCA

  8. Gastric Medullary Carcinoma with Sporadic Mismatch Repair Deficiency and a TP53 R273C Mutation: An Unusual Case with Wild-Type BRAF

    Directory of Open Access Journals (Sweden)

    Brett M. Lowenthal

    2017-01-01

    Full Text Available Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1 and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

  9. Relationship between blood harmane and harmine concentrations in familial essential tremor, sporadic essential tremor and controls.

    Science.gov (United States)

    Louis, Elan D; Jiang, Wendy; Gerbin, Marina; Mullaney, Mary M; Zheng, Wei

    2010-12-01

    Harmane, a potent tremor-producing β-carboline alkaloid, may play a role in the etiology of essential tremor (ET). Blood harmane concentrations are elevated in ET cases compared with controls yet the basis for this elevation remains unknown. Decreased metabolic conversion (harmane to harmine) is one possible explanation. Using a sample of >500 individuals, we hypothesized that defective metabolic conversion of harmane to harmine might underlie the observed elevated harmane concentration in ET, and therefore expected to find a higher harmane to harmine ratio in familial ET than in sporadic ET or controls. Blood harmane and harmine concentrations were quantified by high performance liquid chromatography. There were 78 familial ET cases, 187 sporadic ET cases, and 276 controls. Blood harmane and harmine concentrations were correlated with one another (Spearman's r=0.24, p<0.001). The mean (±SD) harmane/harmine ratio=23.4±90.9 (range=0.1-987.5). The harmane/harmine ratio was highest in familial ET (46.7±140.4), intermediate in sporadic ET (28.3±108.1), and lowest in controls (13.5±50.3) (p=0.03). In familial ET cases, there was no association between this ratio and tremor severity (Spearman's r=0.08, p=0.48) or tremor duration (Spearman's r=0.14, p=0.24). The basis for the elevated blood harmane concentration, particularly in familial ET, is not known, although the current findings (highest harmane/harmine ratio in familial ET cases) lends support to the possibility that it could be the result of a genetically-driven reduction in harmane metabolism. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Blood-flow restricted resistance training in patients with sporadic inclusion body myositis

    DEFF Research Database (Denmark)

    Jørgensen, A.; Aagaard, P.; Frandsen, U.

    2018-01-01

    Objectives: To investigate the effect of 12 weeks of low-load blood-flow restricted resistance (BFR) training on self-reported and objective physical function, and maximal muscle strength in patients with sporadic inclusion body myositis (sIBM). Method: Twenty-two patients with sIBM were randomized......), which was used to measure self-reported physical function. All patients performed physical function tests (2-Minute Walk Test, Timed Up and Go, and 30-Second Chair Stand), completed the Inclusion Body Myositis Functional Rating Scale (IBMFRS), and were tested for isolated knee extensor muscle strength...

  11. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  12. Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.

    Science.gov (United States)

    Yamada, Rin; Yamaguchi, Tatsuro; Iijima, Takeru; Wakaume, Rika; Takao, Misato; Koizumi, Koichi; Hishima, Tsunekazu; Horiguchi, Shin-Ichiro

    2018-06-01

    The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55-37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50-45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

  13. Seizures in E200K familial and sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Appel, S; Chapman, J; Cohen, O S; Rosenmann, H; Nitsan, Z; Blatt, I

    2015-03-01

    Although seizures (other than myoclonus) are frequently reported in Creutzfeldt-Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown. To characterize the frequency of seizures in E200K familial and sporadic CJD, to describe its semiology, EEG and MRI findings. In this retrospective study, we reviewed all patients with CJD who were seen in the Sheba Medical Center between the years 2003-2012 and underwent clinical evaluation, genetic testing, EEG and MRI studies. The diagnosis of seizures was carried out based on documentation of episodes consistent with seizures or episode of unresponsiveness correlated with ictal activity in EEG. Sixty-four probable patients with CJD were included in the study, 57 (89%) with E200K familial (fCJD) and 7 (11%) with sporadic (sCJD). Seizures occurred in 8 patients: 3 of 7 (43%) in patients with sCJD compared to 5/57 (9%) in patients with E200K fCJD (P = 0.04, chi-square test). Two of E200K fCJD patients with seizures had other non-prion etiologies for seizures (brain metastasis, known history of temporal lobe epilepsy which started 44 years before the diagnosis of CJD). Seizures occurred late in the course of the disease with an average of 12 days between the onset of seizures and death. Seizures in E200K fCJD were infrequent and occurred late in the disease course. This difference suggests that E200K fCJD represents a separate subtype of the disease with distinct clinical characteristics. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD

    Directory of Open Access Journals (Sweden)

    Jeong Byung-Hoon

    2011-08-01

    Full Text Available Abstract Background Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s modulating susceptibility to prion disease. Ribosomal protein SA (RPSA, also called 37 kDa laminin receptor precursor (LRP/67 kDa laminin receptor (LR, acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR. Methods To identify other susceptibility genes involved in prion disease, we performed genetic analysis of RPSA. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on RPSA by direct sequencing or restriction fragment length polymorphism (RFLP analysis. Results We observed four single nucleotide polymorphisms (SNPs, including -8T>C (rs1803893 in the 5'-untranslated region (UTR of exon 2, 134-32C>T (rs3772138 in the intron, 519G>A (rs2269350 in the intron and 793+58C>T (rs2723 in the intron on the RPSA. The 519G>A (at codon 173 is located in the direct PrP binding site. The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients. Conclusion These results suggest that these RPSA polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of RPSA gene with sporadic CJD.

  15. Frequency of the LRRK2 G2019S mutation in late-onset sporadic patients with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Hsin Fen Chien

    2014-05-01

    Full Text Available Mutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson’s disease (PD. The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients. Method: We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR. Results: No G2019S mutations were found in both patients with sporadic PD and controls. Conclusions: Our results may be explained by the relatively small sample size.

  16. Sporadic Retinoblastoma and Parental Smoking and Alcohol Consumption before and after Conception: A Report from the Children's Oncology Group.

    Directory of Open Access Journals (Sweden)

    Saeedeh Azary

    Full Text Available Retinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception contribute to the two phenotypes (bilateral or unilateral of sporadic retinoblastoma.Two large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children's Oncology Group. Controls (n = 424 were selected from among friends and relatives of cases and matched by age. Risk factor information was obtained via telephone interview. We employed multivariable logistic regression to estimate the effects of parental tobacco smoking and alcohol consumption on retinoblastoma.Maternal smoking before and during pregnancy contributed to unilateral retinoblastoma risk in the child: year before pregnancy conditional Odds Ratio (OR, 8.9; 95% confidence interval (CI 1.5-51, and unconditional OR, 2.4; 95% CI, 1.3-4.7; month before or during pregnancy, conditional OR, 3.3; 95% CI, 0.5-20.8, and unconditional OR, 2.8; 95% CI, 1.1-7.0. No association was found for maternal or paternal alcohol consumption.The results of this study indicate that maternal active smoking during pregnancy may be a risk factor for sporadic retinoblastoma. Our study supports a role for tobacco exposures in embryonal tumors.

  17. Environmental risk factors for sporadic acoustic neuroma (Interphone Study Group, Germany)

    DEFF Research Database (Denmark)

    Schlehofer, B; Schlaefer, K; Blettner, M

    2007-01-01

    The only known risk factor for sporadic acoustic neuroma is high-dose ionising radiation. Environmental exposures, such as radiofrequency electromagnetic fields and noise are under discussion, as well as an association with allergic diseases. We performed a population-based case-control study.......31; 95% CI 1.15-4.66), and for hay fever (OR=2.20; 95% CI 1.09-4.45), but not for ionising radiation (OR=0.91; 95 % CI 0.51-1.61) or regular mobile phone use (OR=0.67; 95% CI 0.38-1.19). The study confirms results of recently published studies, although the pathogenetic mechanisms are still unknown....

  18. Inactivation of the Tumor Suppressor Genes Causing the Hereditary Syndromes Predisposing to Head and Neck Cancer via Promoter Hypermethylation in Sporadic Head and Neck Cancers

    OpenAIRE

    Smith, Ian M.; Mithani, Suhail K.; Mydlarz, Wojciech K.; Chang, Steven S.; Califano, Joseph A.

    2010-01-01

    Fanconi anemia (FA) and dyskeratosis congenita (DC) are rare inherited syndromes that cause head and neck squamous cell cancer (HNSCC). Prior studies of inherited forms of cancer have been extremely important in elucidating tumor suppressor genes inactivated in sporadic tumors. Here, we studied whether sporadic tumors have epigenetic silencing of the genes causing the inherited forms of HNSCC. Using bisulfite sequencing, we investigated the incidence of promoter hypermethylation of the 17 Fan...

  19. Common volume coherent and incoherent scatter radar observations of mid-latitude sporadic E-layers and QP echoes

    Directory of Open Access Journals (Sweden)

    D. L. Hysell

    2004-09-01

    Full Text Available Common-volume observations of sporadic E-layers made on 14-15 June 2002 with the Arecibo incoherent scatter radar and a 30MHz coherent scatter radar imager located on St. Croix are described. Operating in dual-beam mode, the Arecibo radar detected a slowly descending sporadic E-layer accompanied by a series of dense E-region plasma clouds at a time when the coherent scatter radar was detecting quasi-periodic (QP echoes. Using coherent radar imaging, we collocate the sources of the coherent scatter with the plasma clouds observed by Arecibo. In addition to patchy, polarized scattering regions drifting through the radar illuminated volume, which have been observed in previous imaging experiments, the 30MHz radar also detected large-scale electrostatic waves in the E-region over Puerto Rico, with a wavelength of about 30km and a period of about 10min, propagating to the southwest. Both the intensity and the Doppler shifts of the coherent echoes were modulated by the wave.

  20. Epidemiologic analysis of sporadic Salmonella typhi isolates and those from outbreaks by pulsed-field gel electrophoresis.

    Science.gov (United States)

    Thong, K L; Cheong, Y M; Puthucheary, S; Koh, C L; Pang, T

    1994-05-01

    Pulsed-field gel electrophoresis (PFGE) was used to compare and analyze 158 isolates of Salmonella typhi from five well-defined outbreaks of typhoid fever in Malaysia and also isolates involved in sporadic cases of typhoid fever occurring during the same period. Digestion of chromosomal DNAs from these S. typhi isolates with the restriction endonucleases XbaI (5'-TCTAGA-3'), SpeI (5'-ACTAGT-3'), and AvrII (5'-CCTAGG-3') and then PFGE produced restriction endonuclease analysis (REA) patterns consisting of 11 to 24 DNA fragments ranging in size from 20 to 630 kbp. Analysis of the REA patterns generated by PFGE after digestion with XbaI and SpeI indicated that the S. typhi isolates obtained from sporadic cases of infection were much more heterogeneous (at least 13 different REA patterns were detected; Dice coefficient, between 0.73 and 1.0) than those obtained during outbreaks of typhoid fever. The clonal nature and the close genetic identities of isolates from outbreaks in Alor Setar, Penang, Kota Kinabalu, Johor Bahru, and Kota Bahru were suggested by the fact that only a limited number of REA patterns, which mostly differed by only a single band, were detected (one to four patterns; Dice coefficient, between 0.82 and 1.0), although a different pattern was associated with each of these outbreaks. Comparison of REA patterns with ribotyping for 18 S. typhi isolates involved in sporadic cases of infection showed a good correlation, in that 72% of the isolates were in the same group. There was no clear correlation of phage types with a specific REA pattern. We conclude that PFGE of s. typhi chromosomal DNA digested with infrequently cutting restriction endonucleases is a useful method for comparing and differentiating S. typhi isolates for epidemiological purposes.

  1. Identification of chromosome aberrations in sporadic microsatellite stable and unstable colorectal cancers using array comparative genomic hybridization

    DEFF Research Database (Denmark)

    Jensen, Thomas Dyrsø; Li, Jian; Wang, Kai

    2011-01-01

    cancers constitute approximately 85% of sporadic cases, whereas microsatellite unstable (MSI) cases constitute the remaining 15%. In this study, we used array comparative genomic hybridization (aCGH) to identify genomic hotspot regions that harbor recurrent copy number changes. The study material...

  2. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

    Directory of Open Access Journals (Sweden)

    Mafalda Costa Neves

    2015-01-01

    Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

  3. Spatial distribution of West Nile virus in humans and mosquitoes in Israel, 2000-2014.

    Science.gov (United States)

    Lustig, Yaniv; Kaufman, Zalman; Mendelson, Ella; Orshan, Laor; Anis, Emilia; Glazer, Yael; Cohen, Daniel; Shohat, Tamy; Bassal, Ravit

    2017-11-01

    Israel has a long history of West Nile virus (WNV) morbidity, and the rate of detection of WNV in mosquitoes has been high since 2000. The aim of this study was to integrate several WNV datasets in order to gain an insight into the geographical distribution of WNV in Israel. Three choropleth maps were generated showing WNV human morbidity, WNV prevalence in mosquitoes, and the results of a nationwide serological survey, based on the division of Israel into 15 sub-districts. The maps show a high endemicity of WNV in Israel. In respect to the morbidity map, the population residing in the central part of the country and in Arava Region is at higher risk of developing the disease than the population of the rest of Israel. Interestingly, high prevalence rates of both WNV serology and WNV-infected mosquitoes were detected in Arava Region, but lower prevalence rates were detected in most areas of the coastal region, suggesting that other factors might also be important in the development of symptomatic WNV infections. These results underline the high prevalence of WNV in Israel and point to specific risk areas for WNV infections across the country. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Does reservoir host mortality enhance transmission of West Nile virus?

    Directory of Open Access Journals (Sweden)

    Foppa Ivo M

    2007-05-01

    Full Text Available Abstract Background Since its 1999 emergence in New York City, West Nile virus (WNV has become the most important and widespread cause of mosquito-transmitted disease in North America. Its sweeping spread from the Atlantic to the Pacific coast was accompanied by widespread mortality among wild birds, especially corvids. Only sporadic avian mortality had previously been associated with this infection in the Old World. Here, we examine the possibility that reservoir host mortality may intensify transmission, both by concentrating vector mosquitoes on remaining hosts and by preventing the accumulation of "herd immunity". Results Inspection of the Ross-Macdonald expression of the basic reproductive number (R0 suggests that this quantity may increase with reservoir host mortality. Computer simulation confirms this finding and indicates that the level of virulence is positively associated with the numbers of infectious mosquitoes by the end of the epizootic. The presence of reservoir incompetent hosts in even moderate numbers largely eliminated the transmission-enhancing effect of host mortality. Local host die-off may prevent mosquitoes to "waste" infectious blood meals on immune host and may thus facilitate perpetuation and spread of transmission. Conclusion Under certain conditions, host mortality may enhance transmission of WNV and similarly maintained arboviruses and thus facilitate their emergence and spread. The validity of the assumptions upon which this argument is built need to be empirically examined.

  5. Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Luigi Laghi

    Full Text Available Pancreatic cancer risk is increased in Lynch syndrome (LS patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI. However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.MS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27 in 338 consecutive pancreatic ductal adenocarcinoma (PDAC, resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.Only one PDAC (0.3% showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5% LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.MSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.

  6. Familial or Sporadic Idiopathic Scoliosis – classification based on artificial neural network and GAPDH and ACTB transcription profile

    Science.gov (United States)

    2013-01-01

    Background Importance of hereditary factors in the etiology of Idiopathic Scoliosis is widely accepted. In clinical practice some of the IS patients present with positive familial history of the deformity and some do not. Traditionally about 90% of patients have been considered as sporadic cases without familial recurrence. However the exact proportion of Familial and Sporadic Idiopathic Scoliosis is still unknown. Housekeeping genes encode proteins that are usually essential for the maintenance of basic cellular functions. ACTB and GAPDH are two housekeeping genes encoding respectively a cytoskeletal protein β-actin, and glyceraldehyde-3-phosphate dehydrogenase, an enzyme of glycolysis. Although their expression levels can fluctuate between different tissues and persons, human housekeeping genes seem to exhibit a preserved tissue-wide expression ranking order. It was hypothesized that expression ranking order of two representative housekeeping genes ACTB and GAPDH might be disturbed in the tissues of patients with Familial Idiopathic Scoliosis (with positive family history of idiopathic scoliosis) opposed to the patients with no family members affected (Sporadic Idiopathic Scoliosis). An artificial neural network (ANN) was developed that could serve to differentiate between familial and sporadic cases of idiopathic scoliosis based on the expression levels of ACTB and GAPDH in different tissues of scoliotic patients. The aim of the study was to investigate whether the expression levels of ACTB and GAPDH in different tissues of idiopathic scoliosis patients could be used as a source of data for specially developed artificial neural network in order to predict the positive family history of index patient. Results The comparison of developed models showed, that the most satisfactory classification accuracy was achieved for ANN model with 18 nodes in the first hidden layer and 16 nodes in the second hidden layer. The classification accuracy for positive Idiopathic

  7. Susceptibility and antibody response of Vesper Sparrows (Pooecetes gramineus) to West Nile virus: A potential amplification host in sagebrush-grassland habitat

    Science.gov (United States)

    Hofmeister, Erik K.; Dusek, Robert J.; Fassbinder-Orth, Carol; Owen, Benjamin; Franson, J. Christian

    2016-01-01

    West Nile virus (WNV) spread to the US western plains states in 2003, when a significant mortality event attributed to WNV occurred in Greater Sage-grouse ( Centrocercus urophasianus ). The role of avian species inhabiting sagebrush in the amplification of WNV in arid and semiarid regions of the North America is unknown. We conducted an experimental WNV challenge study in Vesper Sparrows ( Pooecetes gramineus ), a species common to sagebrush and grassland habitats found throughout much of North America. We found Vesper Sparrows to be moderately susceptible to WNV, developing viremia considered sufficient to transmit WNV to feeding mosquitoes, but the majority of birds were capable of surviving infection and developing a humoral immune response to the WNV nonstructural 1 and envelope proteins. Despite clearance of viremia, after 6 mo, WNV was detected molecularly in three birds and cultured from one bird. Surviving Vesper Sparrows were resistant to reinfection 6 mo after the initial challenge. Vesper sparrows could play a role in the amplification of WNV in sagebrush habitat and other areas of their range, but rapid clearance of WNV may limit their importance as competent amplification hosts of WNV.

  8. Predictors of Preoperative Tinnitus in Unilateral Sporadic Vestibular Schwannoma

    Directory of Open Access Journals (Sweden)

    Georgios Naros

    2017-08-01

    Full Text Available ObjectiveNearly two-thirds of patients with vestibular schwannoma (VS are reporting a significantly impaired quality of life due to tinnitus. VS-associated tinnitus is attributed to an anatomical and physiological damage of the hearing nerve by displacing growth of the tumor. In contrast, the current pathophysiological concept of non-VS tinnitus hypothesizes a maladaptive neuroplasticity of the central nervous system to a (hidden hearing impairment resulting in a subjective misperception. However, it is unclear whether this concept fits to VS-associated tinnitus. This study aims to determine the clinical predictors of VS-associated tinnitus to ascertain the compatibility of both pathophysiological concepts.MethodsThis retrospective study includes a group of 478 neurosurgical patients with unilateral sporadic VS evaluated preoperatively regarding the occurrence of ipsilateral tinnitus depending on different clinical factors, i.e., age, gender, tumor side, tumor size (T1–T4 according to the Hannover classification, and hearing impairment (Gardner–Robertson classification, GR1–5, using a binary logistic regression.Results61.8% of patients complain about a preoperative tinnitus. The binary logistic regression analysis identified male gender [OR 1.90 (1.25–2.75; p = 0.002] and hearing impairment GR3 [OR 1.90 (1.08–3.35; p = 0.026] and GR4 [OR 8.21 (2.29–29.50; p = 0.001] as positive predictors. In contrast, patients with large T4 tumors [OR 0.33 (0.13–0.86; p = 0.024] and complete hearing loss GR5 [OR 0.36 (0.15–0.84; p = 0.017] were less likely to develop a tinnitus. Yet, 60% of the patients with good clinical hearing (GR1 and 25% of patients with complete hearing loss (GR5 suffered from tinnitus.ConclusionThese data are good accordance with literature about non-VS tinnitus indicating hearing impairment as main risk factor. In contrast, complete hearing loss appears a negative predictor for tinnitus. For the first

  9. Identification of novel missense mutations in the Norrie disease gene associated with one X-linked and four sporadic cases of familial exudative vitreoretinopathy.

    Science.gov (United States)

    Shastry, B S; Hejtmancik, J F; Trese, M T

    1997-01-01

    X-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye disorder that affects both the retina and the vitreous body. It is characterized by an abnormal vascularization of the peripheral retina. It has been previously shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are allelic. In this report we describe four novel mutations (R41K, H42R, K58N, and Y120C) in the Norrie disease gene associated with one X-linked and four sporadic cases of FEVR. One mutation (H42R) was found to be segregating with the disease in three generations (X-linked family), and the others are sporadic. These sequence alterations changed the encoded amino acids in the Norrie disease protein and were not found in 17 unaffected family members or in 36 randomly selected normal individuals. This study provides additional evidence that mutations in the same gene can result in FEVR and Norrie disease. It also demonstrates that it may be beneficial for clinical diagnosis to screen for mutations in the Norrie disease gene in sporadic FEVR cases.

  10. West Nile virus blood transfusion-related infection despite nucleic acid testing.

    Science.gov (United States)

    Macedo de Oliveira, Alexandre; Beecham, Brady D; Montgomery, Susan P; Lanciotti, Robert S; Linnen, Jeffrey M; Giachetti, Cristina; Pietrelli, Larry A; Stramer, Susan L; Safranek, Thomas J

    2004-12-01

    A case of West Nile virus (WNV) encephalitis associated with transfusion of blood that did not react when tested for WNV by minipool (MP) nucleic acid testing (NAT) is described. A Nebraska man developed clinical encephalitis 13 days after surgery and transfusion of 26 blood components. Antibody testing confirmed WNV infection. An investigation was initiated to determine the source of this infection. The patient's family members were interviewed to identify risk factors for WNV infection. Residual samples were retested for WNV RNA using transcription-mediated amplification (TMA) assay and two polymerase chain reaction (PCR) assays. Blood donors' follow-up serum samples were collected. All samples were tested for WNV-specific immunoglobulin M antibodies. The patient's family denied recent mosquito exposure. The 20 blood components collected after July 2003 did not react when tested for WNV in a six-member MP-NAT at the time of donation. Retrospective individual testing identified one sample as WNV-reactive by the TMA assay and one of the PCR assays. Seroconversion was demonstrated in the donor associated with this sample. WNV RNA detection by individual donation NAT demonstrates viremic blood escaping MP-NAT and supports transfusion-related WNV transmission. MP-NAT may not detect all WNV-infected blood donors, allowing WNV transmission to continue at low levels. WNV NAT assays might vary in sensitivity and pooling donations could further impact test performance. Understanding MP NAT limitations can improve strategies to maintain safety of the blood supply in the United States.

  11. Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects.

    Science.gov (United States)

    Daly, Adrian F; Yuan, Bo; Fina, Frederic; Caberg, Jean-Hubert; Trivellin, Giampaolo; Rostomyan, Liliya; de Herder, Wouter W; Naves, Luciana A; Metzger, Daniel; Cuny, Thomas; Rabl, Wolfgang; Shah, Nalini; Jaffrain-Rea, Marie-Lise; Zatelli, Maria Chiara; Faucz, Fabio R; Castermans, Emilie; Nanni-Metellus, Isabelle; Lodish, Maya; Muhammad, Ammar; Palmeira, Leonor; Potorac, Iulia; Mantovani, Giovanna; Neggers, Sebastian J; Klein, Marc; Barlier, Anne; Liu, Pengfei; Ouafik, L'Houcine; Bours, Vincent; Lupski, James R; Stratakis, Constantine A; Beckers, Albert

    2016-04-01

    Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101 We studied XLAG syndrome patients (n= 18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2ratio (LR) compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8%. These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR) technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. © 2016 Society for Endocrinology.

  12. Functional impairment in patients with sporadic Inclusion Body Myositis.

    Science.gov (United States)

    Dunlap, Heather V; Macneil, Lauren G; Tarnopolsky, Mark A

    2014-03-01

    We conducted a retrospective chart review of 53 patients diagnosed with sporadic Inclusion Body Myositis (sIBM) who have been followed at the McMaster Neuromuscular Clinic since 1996. We reviewed patient medical histories in order to compare our findings with similar cohorts, and analyzed quantitative strength data to determine functionality in guiding decisions related to gait assistive devices. Patient information was acquired through retrospective clinic chart review. Our study found knee extension strength decreased significantly as patients transitioned to using more supportive gait assistive devices (P cane)(P Falls and fear of falling poses a significant threat to patient physical well-being. The prevalence of dysphagia increased as patients required more supportive gait devices, and finally a significant negative correlation was found between time after onset and creatine kinase (CK) levels (P falling would be beneficial in preventing future falls and improving long-term patient outcomes.

  13. Transmission of West Nile virus by Culex quinquefasciatus say infected with Culex Flavivirus Izabal.

    Directory of Open Access Journals (Sweden)

    Rebekah J Kent

    Full Text Available BACKGROUND: The natural history and potential impact of mosquito-specific flaviviruses on the transmission efficiency of West Nile virus (WNV is unknown. The objective of this study was to determine whether or not prior infection with Culex flavivirus (CxFV Izabal altered the vector competence of Cx. quinquefasciatus Say for transmission of a co-circulating strain of West Nile virus (WNV from Guatemala. METHODS AND FINDINGS: CxFV-negative Culex quinquefasciatus and those infected with CxFV Izabal by intrathoracic inoculation were administered WNV-infectious blood meals. Infection, dissemination, and transmission of WNV were measured by plaque titration on Vero cells of individual mosquito bodies, legs, or saliva, respectively, two weeks following WNV exposure. Additional groups of Cx. quinquefasciatus were intrathoracically inoculated with WNV alone or WNV+CxFV Izabal simultaneously, and saliva collected nine days post inoculation. Growth of WNV in Aedes albopictus C6/36 cells or Cx. quinquefasciatus was not inhibited by prior infection with CxFV Izabal. There was no significant difference in the vector competence of Cx. quinquefasciatus for WNV between mosquitoes uninfected or infected with CxFV Izabal across multiple WNV blood meal titers and two colonies of Cx. quinquefasciatus (p>0.05. However, significantly more Cx. quinquefasciatus from Honduras that were co-inoculated simultaneously with both viruses transmitted WNV than those inoculated with WNV alone (p = 0.0014. Co-inoculated mosquitoes that transmitted WNV also contained CxFV in their saliva, whereas mosquitoes inoculated with CxFV alone did not contain virus in their saliva. CONCLUSIONS: In the sequential infection experiments, prior infection with CxFV Izabal had no significant impact on WNV replication, infection, dissemination, or transmission by Cx. quinquefasciatus, however WNV transmission was enhanced in the Honduras colony when mosquitoes were inoculated simultaneously with

  14. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma.

    Science.gov (United States)

    Bayley, Jean-Pierre; Kunst, Henricus P M; Cascon, Alberto; Sampietro, Maria Lourdes; Gaal, José; Korpershoek, Esther; Hinojar-Gutierrez, Adolfo; Timmers, Henri J L M; Hoefsloot, Lies H; Hermsen, Mario A; Suárez, Carlos; Hussain, A Karim; Vriends, Annette H J T; Hes, Frederik J; Jansen, Jeroen C; Tops, Carli M; Corssmit, Eleonora P; de Knijff, Peter; Lenders, Jacques W M; Cremers, Cor W R J; Devilee, Peter; Dinjens, Winand N M; de Krijger, Ronald R; Robledo, Mercedes

    2010-04-01

    Paragangliomas and phaeochromocytomas are neuroendocrine tumours associated frequently with germline mutations of SDHD, SDHC, and SDHB. Previous studies have shown the imprinted SDHAF2 gene to be mutated in a large Dutch kindred with paragangliomas. We aimed to identify SDHAF2 mutation carriers, assess the clinical genetic significance of SDHAF2, and describe the associated clinical phenotype. We undertook a multicentre study in Spain and The Netherlands in 443 apparently sporadic patients with paragangliomas and phaeochromocytomas who did not have mutations in SDHD, SDHC, or SDHB. We analysed DNA of 315 patients for germline mutations of SDHAF2; a subset (n=200) was investigated for gross gene deletions. DNA from a group of 128 tumours was studied for somatic mutations. We also examined a Spanish family with head and neck paragangliomas with a young age of onset for the presence of SDHAF2 mutations, undertook haplotype analysis in this kindred, and assessed their clinical phenotype. We did not identify any germline or somatic mutations of SDHAF2, and no gross gene deletions were noted in the subset of apparently sporadic patients analysed. Investigation of the Spanish family identified a pathogenic germline DNA mutation of SDHAF2, 232G-->A (Gly78Arg), identical to the Dutch kindred. SDHAF2 mutations do not have an important role in phaeochromocytoma and are rare in head and neck paraganglioma. Identification of a second family with the Gly78Arg mutation suggests that this is a crucial residue for the function of SDHAF2. We conclude that SDHAF2 mutation analysis is justified in very young patients with isolated head and neck paraganglioma without mutations in SDHD, SDHC, or SDHB, and in individuals with familial antecedents who are negative for mutations in all other risk genes. Dutch Cancer Society, European Union 6th Framework Program, Fondo Investigaciones Sanitarias, Fundación Mutua Madrileña, and Red Temática de Investigación Cooperativa en Cáncer. 2010

  15. PRKAG3 polymorphisms associated with sporadic Wolff-Parkinson-White syndrome among a Taiwanese population.

    Science.gov (United States)

    Weng, Ken-Pen; Yuh, Yeong-Seng; Huang, Shih-Hui; Hsiao, Hsiang-Chiang; Wu, Huang-Wei; Chien, Jen-Hung; Chen, Bo-Hau; Huang, Shih-Ming; Chien, Kuang-Jen; Ger, Luo-Ping

    2016-12-01

    The aim of this study was to investigate whether mutation in AMP-activated protein kinase (AMPK) subunit genes (PRKAG3-230) is associated with sporadic, isolated Wolff-Parkinson-White (WPW) syndrome. This study consisted of 87 patients with symptomatic WPW syndrome and 93 healthy controls. PRKAG3-230 genotypes were determined using real-time polymerase chain reaction assay. Genotype and allele frequencies of PRKAG3-230 between patients with WPW syndrome and healthy controls were ascertained using chi-square test or Fisher exact test when appropriate. PRKAG3-230 were genotyped in 87 patients (53 men and 34 women; age=24.4±18.0 years) with WPW syndrome and 93 healthy controls (57 men and 36 women; age=16.8±4.2 years). There were no significant differences between the two groups in terms of age and sex. The patients with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype [odds ratio (OR)=1.99, 95% confidence interval (CI)=1.01-3.89, p=0.045; OR=1.99, 95% CI=1.04-3.78, p=0.037, respectively]. The allelic types were not associated with the risk of WPW syndrome. The patients with manifest type with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype (OR=2.86, 95% CI=1.16-7.05, p=0.022; OR=2.84, 95% CI=1.19-6.80, p=0.019, respectively). The patients with right-side accessory pathways with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype (OR=3.07, 95% CI=1.25-7.51, p=0.014; OR=2.84, 95% CI=1.19-6.80, p=0.019, respectively). The allelic types were not associated with the risk of WPW types and locations. This study shows that PRKAG3-230 may be associated with sporadic WPW syndrome among a Taiwanese population. Further studies are warranted to elucidate the role of mutations in AMPK subunit genes other than PRKAG3-230 in sporadic WPW syndrome. Copyright © 2016. Published by Elsevier Taiwan LLC.

  16. Analysis of wave-like oscillations in parameters of sporadic E layer and neutral atmosphere

    Czech Academy of Sciences Publication Activity Database

    Mošna, Zbyšek; Koucká Knížová, Petra

    90-91, SI (2012), s. 172-178 ISSN 1364-6826. [IAGA/ICMA/CAWSES-II TG4 Workshop on Vertical Coupling in the Atmosphere-Ionosphere System /4./. Prague, 14.02.2011-18.02.2011] R&D Projects: GA AV ČR IAA300420704 Institutional support: RVO:68378289 Keywords : Sporadic E * Planetary waves * Tidal waves * Mid-latitude ionosphere Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.417, year: 2012 http://www.sciencedirect.com/science/article/pii/S1364682612001186

  17. Oral and parenteral immunization of chickens (Gallus gallus) against West Nile virus with recombinant envelope protein

    Science.gov (United States)

    Fassbinder-Orth, C. A.; Hofmeister, Erik K.; Weeks-Levy, C.; Karasov, W.H.

    2009-01-01

    West Nile virus (WNV) causes morbidity and mortality in humans, horses, and in more than 315 bird species in North America. Currently approved WNV vaccines are designed for parenteral administration and, as yet, no effective oral WNV vaccines have been developed. WNV envelope (E) protein is a highly antigenic protein that elicits the majority of virus-neutralizing antibodies during a WNV immune response. Leghorn chickens were given three vaccinations (each 2 wk apart) of E protein orally (20 ??g or 100 ??g/dose), of E protein intramuscularly (IM, 20 ??g/dose), or of adjuvant only (control group) followed by a WNV challenge. Viremias were measured post-WNV infection, and three new enzyme-linked immunosorbent assays were developed for quantifying IgM, IgY, and IgA-mediated immune response of birds following WNV infection. WNV viremia levels were significantly lower in the IM group than in both oral groups and the control group. Total WNV E protein-specific IgY production was significantly greater, and WNV nonstructural 1-specific IgY was significantly less, in the IM group compared to all other treatment groups. The results of this study indicate that IM vaccination of chickens with E protein is protective against WNV infection and results in a significantly different antibody production profile as compared to both orally vaccinated and nonvaccinated birds. ?? 2009 American Association of Avian Pathologists.

  18. West Nile virus outbreak in Israel in 2015: phylogenetic and geographic characterization in humans and mosquitoes.

    Science.gov (United States)

    Lustig, Y; Kaufman, Z; Mannasse, B; Koren, R; Katz-Likvornik, S; Orshan, L; Glatman-Freedman, A; Mendelson, E

    2017-12-01

    West Nile Virus (WNV) is endemic in Israel and was responsible for several outbreaks in the past 16 years. The aim of the present study was to investigate the spatial distribution of WNV acute infections from an outbreak that occurred in 2015 in Israel and report the molecular and geographic characterization of WNV isolates from human cases and mosquito pools obtained during this outbreak. Using a geographical layer comprising 51 continuous areas of Israel, the number of WNV infection cases per 100 000 people in each area and the locations of WNV-infected mosquitoes in 2015 were analysed. Sequencing and phylogenetic analyses followed by geographic localization were performed on 13 WNV human isolates and 19 WNV-infected mosquito pools. Substantial geographical variation in the prevalence of acute WNV in patients in Israel was found and an overall correlation with WNV-infected mosquitoes. All human patients sequenced were infected only with the Mediterranean subtype of WNV Lineage 1 and resided primarily in the coastal regions in central Israel. In contrast, mosquitoes were infected with both the Mediterranean and Eastern European subtypes of WNV lineage 1; however, only the Mediterranean subtype was found in mosquitoes from the coastal region in central Israel. These results demonstrate differential geographic dispersion in Israel of the two WNV subtypes and may also point to a differential pattern of human infections. As a geographical bridge between Europe, Asia and Africa, analysis of WNV circulation in humans and mosquitoes in Israel provides information relevant to WNV infections in Eurasia. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Positive 14-3-3 and tau proteins in a sporadic Creutzfeldt-Jakob disease case and a brief perspective of prion diseases in Colombia.

    Science.gov (United States)

    Escandón-Vargas, Kevin; Zorrilla-Vaca, Andrés; Corral-Prado, Raúl Heli

    2016-02-24

    Prion diseases are rare neurodegenerative disorders occurring worldwide and affecting both humans and animals. Herein, we present the case of a patient diagnosed with definite sporadic Creutzfeldt-Jakob disease in Cali, Colombia. Besides neurological examination, 14-3-3 and tau proteins were valuable tools supporting the diagnosis. We also present a brief perspective of the prion diseases reported in Colombia to date. Although the incidence of prion diseases is unknown in Colombia, our literature review revealed that one case of scrapie in 1981 and 29 human sporadic cases of Creutzfeldt-Jakob disease have been documented and published in our country.

  20. Epidemiological evaluation of sporadic cases of Norovirus infection in comunitary and hospitalized patients

    Directory of Open Access Journals (Sweden)

    Sara Giordana Rimoldi

    2009-03-01

    Full Text Available Surveillace of viral gastoenteritis infections is very poor in Italy, even if starting from 2004 Norovirus became one of the most causative agent of infections in all the seasons. The aim of our study was to evaluate the isolation of Norovirus both in hospitalizes patients and communitary patients. From October 2006 to March 2008 we examined 400 samples. Our results showed only 15 sporadic cases in pediatric, HIV comunitary patients. These cases were analyzed by using an ELISA screening (Biopharm and the results were confirmed with real time PCT (Argene.

  1. Relationships between infection, dissemination, and transmission of West Nile virus RNA in Culex pipiens quinquefasciatus (Diptera: Culicidae).

    Science.gov (United States)

    Richards, Stephanie L; Anderson, Sheri L; Lord, Cynthia C; Smartt, Chelsea T; Tabachnick, Walter J

    2012-01-01

    Culex pipiens quinquefasciatus Say fed blood containing 6.8 +/- 0.3 logs (mean +/- SE) plaque-forming units of West Nile virus (WNV)/ml were maintained at 28 degrees C for incubation periods (IP) of 7, 14, or 21 d. Several attributes of vector competence were determined at each IP using quantitative real-time reverse transcriptase polymerase chain reaction to estimate plaque forming unit equivalents including: infection rate (WNV-positive abdomens), dissemination rate (WNV-positive legs or thoraces), combined dissemination rate (WNV-positive legs and thoraces), transmission rate (WNV-positive saliva), and WNV titers in abdomens, legs, thoraces, and saliva. Each rate increased or was equivalent with increasing IP. Mosquitoes transmitting WNV in saliva also had significantly higher IP-dependent WNV titers in abdomens, legs, and thoraces. Titers of WNV in abdomens were significantly correlated with titers in legs and thoraces, but the degree of association changed with IP. However, titers of abdomens, legs, and thoraces were not correlated with WNV presence or titer in the saliva. The results show that WNV presence or titer in the saliva of infected Cx. p. quinquefasciatus was not directly influenced by processes involved in WNV replication in other tissues. The processes controlling midgut infection and escape are, in part, independent from the infection processes in other tissues. The relationship between infection, dissemination, and transmission varied over time. The infection and replication of WNV in different tissues is likely influenced by different barriers encountered during the extrinsic incubation period. The significance of these observations for understanding vector competence is discussed.

  2. Rainfall is a risk factor for sporadic cases of Legionella pneumophila pneumonia.

    Directory of Open Access Journals (Sweden)

    Carolina Garcia-Vidal

    Full Text Available It is not known whether rainfall increases the risk of sporadic cases of Legionella pneumonia. We sought to test this hypothesis in a prospective observational cohort study of non-immunosuppressed adults hospitalized for community-acquired pneumonia (1995-2011. Cases with Legionella pneumonia were compared with those with non-Legionella pneumonia. Using daily rainfall data obtained from the regional meteorological service we examined patterns of rainfall over the days prior to admission in each study group. Of 4168 patients, 231 (5.5% had Legionella pneumonia. The diagnosis was based on one or more of the following: sputum (41 cases, antigenuria (206 and serology (98. Daily rainfall average was 0.556 liters/m(2 in the Legionella pneumonia group vs. 0.328 liters/m(2 for non-Legionella pneumonia cases (p = 0.04. A ROC curve was plotted to compare the incidence of Legionella pneumonia and the weighted median rainfall. The cut-off point was 0.42 (AUC 0.54. Patients who were admitted to hospital with a prior weighted median rainfall higher than 0.42 were more likely to have Legionella pneumonia (OR 1.35; 95% CI 1.02-1.78; p = .03. Spearman Rho correlations revealed a relationship between Legionella pneumonia and rainfall average during each two-week reporting period (0.14; p = 0.003. No relationship was found between rainfall average and non-Legionella pneumonia cases (-0.06; p = 0.24. As a conclusion, rainfall is a significant risk factor for sporadic Legionella pneumonia. Physicians should carefully consider Legionella pneumonia when selecting diagnostic tests and antimicrobial therapy for patients presenting with CAP after periods of rainfall.

  3. Sporadic frame dropping impact on quality perception

    Science.gov (United States)

    Pastrana-Vidal, Ricardo R.; Gicquel, Jean Charles; Colomes, Catherine; Cherifi, Hocine

    2004-06-01

    Over the past few years there has been an increasing interest in real time video services over packet networks. When considering quality, it is essential to quantify user perception of the received sequence. Severe motion discontinuities are one of the most common degradations in video streaming. The end-user perceives a jerky motion when the discontinuities are uniformly distributed over time and an instantaneous fluidity break is perceived when the motion loss is isolated or irregularly distributed. Bit rate adaptation techniques, transmission errors in the packet networks or restitution strategy could be the origin of this perceived jerkiness. In this paper we present a psychovisual experiment performed to quantify the effect of sporadically dropped pictures on the overall perceived quality. First, the perceptual detection thresholds of generated temporal discontinuities were measured. Then, the quality function was estimated in relation to a single frame dropping for different durations. Finally, a set of tests was performed to quantify the effect of several impairments distributed over time. We have found that the detection thresholds are content, duration and motion dependent. The assessment results show how quality is impaired by a single burst of dropped frames in a 10 sec sequence. The effect of several bursts of discarded frames, irregularly distributed over the time is also discussed.

  4. West Nile virus infection in American Robins: new insights on dose response.

    Directory of Open Access Journals (Sweden)

    Kaci K VanDalen

    Full Text Available West Nile virus (WNV is a vector-borne pathogen that was first detected in the United States in 1999. The natural transmission cycle of WNV involves mosquito vectors and avian hosts, which vary in their competency to transmit the virus. American robins are an abundant backyard species in the United States and appear to have an important role in the amplification and dissemination of WNV. In this study we examine the response of American robins to infection with various WNV doses within the range of those administered by some natural mosquito vectors. Thirty American robins were assigned a WNV dosage treatment and needle inoculated with 10(0.95 PFU, 10(1.26 PFU, 10(2.15 PFU, or 10(3.15 PFU. Serum samples were tested for the presence of infectious WNV and/or antibodies, while oral swabs were tested for the presence of WNV RNA. Five of the 30 (17% robins had neutralizing antibodies to WNV prior to the experiment and none developed viremia or shed WNV RNA. The proportion of WNV-seronegative birds that became viremic after WNV inoculation increased in a dose dependent manner. At the lowest dose, only 40% (2/5 of the inoculated birds developed productive infections while at the highest dose, 100% (7/7 of the birds became viremic. Oral shedding of WNV RNA followed a similar trend where robins inoculated with the lower two doses were less likely to shed viral RNA (25% than robins inoculated with one of the higher doses (92%. Viremia titers and morbidity did not increase in a dose dependent manner; only two birds succumbed to infection and, interestingly, both were inoculated with the lowest dose of WNV. It is clear that the disease ecology of WNV is a complex interplay of hosts, vectors, and viral dose delivered.

  5. Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer

    International Nuclear Information System (INIS)

    Cox, David G; Kraft, Peter; Hankinson, Susan E; Hunter, David J

    2005-01-01

    Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer. We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls). One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02–1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women. We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear

  6. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

    International Nuclear Information System (INIS)

    Kringen, Pedro; Wang, Yun; Dumeaux, Vanessa; Kristensen, Gunnar; Borresen-Dale, Anne-Lise; Dorum, Anne

    2005-01-01

    Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive. DNA was extracted from paraffin embedded formalin fixed tissues for the familial cases, and from fresh frozen specimen from the sporadic cases. All cases were treated at our hospital according to protocol. Mutation analyses of exon 2 – 11 were performed using TTGE, followed by sequencing. Survival rates for BRCA1-familial cases with TP53 mutations were not significantly lower than for familial cases without TP53 mutations (p = 0.25, RR = 1.64, 95% CI [0.71–3.78]). Median age at diagnosis for sporadic (59 years) and familial (49 years) cases differed significantly (p < 0.001) with or without TP53 mutations. Age at diagnosis between the two types of familial carriers were not significantly different, with median age of 47 for 1675delA and 52.5 for 1135insA carriers (p = 0.245). For cases ≥50 years at diagnosis, a trend toward longer survival for sporadic over familial cases was observed (p = 0.08). The opposite trend was observed for cases <50 years at diagnosis. There do not seem to be a protective advantage for familial BRCA1 carriers without TP53 mutations over familial cases with TP53 mutations. However, there seem to be a trend towards initial advantage in survival for familial cases compared to sporadic cases diagnosed before the age of 50 both with and without TP53 mutations. However, this trend diminishes over time and for cases diagnosed ≥50 years the sporadic cases show a trend towards an advantage in survival over familial cases. Although this data set is small, if confirmed, this may be a link in the evidence that the differences in ovarian cancer survival reported, are

  7. [Correlation anslysis of sporadic breast cancer and BRCA1 gene plymorphisms in the Han Nationality and the Mongol Nationality of Inner Mongolia Region].

    Science.gov (United States)

    Ma, Jinzhu; Liu, Ming; Zhang, Xinlai; BuRi, Gude

    2015-12-08

    To study the correlationship between the BRCA1 gene polymorphisms, especially in 2731 loci (rs799917), and sporadic breast cancer in the Han nationality and the Mongol nationality of the Inner Mongolia region. Using the prospective study method, 103 cases of patients with sporadic breast cancer (case group) and 103 cases of normal physical examination people (control group) were enrolled. PCR and direct sequencing method were used for analyzing the correlationship of 2731 loci polymorphisms of BRCA1 and sporadic breast cancer in our zone. In the case group, the age stratification, pathologic stage, immunohistochemistry and the distribution of lymph node metastasis had no significant difference in two ethnic group (P> 0.05). The age stratification of control group also had no significant difference in two ethnic group (P>0. 05). There was no statistically significant difference in age stratification of the case group and the control group (P>0.05). In the Inner Mongolia region, BRCA1 gene 2731 loci genotypes check out three genotypes: namely TT, CT and CC. The frequencies of genotype TT, CT, CC in the case group were 13.1%, 26.2%, 60.7% ( the Han nationality) and 16.7%, 28.6%, 54.7% (the Mongol nationality), respectively. Meanwhile the frequencies of allele T and allele C were 71.8% and 28.2%. In the control group, the frequencies of genotype TT, CT, CC were 18.0%, 31.1%, 50.9% ( the Han nationality) and 23.8%, 38.1%, 38.1% ( the Mongol nationality), respectively, and the frequencies of allele T and allele C were 62.9% and 37.1%. BRCA1 gene 2 731 loci gene polymorphism had no significant difference in two groups (χ(2)=3.438, P=0.752), but T allele frequency distribution in the case group was significantly increased (χ(2)=4.185, P=0.041). There is no obvious correlation between the BRCA1 gene 2731 loci and sporadic breast cancer in the Han nationality and the Mongol nationality of the Inner Mongolia region. C allele of BRCA1 gene 2731 loci may be one of the

  8. OUTPATIENT PHYSICAL THERAPY EVALUATION AND TREATMENT OF A PATIENT DIAGNOSED WITH SPORADIC INCLUSION BODY MYOSITIS: A CASE STUDY

    Directory of Open Access Journals (Sweden)

    Tyler Harrigfeld

    2017-08-01

    Full Text Available Background: Sporadic inclusion body myositis is an autoimmune and degenerative disorder of skeletal muscle that affects people at random. It most commonly begins as progressive weakness and atrophy of lower extremity musculature, beginning with the proximal leg. These impairments in body structure adversely affect the performance of functional activities and mobility, resulting in a progressive decrease in independence and participation both at home and in the community. Physical therapy attempts to minimize these effects through educational and procedural interventions focused on treating impairments and limitations. The purpose of this case study was to provide a description of the physical therapy management of a patient diagnosed with sporadic inclusion body myositis. Case Summary: The patient was a 66-year-old male who was diagnosed with sporadic inclusion body myositis with a chief complaint of weakness and fall risk. He presented with generalized lower extremity weakness and atrophy of bilateral quadriceps, as well as impaired balance and increasing fatigue with activity. Therapeutic exercise, home exercise program, balance, gait, and stair training were delivered to address these impairments. Patient outcomes showed improvement in balance and safety with functional activities. Discussion: The patient was seen for seven visits that were 45 – 60 minutes in length, over a five-week period. The patient made subjective reports of improvement in functional activities and balance; however many objective outcome measures could not be reassessed. There is a need for further research on this population to determine the effectiveness and parameters of physical therapy interventions. Conclusion: Physical therapy may have helped improve balance as well as subjective reports from the patient of increased feeling of confidence while navigating stairs.

  9. Sporadic inclusion body myositis: the genetic contributions to the pathogenesis

    Science.gov (United States)

    2014-01-01

    Sporadic inclusion body myositis (sIBM) is the commonest idiopathic inflammatory muscle disease in people over 50 years old. It is characterized by slowly progressive muscle weakness and atrophy, with typical pathological changes of inflammation, degeneration and mitochondrial abnormality in affected muscle fibres. The cause(s) of sIBM are still unknown, but are considered complex, with the contribution of multiple factors such as environmental triggers, ageing and genetic susceptibility. This review summarizes the current understanding of the genetic contributions to sIBM and provides some insights for future research in this mysterious disease with the advantage of the rapid development of advanced genetic technology. An international sIBM genetic study is ongoing and whole-exome sequencing will be applied in a large cohort of sIBM patients with the aim of unravelling important genetic risk factors for sIBM. PMID:24948216

  10. MicroRNA (miRNA Signaling in the Human CNS in Sporadic Alzheimer’s Disease (AD-Novel and Unique Pathological Features

    Directory of Open Access Journals (Sweden)

    Yuhai Zhao

    2015-12-01

    Full Text Available Of the approximately ~2.65 × 103 mature microRNAs (miRNAs so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS. This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs for productive miRNA–mRNA interactions and the down-regulation of gene expression. In this article we will: (i consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer’s disease (AD and related forms of chronic neurodegeneration; and (ii highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS.

  11. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer’s Disease (AD)-Novel and Unique Pathological Features

    Science.gov (United States)

    Zhao, Yuhai; Pogue, Aileen I.; Lukiw, Walter J.

    2015-01-01

    Of the approximately ~2.65 × 103 mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA–mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer’s disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS. PMID:26694372

  12. Plasma Cell Cerebrospinal Fluid Pleocytosis Does Not Predict West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    Michael Jordan

    2012-01-01

    Full Text Available Purpose. Diagnosis of WNV (WNV relies upon serologic testing which may take several days after the onset of clinical symptoms to turn positive. Anecdotal reports suggest the presence of plasma cells or plasmacytoid lymphocytes in the cerebrospinal fluid (CSF may be an early indicator of WNV infection. Methods. The CSFs of 89 patients (12 with WNV, 12 with other viral illness {OVI}, and 65 with nonviral illness{NVI} were compared for the presence of either plasma cells or plasmacytoid lymphocytes. Results. Plasma cells were rarely seen in any of the patients. Plasmacytoid lymphocytes were more commonly seen in WNV (58% and OVI (50% than NVI (11%. The differences were significant for WNV versus NVI, but not WNV versus OVI (P<0.001 and P=0.58, resp.. Conclusions. A CSF pleocytosis with plasma cells or plasmacytoid lymphocytes was neither sensitive nor specific for the diagnosis of WNV infection.

  13. Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Wong Nora

    2006-01-01

    Full Text Available Abstract Background Germline mutations of the SDHD, SDHB and SDHC genes, encoding three of the four subunits of succinate dehydrogenase, are a major cause of hereditary paraganglioma and pheochromocytoma, and demonstrate that these genes are classic tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex and a component of both the Krebs cycle and the mitochondrial respiratory chain (succinate:ubiquinone oxidoreductase or complex II. Methods Using conformation sensitive gel electrophoresis (CSGE and direct DNA sequencing to analyse genomic DNA from peripheral blood lymphocytes, here we describe the mutation analysis of the SDHB and SDHC genes in 37 patients with sporadic (i.e. no known family history head and neck paraganglioma and five pheochromocytoma and/or paraganglioma families. Results Two sporadic patients were found to have a SDHB splice site mutation in intron 4, c.423+1G>A, which produces a mis-spliced transcript with a 54 nucleotide deletion, resulting in an 18 amino acid in-frame deletion. A third patient was found to carry the c.214C>T (p.Arg72Cys missense mutation in exon 4 of SDHC, which is situated in a highly conserved protein motif that constitutes the quinone-binding site of the succinate: ubiquinone oxidoreductase (SQR complex in E. coli. Together with our previous results, we found 27 germline mutations of SDH genes in 95 cases (28% of sporadic head and neck paraganglioma. In addition all index patients of five families showing hereditary pheochromocytoma-paraganglioma were found to carry germline mutations of SDHB: four of which were novel, c.343C>T (p.Arg115X, c.141G>A (p.Trp47X, c.281G>A (p.Arg94Lys, and c.653G>C (p.Trp218Ser, and one reported previously, c.136C>T, p.Arg46X. Conclusion In conclusion, these data indicate that germline mutations of SDHB and SDHC play a minor role in sporadic head and neck paraganglioma and further underline the importance of germline SDHB mutations in cases of

  14. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    Directory of Open Access Journals (Sweden)

    Adriana Handra-Luca

    2015-01-01

    Full Text Available Thyroid heterotopic bone formation (HBF in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years. The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.. Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.. The number and size of HBFs (total: 28 ranged between 1 and 23/thyroid gland (one bilateral and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular. The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp. without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm, and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated.

  15. A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Chiò, Adriano; Schymick, Jennifer C; Restagno, Gabriella; Scholz, Sonja W; Lombardo, Federica; Lai, Shiao-Lin; Mora, Gabriele; Fung, Hon-Chung; Britton, Angela; Arepalli, Sampath; Gibbs, J Raphael; Nalls, Michael; Berger, Stephen; Kwee, Lydia Coulter; Oddone, Eugene Z; Ding, Jinhui; Crews, Cynthia; Rafferty, Ian; Washecka, Nicole; Hernandez, Dena; Ferrucci, Luigi; Bandinelli, Stefania; Guralnik, Jack; Macciardi, Fabio; Torri, Federica; Lupoli, Sara; Chanock, Stephen J; Thomas, Gilles; Hunter, David J; Gieger, Christian; Wichmann, H Erich; Calvo, Andrea; Mutani, Roberto; Battistini, Stefania; Giannini, Fabio; Caponnetto, Claudia; Mancardi, Giovanni Luigi; La Bella, Vincenzo; Valentino, Francesca; Monsurrò, Maria Rosaria; Tedeschi, Gioacchino; Marinou, Kalliopi; Sabatelli, Mario; Conte, Amelia; Mandrioli, Jessica; Sola, Patrizia; Salvi, Fabrizio; Bartolomei, Ilaria; Siciliano, Gabriele; Carlesi, Cecilia; Orrell, Richard W; Talbot, Kevin; Simmons, Zachary; Connor, James; Pioro, Erik P; Dunkley, Travis; Stephan, Dietrich A; Kasperaviciute, Dalia; Fisher, Elizabeth M; Jabonka, Sibylle; Sendtner, Michael; Beck, Marcus; Bruijn, Lucie; Rothstein, Jeffrey; Schmidt, Silke; Singleton, Andrew; Hardy, John; Traynor, Bryan J

    2009-04-15

    The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

  16. Somatic Mosaicism Underlies X-linked Acrogigantism (XLAG) Syndrome in Sporadic Male Subjects

    Science.gov (United States)

    Daly, Adrian F.; Yuan, Bo; Fina, Frederic; Caberg, Jean-Hubert; Trivellin, Giampaolo; Rostomyan, Liliya; de Herder, Wouter W.; Naves, Luciana A.; Metzger, Daniel; Cuny, Thomas; Rabl, Wolfgang; Shah, Nalini; Jaffrain-Rea, Marie-Lise; Zatelli, Maria Chiara; Faucz, Fabio R; Castermans, Emilie; Nanni-Metellus, Isabelle; Lodish, Maya; Muhammad, Ammar; Palmeira, Leonor; Potorac, Iulia; Mantovani, Giovanna; Neggers, Sebastian J.; Klein, Marc; Barlier, Anne; Liu, Pengfei; Ouafik, L'Houcine; Bours, Vincent; Lupski, James R.; Stratakis, Constantine A.; Beckers., Albert

    2016-01-01

    Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101. We studied XLAG syndrome patients (N=18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome were identified with Xq26.3 duplications using high definition array comparative genome hybridization (HD-aCGH). We noted males with XLAG had a decreased log2 ratio compared with expected values, suggesting potential mosaicism, while females showed no such decrease. As compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1-53.8%. These characteristics were replicated using a novel, personalized breakpoint-junction specific quantification droplet digital PCR (ddPCR) technique. Using a separate ddPCR technique we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism and identified one female gigantism patient that had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. PMID:26935837

  17. Glycoform-Selective Prion Formation in Sporadic and Familial Forms of Prion Disease

    Science.gov (United States)

    Xiao, Xiangzhu; Yuan, Jue; Haïk, Stéphane; Cali, Ignazio; Zhan, Yian; Moudjou, Mohammed; Li, Baiya; Laplanche, Jean-Louis; Laude, Hubert; Langeveld, Jan; Gambetti, Pierluigi; Kitamoto, Tetsuyuki; Kong, Qingzhong; Brandel, Jean-Philippe; Cobb, Brian A.; Petersen, Robert B.; Zou, Wen-Quan

    2013-01-01

    The four glycoforms of the cellular prion protein (PrPC) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrPSc) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrPSc in the recently identified variably protease-sensitive prionopathy (VPSPr) is the absence of a diglycosylated form, also notable in familial Creutzfeldt-Jakob disease (fCJD), which is linked to mutations in PrP either from Val to Ile at residue 180 (fCJDV180I) or from Thr to Ala at residue 183 (fCJDT183A). Here we report that fCJDV180I, but not fCJDT183A, exhibits a proteinase K (PK)-resistant PrP (PrPres) that is markedly similar to that observed in VPSPr, which exhibits a five-step ladder-like electrophoretic profile, a molecular hallmark of VPSPr. Remarkably, the absence of the diglycosylated PrPres species in both fCJDV180I and VPSPr is likewise attributable to the absence of PrPres glycosylated at the first N-linked glycosylation site at residue 181, as in fCJDT183A. In contrast to fCJDT183A, both VPSPr and fCJDV180I exhibit glycosylation at residue 181 on di- and monoglycosylated (mono181) PrP prior to PK-treatment. Furthermore, PrPV180I with a typical glycoform profile from cultured cells generates detectable PrPres that also contains the diglycosylated PrP in addition to mono- and unglycosylated forms upon PK-treatment. Taken together, our current in vivo and in vitro studies indicate that sporadic VPSPr and familial CJDV180I share a unique glycoform-selective prion formation pathway in which the conversion of diglycosylated and mono181 PrPC to PrPSc is inhibited, probably by a dominant-negative effect, or by other co-factors. PMID:23527023

  18. Equine Immunoglobulin and Equine Neutralizing F(ab')₂ Protect Mice from West Nile Virus Infection.

    Science.gov (United States)

    Cui, Jiannan; Zhao, Yongkun; Wang, Hualei; Qiu, Boning; Cao, Zengguo; Li, Qian; Zhang, Yanbo; Yan, Feihu; Jin, Hongli; Wang, Tiecheng; Sun, Weiyang; Feng, Na; Gao, Yuwei; Sun, Jing; Wang, Yanqun; Perlman, Stanley; Zhao, Jincun; Yang, Songtao; Xia, Xianzhu

    2016-12-18

    West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab')₂ fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab')₂ fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab')₂ passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.

  19. Equine Immunoglobulin and Equine Neutralizing F(ab′2 Protect Mice from West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    Jiannan Cui

    2016-12-01

    Full Text Available West Nile virus (WNV is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′2 fragments from horses immunized with the WNV virus-like particles (VLP expressing the WNV M and E proteins. Immune equine F(ab′2 fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab′2 passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.

  20. Generating West Nile Virus from an Infectious Clone.

    Science.gov (United States)

    Vandergaast, Rianna; Fredericksen, Brenda L

    2016-01-01

    WNV infectious clones are valuable tools for elucidating WNV biology. Nevertheless, relatively few infectious WNV clones have been generated because their construction is hampered by the instability of flaviviral genomes. More recently, advances in cloning techniques as well as the development of several two-plasmid WNV infectious clone systems have facilitated the generation of WNV infectious clones. Here we described a protocol for recovering WNV from a two-plasmid system. In this approach, large quantities of these constructs are digested with restriction enzymes to produce complementary restriction sites at the 3' end of the upstream fragment and the 5' end of the downstream fragment. These fragments are then annealed to produce linear template for in vitro transcription to synthesize infectious RNA. The resulting RNA is transfected into cells and after several days WNV is recovered in the culture supernatant. This method can be used to generate virus from infectious clones encoding high- and low-pathogenicity strains of WNV, as well as chimeric virues.

  1. Potential for Co-Infection of a Mosquito-Specific Flavivirus, Nhumirim Virus, to Block West Nile Virus Transmission in Mosquitoes

    Directory of Open Access Journals (Sweden)

    Silvina Goenaga

    2015-11-01

    Full Text Available Nhumirim virus (NHUV is an insect-specific virus that phylogenetically affiliates with dual-host mosquito-borne flaviviruses. Previous in vitro co-infection experiments demonstrated prior or concurrent infection of Aedes albopictus C6/36 mosquito cells with NHUV resulted in a 10,000-fold reduction in viral production of West Nile virus (WNV. This interference between WNV and NHUV was observed herein in an additional Ae. albopictus mosquito cell line, C7-10. A WNV 2K peptide (V9M mutant capable of superinfection with a pre-established WNV infection demonstrated a comparable level of interference from NHUV as the parental WNV strain in C6/36 and C7-10 cells. Culex quinquefasciatus and Culex pipiens mosquitoes intrathoracically inoculated with NHUVandWNV, or solely withWNVas a control, were allowed to extrinsically incubate the viruses up to nine and 14 days, respectively, and transmissibility and replication of WNV was determined. The proportion of Cx. quinquefasciatus mosquitoes capable of transmitting WNV was significantly lower for the WNV/NHUV group than the WNV control at seven and nine days post inoculation (dpi, while no differences were observed in the Cx. pipiens inoculation group. By dpi nine, a 40% reduction in transmissibility in mosquitoes from the dual inoculation group was observed compared to the WNV-only control. These data indicate the potential that infection of some Culex spp. vectors with NHUV could serve as a barrier for efficient transmissibility of flaviviruses associated with human disease.

  2. Observations of peculiar sporadic sodium structures and their relation with wind variations

    Science.gov (United States)

    Sridharan, S.; Prasanth, P. Vishnu; Kumar, Y. Bhavani; Ramkumar, Geetha; Sathishkumar, S.; Raghunath, K.

    2009-04-01

    Resonance lidar observations of sodium density in the upper mesosphere region over Gadanki (13.5°N, 79.2°E) rarely show complex structures with rapid enhancements of sodium density, completely different from normal sporadic sodium structures. The hourly averaged meteor radar zonal winds over Trivandrum (8.5°N, 76.5°E) show an eastward shear with altitude during the nights, when these events are formed. As suggested by Kane et al. [2001. Joint observations of sodium enhancements and field-aligned ionospheric irregularities. Geophysical Research Letters 28, 1375-1378], our observations show that the complex structures may be formed due to Kelvin-Helmholtz instability, which can occur in the region of strong wind shear.

  3. Long-term preclinical magnetic resonance imaging alterations in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Zanusso, Gianluigi; Camporese, Giulia; Ferrari, Sergio; Santelli, Luca; Bongianni, Matilde; Fiorini, Michele; Monaco, Salvatore; Manara, Renzo; Cagnin, Annachiara

    2016-10-01

    An asymptomatic 74-year-old woman, on follow-up for a carotid body tumor, showed magnetic resonance imaging (MRI) focal restricted diffusion confined to the left temporal and occipital cortices. Thirteen months later, diffusion-weighted images revealed a bilateral cortical ribbon sign involving all lobes. After 1 month, the patient developed gait instability and cognitive decline rapidly evolving to severe dementia and death within 3 months. Prion protein gene sequence, molecular, and neuropathological studies confirmed the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 subtype. Here we show the kinetics of MRI changes and prion spreading in preclinical sCJD MM1. Ann Neurol 2016;80:629-632. © 2016 American Neurological Association.

  4. Differential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients.

    Science.gov (United States)

    Vrabec, Katarina; Boštjančič, Emanuela; Koritnik, Blaž; Leonardis, Lea; Dolenc Grošelj, Leja; Zidar, Janez; Rogelj, Boris; Glavač, Damjan; Ravnik-Glavač, Metka

    2018-01-01

    Genetic studies have managed to explain many cases of familial amyotrophic lateral sclerosis (ALS) through mutations in several genes. However, the cause of a majority of sporadic cases remains unknown. Recently, epigenetics, especially miRNA studies, show some promising aspects. We aimed to evaluate the differential expression of 10 miRNAs, including miR-9, miR-338, miR-638, miR-663a, miR-124a, miR-143, miR-451a, miR-132, miR-206, and let-7b, for which some connection to ALS was shown previously in ALS culture cells, animal models or patients, and in three miRNA host genes, including C1orf61 (miR-9), AATK (miR-338), and DNM2 (miR-638), in leukocyte samples of 84 patients with sporadic ALS. We observed significant aberrant dysregulation across our patient cohort for miR-124a, miR-206, miR-9, let-7b, and miR-638. Since we did not use neurological controls we cannot rule out that the revealed differences in expression of investigated miRNAs are specific for ALS. Nevertheless, the group of these five miRNAs is worth of additional research in leukocytes of larger cohorts from different populations in order to verify their potential association to ALS disease. We also detected a significant up-regulation of the AAKT gene and down-regulation of the DNM2 gene, and thus, for the first time, we connected these with sporadic ALS cases. These findings open up new research toward miRNAs as diagnostic biomarkers and epigenetic processes involved in ALS. The detected significant deregulation of AAKT and DNM2 in sporadic ALS also represents an interesting finding. The DNM2 gene was previously found to be mutated in Charcot-Marie-Tooth neuropathy-type CMT2M and centronuclear myopathy (CNM). In addition, as recent studies connected AATK and frontotemporal dementia (FTD) and DNM2 and hereditary spastic paraplegia (HSP), these two genes together with our results genetically connect, at least in part, five diseases, including FTD, HSP, Charcot-Marie-Tooth (type CMT2M), CNM, and ALS

  5. Clinical evaluation and outcomes of naturally acquired West Nile virus infection in raptors.

    Science.gov (United States)

    Nemeth, Nicole M; Kratz, Gail E; Bates, Rebecca; Scherpelz, Judy A; Bowen, Richard A; Komar, Nicholas

    2009-03-01

    West Nile virus (WNV) infection and associated disease and mortality have been documented in numerous North American raptor species. Information regarding clinical presentations and long-term outcomes of WNV-infected raptors is important in the clinic for the diagnosis, treatment, and assessment of prognosis, as well as for understanding potential population level effects on raptor species. Raptors of 22 species admitted to a rehabilitation clinic were tested, from 2002 to 2005, for previous and acute WNV infection, while comparing clinical syndromes, trauma, and rehabilitation outcomes. Forty-two percent of admitted raptors (132/314) had been infected with WNV, and these presented with a WNV-attributed clinical disease rate of 67.4% (89/132). West Nile virus-infected raptors were less likely to be released (79/132 [59.8%]) than negative raptors (138/182 [75.8%]) and more likely to die or be euthanized (47/132 [35.6%] for WNV-infected vs. 32/182 [17.6%] for WNV-negative). However, WNV-infected raptors with neurologic disease were no less likely to be released (29/53 [54.7%]) than those without neurologic disease (50/79 [63.3%]). Clinical WNV-associated syndromes varied among species. Great horned owls (Bubo virginianus) were more likely to have neurologic signs, whereas American kestrels (Falco sparverius) and Swainson's hawks (Buteo swainsonii) were less likely to have neurologic signs. These results suggest that free-ranging raptors are frequently infected with WNV and that clinical syndromes differ among species. WNV has potentially devastating effects on raptors; however, rehabilitation of WNV-infected raptors can lead to positive outcomes, even for those having had severe neurologic disease.

  6. West Nile Virus: High Transmission Rate in North-Western European Mosquitoes Indicates Its Epidemic Potential and Warrants Increased Surveillance.

    Directory of Open Access Journals (Sweden)

    Jelke J Fros

    Full Text Available West Nile virus (WNV is a highly pathogenic flavivirus transmitted by Culex spp. mosquitoes. In North America (NA, lineage 1 WNV caused the largest outbreak of neuroinvasive disease to date, while a novel pathogenic lineage 2 strain circulates in southern Europe. To estimate WNV lineage 2 epidemic potential it is paramount to know if mosquitoes from currently WNV-free areas can support further spread of this epidemic.We assessed WNV vector competence of Culex pipiens mosquitoes originating from north-western Europe (NWE in direct comparison with those from NA. We exposed mosquitoes to infectious blood meals of lineage 1 or 2 WNV and determined the infection and transmission rates. We explored reasons for vector competence differences by comparing intrathoracic injection versus blood meal infection, and we investigated the influence of temperature. We found that NWE mosquitoes are highly competent for both WNV lineages, with transmission rates up to 25%. Compared to NA mosquitoes, transmission rates for lineage 2 WNV were significantly elevated in NWE mosquitoes due to better virus dissemination from the midgut and a shorter extrinsic incubation time. WNV infection rates further increased with temperature increase.Our study provides experimental evidence to indicate markedly different risk levels between both continents for lineage 2 WNV transmission and suggests a degree of genotype-genotype specificity in the interaction between virus and vector. Our experiments with varying temperatures explain the current localized WNV activity in southern Europe, yet imply further epidemic spread throughout NWE during periods with favourable climatic conditions. This emphasizes the need for intensified surveillance of virus activity in current WNV disease-free regions and warrants increased awareness in clinics throughout Europe.

  7. Studies of sporadic E (Es) associated with the main ionospheric trough

    International Nuclear Information System (INIS)

    Rodger, A.S.; Morrell, C.; Dudeney, J.R.

    1983-01-01

    Sporadic E, or E(s) events under the main F region trough have been confirmed on the basis of ionograms from a vertical incidence ionosonde at Halley Bay, Antarctica. Analyses indicate that E(s) is frequently observable under both the equatorward and the poleward edges of the trough, as well as poleward of it. Before magnetic midnight, E(s) layers whose semithickness resembles those of the normal E layer are common, in contrast to layers seen after magnetic midnight which show the characteristics of thin E(s) layers. A possible explanation of the observed change in the E(s) layer characteristics at magnetic midnight is related to differences in the type and spectra of the precipitating particles. It is shown that the redistribution of ionization by the convection electric field may be important. 40 references

  8. West Nile virus lineage 2 infection in a blood donor from Vienna, Austria, August 2014.

    Science.gov (United States)

    Jungbauer, C; Hourfar, M K; Stiasny, K; Aberle, S W; Cadar, D; Schmidt-Chanasit, J; Mayr, W R

    2015-03-01

    Eastern Austria is neighbouring regions with ongoing West Nile virus (WNV) transmissions. Three human WNV infections had been diagnosed during the past decade in Austria. The Austrian Red Cross Blood Service (ARC-BS) started a first voluntary screening for WNV in blood donors from Eastern Austria by Nucleic Acid Testing (NAT) in June 2014. This is also the most extensive WNV surveillance programme in humans in Austria so far. In August 2014, one autochthonous WNV infection was detected in a blood donor from Vienna. By now, one in 67,800 whole blood donations was found to be positive for WNV RNA. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. The Prognostic Impact of p53 Expression on Sporadic Colorectal Cancer Is Dependent on p21 Status

    International Nuclear Information System (INIS)

    Kruschewski, Martin; Mueller, Kathrin; Lipka, Sybille; Budczies, Jan; Noske, Aurelia; Buhr, Heinz Johannes; Elezkurtaj, Sefer

    2011-01-01

    The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 ± 2.5 months. Expression of p53 was observed in 72 tumors (63%). Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048). No differences were found in recurrence-free survival (p = 0.161). The p53+/p21− combination was seen in 68% (n = 49), the p53+/p21+ combination in 32% (n = 23). Patients with p53+/p21− carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003). Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status

  10. Inhibition of West Nile virus by calbindin-D28k.

    Directory of Open Access Journals (Sweden)

    Venkatraman Siddharthan

    Full Text Available Evidence indicates that West Nile virus (WNV employs Ca(2+ influx for its replication. Moreover, calcium buffer proteins, such as calbindin D28k (CB-D28k, may play an important role mitigating cellular destruction due to disease processes, and more specifically, in some neurological diseases. We addressed the hypothesis that CB-D28k inhibits WNV replication in cell culture and infected rodents. WNV envelope immunoreactivity (ir was not readily co-localized with CB-D28k ir in WNV-infected Vero 76 or motor neuron-like NSC34 cells that were either stably or transiently transfected with plasmids coding for CB-D28k gene. This was confirmed in cultured cells fixed on glass coverslips and by flow cytometry. Moreover, WNV infectious titers were reduced in CB-D28k-transfected cells. As in cell culture studies, WNV env ir was not co-localized with CB-D28k ir in the cortex of an infected WNV hamster, or in the hippocampus of an infected mouse. Motor neurons in the spinal cord typically do not express CB-D28k and are susceptible to WNV infection. Yet, CB-D28k was detected in the surviving motor neurons after the initial phase of WNV infection in hamsters. These data suggested that induction of CB-D28k elicit a neuroprotective response to WNV infection.

  11. Influence of Coding Variability in APP-Aβ Metabolism Genes in Sporadic Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Celeste Sassi

    Full Text Available The cerebral deposition of Aβ42, a neurotoxic proteolytic derivate of amyloid precursor protein (APP, is a central event in Alzheimer's disease (AD(Amyloid hypothesis. Given the key role of APP-Aβ metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Aβ degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test and cumulative (gene-based association test effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 332 sporadic and mainly late-onset AD cases and 676 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, none of which statistically significant after multiple testing correction (1.9e-4sporadic AD.

  12. Uncovering the Rare Variants of DLC1 Isoform 1 and Their Functional Effects in a Chinese Sporadic Congenital Heart Disease Cohort

    Science.gov (United States)

    Wang, Zhen; Tan, Huilian; Kong, Xianghua; Shu, Yang; Zhang, Yuchao; Huang, Yun; Zhu, Yufei; Xu, Heng; Wang, Zhiqiang; Wang, Ping; Ning, Guang; Kong, Xiangyin; Hu, Guohong; Hu, Landian

    2014-01-01

    Congenital heart disease (CHD) is the most common birth defect affecting the structure and function of fetal hearts. Despite decades of extensive studies, the genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1 (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart and essential for heart development according to the knowledge of Dlc1-deficient mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and identified 13 non-synonymous rare variants (including 6 private variants) in the case cohort. Importantly, these rare variants (8/13) were enriched in the N-terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the N-terminal variant positions were conserved among the primates. Among the 9 rare variants that were predicted as “damaging”, five were located at the N-terminal region. Ensuing in vitro functional assays showed that three private variants (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell migration or altered the subcellular location of the protein compared to wild-type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated gene in addition to its role as a tumor suppressor in cancer. PMID:24587289

  13. A review of drug therapy for sporadic fatal insomnia.

    Science.gov (United States)

    Tabaee Damavandi, Pardis; Dove, Martin T; Pickersgill, Richard W

    2017-09-03

    Sporadic fatal insomnia (sFI) is a rapid progressive neurodegenerative disease characterised by gradual to perpetual insomnia, followed by dysautonomia, coma and death. 1 The cause of sFI was recently mapped to a mutation in a protein, the prion, found in the human brain. It is the unfolding of the prion that leads to the generation of toxic oligomers that destroy brain tissue and function. Recent studies have confirmed that a methionine mutation at codon 129 of the human Prion is characteristic of sFI. Current treatment slows down the progression of the disease, but no cure has been found, yet. We used Molecular Docking and Molecular Dynamics simulation methods, to study the toxic Fatal-Insomnia-prion conformations at local unfolding. The idea was to determine these sites and to stabilise these regions against unfolding and miss-folding, using a small ligand, based on a phenothiazine "moiety". As a result we here discuss current fatal insomnia therapy and present seven novel possible compounds for in vitro and in vivo screening.

  14. Immune response to the West Nile virus in aged non-human primates.

    Directory of Open Access Journals (Sweden)

    Anne M Wertheimer

    2010-12-01

    Full Text Available Risk of encephalitis from West Nile virus (WNV infection increases dramatically with age. Understanding the basis of this susceptibility requires development of suitable animal models. Here, we investigated the immune response to WNV in old non-human primates.We investigated clinical, immunological and virological correlates of WNV infection in aging non-human primates. Aged (17-30 yrs and adult (6-9 yrs Rhesus macaques (RM were challenged with WNV in the presence or the absence of the mosquito salivary gland extract (SGE to approximate natural infection. None of the 26 animals exhibited clinical signs of the disease. Quantitative PCR suggested discrete and short-lived viremia, but infectious virus was never isolated. There was markedly increased, age-independent, proliferation of CD3(- non-B cells, followed by B-cell proliferation, which correlated to the loss of detectable WNV genomes. Moreover, animals primed with mosquito salivary gland extract exhibited reduced circulating WNV RNA. While we found the expected age-associated reduction in T cell proliferation, adaptive immunity did not correlate with infection outcome. That was further confirmed in a cohort of thymectomized and/or CD8 T-cell depleted Cynomolgus macaques (CM; N = 15, who also failed to develop WNV disease.Results are consistent with strong and age-independent innate resistance of macaques against WNV challenge. This animal model is therefore not suitable for vaccine and therapeutic testing against WNV. However, understanding the basis of their innate resistance against WNV in macaques could provide helpful clues to improve anti-WNV protection of older adults.

  15. Experimental susceptibility of Wood Ducks (Aix sponsa) for West Nile virus

    Science.gov (United States)

    Hofmeister, Erik K.; Porter, Robert E.; Franson, J. Christian

    2015-01-01

    Detection of West Nile virus (WNV) has been reported in a variety of wild ducks in the US, but little is known about the pathogenesis and outcome of exposure of the disease in these species. Previous experimental studies of WNV in ducks either have challenged a small number of ducks with WNV or have tested domesticated ducks. To determine susceptibility and immune response, we challenged 7-wk-old Wood Ducks (Aix sponsa) with a 1999 American Crow (Corvus brachyrhynchos) isolate of WNV. Wood Ducks were susceptible to infection with the virus, and, although clinical signs or mortality were not observed, microscopic lesions were noted, particularly in the heart and brain. West Nile virus viremia peaked on day 2 postinfection (pi) at 104.54 plaque-forming units (PFU) of virus/mL serum and WNV was shed orally (between 102and 102.9 PFU per swab) and cloacally. Specific anti-WNV antibody response was rapid, with anti-WNV IgM detected on day 3 pi followed on day 5 pi by anti-WNV IgG. Neutralizing antibodies were detected by plaque-reduction neutralization assay in one duck on day 4 pi, and in all sampled ducks on day 5. These results indicate that Wood Ducks are susceptible to WNV, but it is unlikely that significant WNV mortality events occur in Wood Ducks or that ducks play a significant role in transmission. However, WNV viremia was sufficient, in theory, to infect mosquitoes, and oral and cloacal shedding of the virus may increase the risk of infection to other waterbirds.

  16. Mosquito Surveillance for 15 Years Reveals High Genetic Diversity Among West Nile Viruses in Israel.

    Science.gov (United States)

    Lustig, Yaniv; Hindiyeh, Musa; Orshan, Laor; Weiss, Leah; Koren, Ravit; Katz-Likvornik, Shiri; Zadka, Hila; Glatman-Freedman, Aharona; Mendelson, Ella; Shulman, Lester M

    2016-04-01

    West Nile Virus (WNV) is endemic in Israel and has been the cause of several outbreaks in recent years. In 2000, a countrywide mosquito survey was established to monitor WNV activity and characterize viral genotypes in Israel. We analyzed data from 7135 pools containing 277 186 mosquitoes collected over the past 15 years and, here, report partial sequences of WNV genomes obtained from 102 of the 336 positive mosquito pools. Phylogenetic analysis demonstrated that cluster 4 and the Mediterranean and Eastern European subtypes of cluster 2 within WNV lineage 1 circulated in Israel, as did WNV lineage 2, highlighting a high genetic diversity of WNV genotypes in our region. As a major crossroads for bird migration between Africa and Eurasia and with a long history of human infection, Israel serves as a resource hub for WNV in Africa and Eurasia and provides valuable information on WNV circulation in these regions. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. Sporadic Creutzfeldt-Jakob disease in a native Puerto Rican patient.

    Science.gov (United States)

    Del Pilar-Morales, Esteban A; Cali, Ignazio; Chapas, Javier; Bertrán-Pasarell, Jorge; Puoti, Gianfranco; Gambetti, Pierluigi; Nobo, Ulises

    2015-03-01

    The diagnosis of Creutzfeldt-Jakob disease (CJD) is often a challenge for most physicians given its extremely low incidence and different clinico-pathological presentations. We report the case of a 56-year old patient native to Puerto Rico suspected of sporadic Creutzfeldt-Jakob disease (sCD). The symptoms at onset were notorious for bilateral cortical blindness followed by rapidly progressive cognitive decline, visual deficit, increased levels of CSF 14-3-3 and tau along with positive brain MRI and EEG, are highly indicative of CJD. The definite diagnosis was confirmed by the National Prion Disease Pathology Surveillance Center (NPDPSC), in Cleveland, Ohio, USA. Lack of genetic mutations in the prion protein (PrP) gene, widespread histopathological changes and the accumulation of scrapie PrP (PrPSc) in the brain confirmed the diagnosis of sCJD. The patient, admitted to our institution in 2011, represents the first detailed report of sCJD in a native Puerto Rican patient living in Puerto Rico.

  18. MRI manifestation for the diagnosis of sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Xue Yonggang; Qi Ji; Xia Shuang

    2007-01-01

    Objective: To study the MRI features of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Three patients with clinically diagnosed sCJD underwent MR study, including SE T 1 WI, FSE T 2 WI, and DWI sequences. The MR imaging features were analyzed. Results: The lesions were not definite either in SE T 1 WI or in FSE T 2 WI, but were prominent in DWI. Abnormal hyperintensive signal appeared in the cerebral cortex, with the frontal, parietal, and occipital lobes being the mostly involved region. The subcortical white matter was normal. The bilateral caudate nuclei and thalami could also be involved. The abnormal signal could be either symmetrical or asymmetrical. There was diffuse atrophy of the brain parenchyma in the late phase of disease, especially in the cortex. Conclusion: With the application of MR study, especially the DWI, combined with its characteristic clinical manifestation, the diagnosis of sCJD can be made definitely. (authors)

  19. Analysis of wave-like oscillations in parameters of sporadic E layer and neutral atmosphere

    Science.gov (United States)

    Mošna, Z.; Koucká Knížová, P.

    2012-12-01

    The present study mainly concerns the wave-like activity in the ionospheric sporadic E layer (Es) and in the lower lying stratosphere. The proposed analysis involves parameters describing the state of plasma in the sporadic E layer. Critical frequencies foEs and layer heights hEs were measured at the Pruhonice station (50°N, 14.5°E) during summer campaigns 2004, 2006 and 2008. Further, we use neutral atmosphere (temperature data at 10 hPa) data from the same time interval. The analysis concentrates on vertically propagating wave-like structures within distant atmospheric regions. By means of continuous wavelet transform (CWT) we have detected significant wave-like oscillation at periods covering tidal and planetary oscillation domains both in the Es layer parameters (some of them were reported earlier, for instance in works of Abdu et al., 2003; Pancheva and Mitchel, 2004; Pancheva et al., 2003; Šauli and Bourdillon, 2008) and in stratospheric temperature variations. Further analyses using cross wavelet transform (XWT) and wavelet coherence analysis (WTC) show that despite high wave-like activity in a wide period range, there are only limited coherent wave-like bursts present in both spectra. Such common coherent wave bursts occur on periods close to eigen-periods of the terrestrial atmosphere. We suppose that vertical coupling between atmospheric regions realized by vertically propagating planetary waves occurs predominantly on periods close to those of Rossby modes. Analysis of the phase shift between data from distant atmospheric regions reveals high variability and very likely supports the non-linear scenario of the vertical coupling provided by planetary waves.

  20. AcEST: BP918385 [AcEST

    Lifescience Database Archive (English)

    Full Text Available H TCP10 (Fragment) OS=Arabidopsis thaliana ... 34 4.1 tr|Q6WNV6|Q6WNV6_9REOV VP3 OS=Avian rotavirus... HQ+T + H + + SS F Sbjct: 122 HQTTSDHHHHHQNQASSMF 140 >tr|Q6WNV6|Q6WNV6_9REOV VP3 OS=Avian rotavirus A PE=4

  1. West Nile virus circulation in South-Eastern Romania, 2011 to 2013.

    Science.gov (United States)

    Dinu, S; Cotar, A I; Pănculescu-Gătej, I R; Fălcuţă, E; Prioteasa, F L; Sîrbu, A; Oprişan, G; Bădescu, D; Reiter, P; Ceianu, C S

    2015-05-21

    Lineage 2 West Nile virus (WNV), previously found only in sub-Saharan Africa and Madagascar, was identified in Hungary in 2004 and has rapidly expanded in Europe in the past decade. Following a significant outbreak of West Nile fever with neurological cases caused by lineage 1 WNV in Romania in 1996, scattered cases have been recorded in the south-east of the country in each transmission season. Another outbreak, affecting a larger area and caused by lineage 2 WNV, was recorded in 2010. We analysed human sera from neuroinvasive West Nile fever cases and mosquitoes, sampled in south-eastern Romania between 2011 and 2013, for the presence of WNV genome, and obtained partial NS5 and envelope glycoprotein sequences. Human- and mosquito-derived WNV sequences were highly similar (99%) to Volgograd 2007 lineage 2 WNV and differed from isolates previously detected in central and southern Europe. WNV was detected in one pool of Culex pipiens s.l. males, documenting vertical transmission. Lineage 4 WNV, of unknown pathogenicity to mammals, was found in the amphibian-feeding mosquito Uranotaenia unguiculata from the Danube Delta. Our results present molecular evidence for the maintenance of the same isolates of Volgograd 2007-like lineage 2 WNV in south-eastern Romania between 2011 and 2013.

  2. Surveillance potential of non-native Hawaiian birds for detection of West Nile Virus

    Science.gov (United States)

    Hofmeister, Erik K.; Dusek, Robert J.; Brand, Christopher J.

    2015-01-01

    West Nile virus (WNV) was first detected in North America in 1999. Alaska and Hawaii (HI) remain the only U.S. states in which transmission of WNV has not been detected. Dead bird surveillance has played an important role in the detection of the virus geographically, as well as temporally. In North America, corvids have played a major role in WNV surveillance; however, the only corvid in HI is the endangered Hawaiian crow that exists only in captivity, thus precluding the use of this species for WNV surveillance in HI. To evaluate the suitability of alternate avian species for WNV surveillance, we experimentally challenged seven abundant non-native bird species present in HI with WNV and compared mortality, viremia, oral shedding of virus, and seroconversion. For detection of WNV in oral swabs, we compared viral culture, reverse-transcriptase polymerase chain reaction, and the RAMP® test. For detection of antibodies to WNV, we compared an indirect and a competitive enzyme-linked immunoassay. We found four species (house sparrow, house finch, Japanese white-eye, and Java sparrow) that may be useful in dead bird surveillance for WNV; while common myna, zebra dove, and spotted dove survived infection and may be useful in serosurveillance.

  3. The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease

    DEFF Research Database (Denmark)

    Bahl, Justyna Maria Czarna; Heegaard, Niels Henrik Helweg; Falkenhorst, Gerhard

    2009-01-01

    ) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE......Laboratory markers have a prominent place among the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF...

  4. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases.

    Science.gov (United States)

    Lanoiselée, Hélène-Marie; Nicolas, Gaël; Wallon, David; Rovelet-Lecrux, Anne; Lacour, Morgane; Rousseau, Stéphane; Richard, Anne-Claire; Pasquier, Florence; Rollin-Sillaire, Adeline; Martinaud, Olivier; Quillard-Muraine, Muriel; de la Sayette, Vincent; Boutoleau-Bretonniere, Claire; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Sarazin, Marie; le Ber, Isabelle; Epelbaum, Stéphane; Jonveaux, Thérèse; Rouaud, Olivier; Ceccaldi, Mathieu; Félician, Olivier; Godefroy, Olivier; Formaglio, Maite; Croisile, Bernard; Auriacombe, Sophie; Chamard, Ludivine; Vincent, Jean-Louis; Sauvée, Mathilde; Marelli-Tosi, Cecilia; Gabelle, Audrey; Ozsancak, Canan; Pariente, Jérémie; Paquet, Claire; Hannequin, Didier; Campion, Dominique

    2017-03-01

    Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. We report here a novel update (2012-2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers-total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42-in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole

  5. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases.

    Directory of Open Access Journals (Sweden)

    Hélène-Marie Lanoiselée

    2017-03-01

    Full Text Available Amyloid protein precursor (APP, presenilin-1 (PSEN1, and presenilin-2 (PSEN2 mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD. Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series.We report here a novel update (2012-2016 of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD with an age of onset (AOO ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y. APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%. Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2 identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF biomarkers, 46 (87% had all three CSF biomarkers-total tau protein (Tau, phospho-tau protein (P-Tau, and amyloid β (Aβ42-in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification.Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the

  6. Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype

    NARCIS (Netherlands)

    Pinto, Mafalda; Wub, Ying; Mensink, Rob G. J.; Cirnes, Luis; Seruca, Raquel; Hofstra, Robert M. W.

    2008-01-01

    In hereditary nonpolyposis colorectal cancer (HNPCC), patients' mismatch repair (MMR) gene mutations cause MMR deficiency, leading to microsatellite instability (MSI-H). MSI-H is also found in a substantial fraction of sporadic gastric carcinomas (SGC), mainly due to MLH1 promoter hypermethylation,

  7. Effects of blood-flow-restricted resistance training on muscle function in a 74-year-old male with sporadic inclusion body myositis

    DEFF Research Database (Denmark)

    Jørgensen, Anders Nørkær; Aagaard, P; Nielsen, J L

    2016-01-01

    Sporadic inclusion body myositis (sIBM) is a systemic disease that is characterized by substantial skeletal muscle weakness and muscle inflammation, leading to impaired physical function. The objective was to investigate the effect of low-load resistance exercise with concurrent partial blood flow...

  8. Observations of neutral winds, wind shears, and wave structure during a sporadic-E/QP event

    Directory of Open Access Journals (Sweden)

    M. F. Larsen

    2005-10-01

    Full Text Available The second Sporadic E Experiment over Kyushu (SEEK-2 was carried out on 3 August 2002, during an active sporadic-E event that also showed quasi-periodic (QP echoes. Two rockets were launched into the event from Kagoshima Space Center in southern Japan 15 min apart. Both carried a suite of instruments, but the second rocket also released a trimethyl aluminum (TMA trail to measure the neutral winds and turbulence structure. In a number of earlier measurements in similar conditions, large winds and shears that were either unstable or close to instability were observed in the altitude range where the ionization layer occurred. The SEEK-2 wind measurements showed similar vertical structure, but unlike earlier experiments, there was a significant difference between the up-leg and down-leg wind profiles. In addition, wave or billow-like fluctuations were evident in the up-leg portion of the trail, while the lower portion of the down-leg trail was found to have extremely strong turbulence that led to a rapid break-up of the trail. The large east-west gradient in the winds and the strong turbulence have not been observed before. The wind profiles and shears, as well as the qualitative characteristics of the strong turbulence are presented, along with a discussion of the implications of the dynamical features. Keywords. Ionosphere (Mid-latitude ionosphere; Ionospheric irregularities; Electric field and currents

  9. Regression of sporadic intra-abdominal desmoid tumour following administration of non-steroidal anti-inflammatory drug

    Directory of Open Access Journals (Sweden)

    Fujiwara Yoshinori

    2008-02-01

    Full Text Available Abstract Background Desmoid tumours or fibromatoses are rare entities characterized by the benign proliferation of fibroblasts, which can be life-threatening due to their locally aggressive properties. Surgery is widely accepted as the first line of treatment for extra-abdominal desmoids; however, it is not recommended for intra-abdominal desmoids because of the high-risk of recurrence and difficulties with the operation. Here, we report on a patient with sporadic intra-abdominal desmoid tumours, who showed partial response following the intake of non-steroidal anti-inflammatory drugs. Case presentation A 73-year-old man presented with swelling and pain of the right leg. Computed tomography showed an abnormal multilocular soft-tissue mass (95 × 70 mm in the right pelvis, which was revealed by biopsy to be a desmoid tumour. Immunohistochemical analysis showed that the tumour cells expressed vimentin, but not smooth-muscle actin, CD34, or desmin. Very few Ki-67-positive cells were found. Non-cytotoxic treatment with etodolac (200 mg/day was chosen because of the patient's age, lack of bowel obstruction, and the likelihood of prostate cancer. Two years after the commencement of non-steroidal anti-inflammatory drug administration, computed tomography showed a decrease in tumour size (63 × 49 mm, and the disappearance of intratumoural septa. Conclusion Our case report suggests that non-steroidal anti-inflammatory drug treatment should be taken into consideration for use as first-line treatment in patients with sporadic intra-abdominal desmoid tumours.

  10. Regression of sporadic intra-abdominal desmoid tumour following administration of non-steroidal anti-inflammatory drug

    Science.gov (United States)

    Tanaka, Keita; Yoshikawa, Reigetsu; Yanagi, Hidenori; Gega, Makoto; Fujiwara, Yoshinori; Hashimoto-Tamaoki, Tomoko; Hirota, Syozo; Tsujimura, Tohru; Tomita, Naohiro

    2008-01-01

    Background Desmoid tumours or fibromatoses are rare entities characterized by the benign proliferation of fibroblasts, which can be life-threatening due to their locally aggressive properties. Surgery is widely accepted as the first line of treatment for extra-abdominal desmoids; however, it is not recommended for intra-abdominal desmoids because of the high-risk of recurrence and difficulties with the operation. Here, we report on a patient with sporadic intra-abdominal desmoid tumours, who showed partial response following the intake of non-steroidal anti-inflammatory drugs. Case presentation A 73-year-old man presented with swelling and pain of the right leg. Computed tomography showed an abnormal multilocular soft-tissue mass (95 × 70 mm) in the right pelvis, which was revealed by biopsy to be a desmoid tumour. Immunohistochemical analysis showed that the tumour cells expressed vimentin, but not smooth-muscle actin, CD34, or desmin. Very few Ki-67-positive cells were found. Non-cytotoxic treatment with etodolac (200 mg/day) was chosen because of the patient's age, lack of bowel obstruction, and the likelihood of prostate cancer. Two years after the commencement of non-steroidal anti-inflammatory drug administration, computed tomography showed a decrease in tumour size (63 × 49 mm), and the disappearance of intratumoural septa. Conclusion Our case report suggests that non-steroidal anti-inflammatory drug treatment should be taken into consideration for use as first-line treatment in patients with sporadic intra-abdominal desmoid tumours. PMID:18257933

  11. N-acetyl transferase 2/environmental factors and their association as a modulating risk factor for sporadic colon and rectal cancer.

    Science.gov (United States)

    Procopciuc, Lucia M; Osian, Gelu; Iancu, Mihaela

    2017-09-01

    The aim of this study was to evaluate the association between environmental factors and colon or rectal cancer after adjusting for N-acetyl transferase 2 (NAT2) phenotypes. Ninety-six patients with sporadic colon cancer, 54 with sporadic rectal cancer and 162 control subjects were genotyped for NAT2-T341C, G590A, G857A, A845C, and C481T using sequencing and PCR-RFLP analysis. The risk for colon cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, and NAT2*5A-C481T. The risk for rectal cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*7B-G857A, and NAT2*5A-C481T. High fried red meat intake associated with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele determines a risk of 2.39 (P=.002), 2.39 (P=.002), 2.37 (P=.002), 2.28 (P=.004), and 2.51 (P=.001), respectively, for colon cancer, whereas in the case of rectal cancer, the risk increased to 7.55 (Pcolon cancer, whereas the risk for rectal cancer is 9.72 (Pcolon cancer. Fried red meat, alcohol, and smoking increase the risk of sporadic CRC, especially of colon cancer, in the case of rapid acetylators for the NAT2 variants. © 2016 Wiley Periodicals, Inc.

  12. Detection of West Nile virus lineage 2 in the urine of acute human infections.

    Science.gov (United States)

    Papa, Anna; Testa, Theodolinda; Papadopoulou, Elpida

    2014-12-01

    West Nile virus (WNV) lineage 2 emerged in Greece in 2010 and since then outbreaks in humans have been reported for four consecutive years. Laboratory diagnosis is based mainly on serology. A real-time RT-PCR was applied on urine samples obtained from 35 patients with acute WNV infection. WNV RNA was detected in 40% of the samples with cycle threshold (CT) values ranging from 26.95 to 39.89 (mean 33.11). WNV was isolated from two of four urine samples with low CT (sample shipment and storage conditions are very important for virus detection and isolation. The usefulness of the WNV RNA detection in urine as a diagnostic tool of acute WNV infections is discussed. © 2014 Wiley Periodicals, Inc.

  13. A quantitative study of the neuropathology of 32 sporadic and familial cases of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP).

    Science.gov (United States)

    Armstrong, R A; Carter, D; Cairns, N J

    2012-02-01

    To further characterize the neuropathology of the heterogeneous molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). We quantified the neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe using a phosphorylation-independent TDP-43 antibody in 32 cases of FTLD-TDP comprising sporadic and familial cases, with associated pathology such as hippocampal sclerosis (HS) or Alzheimer's disease (AD), and four neuropathological subtypes using TDP-43 immunohistochemistry. Analysis of variance (anova) was used to compare differences between the various groups of cases. These data from FTLD-TDP cases demonstrate quantitative differences in pathological features between: (i) regions of the frontal and temporal lobe; (ii) upper and lower cortex; (iii) sporadic and progranulin (GRN) mutation cases; (iv) cases with and without AD or HS; and (v) between assigned subtypes. The data confirm that the dentate gyrus is a major site of neuropathology in FTLD-TDP and that most laminae of the cerebral cortex are affected. GRN mutation cases are quantitatively different from sporadic cases, while cases with associated HS and AD have increased densities of dystrophic neurites and abnormally enlarged neurones respectively. There is little correlation between the subjective assessment of subtypes and the more objective quantitative data. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

  14. A prospective evaluation of laparoscopic exploration with intraoperative ultrasound as a technique for localizing sporadic insulinomas.

    Science.gov (United States)

    Grover, Amelia C; Skarulis, Monica; Alexander, H Richard; Pingpank, James F; Javor, Edward D; Chang, Richard; Shawker, Thomas; Gorden, Phil; Cochran, Craig; Libutti, Steven K

    2005-12-01

    Preoperative imaging studies localize insulinomas in less than 50% of patients. Arteriography with calcium stimulation and venous sampling (ASVS) regionalizes greater than 90% of insulinomas but requires specialized expertise and an invasive procedure. This prospective study evaluated laparoscopic exploration with IOUS compared with the other localization procedures in patients with a sporadic insulinoma. Between March 2001 and October 2004, 14 patients (7 women and 7 men; mean age, 53) with an insulinoma were enrolled in an IRB-approved protocol. Computed tomography, magnetic resonance imaging, ultrasound scan, and arteriography with calcium stimulation and venous sampling were performed preoperatively. A surgeon, blinded to the results of the localizing studies, performed a laparoscopic exploration with intraoperative ultrasound (IOUS). At the completion of the exploration, the success of laparoscopy for localization was scored, and the tumor was resected. Twelve of 14 tumors were localized successfully before laparoscopy (noninvasive, 7 of 14; invasive, 11 of 14). Laparoscopic IOUS localized successfully 12 of 14 tumors. All lesions were resected, and all patients were cured (median follow-up, 36 months). Laparoscopic IOUS identified 86% of tumors. The authors consider laparoscopic IOUS to be equivalent to ASVS in localizing insulinomas. Further study is therefore warranted to determine the role of laparoscopy with IOUS in the localization and treatment algorithm for patients with sporadic insulinoma.

  15. Sporadic Creutzfeldt-Jakob Disease MM1+2C and MM1 are Identical in Transmission Properties.

    Science.gov (United States)

    Kobayashi, Atsushi; Matsuura, Yuichi; Iwaki, Toru; Iwasaki, Yasushi; Yoshida, Mari; Takahashi, Hitoshi; Murayama, Shigeo; Takao, Masaki; Kato, Shinsuke; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

    2016-01-01

    The genotype (methionine, M or valine, V) at polymorphic codon 129 of the PRNP gene and the type (1 or 2) of abnormal prion protein in the brain are the major determinants of the clinicopathological features of sporadic Creutzfeldt-Jakob disease (CJD), thus providing molecular basis for classification of sporadic CJD, that is, MM1, MM2, MV1, MV2, VV1 or VV2. In addition to these "pure" cases, "mixed" cases presenting mixed neuropathological and biochemical features have also been recognized. The most frequently observed mixed form is the co-occurrence of MM1 and MM2, namely MM1+2. However, it has remained elusive whether MM1+2 could be a causative origin of dura mater graft-associated CJD (dCJD), one of the largest subgroups of iatrogenic CJD. To test this possibility, we performed transmission experiments of MM1+2 prions and a systematic neuropathological examination of dCJD patients in the present study. The transmission properties of the MM1+2 prions were identical to those of MM1 prions because MM2 prions lacked transmissibility. In addition, the neuropathological characteristics of MM2 were totally absent in dCJD patients examined. These results suggest that MM1+2 can be a causative origin of dCJD and causes neuropathological phenotype similar to that of MM1. © 2015 International Society of Neuropathology.

  16. Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases.

    Directory of Open Access Journals (Sweden)

    Alexandra V Stavropoulou

    Full Text Available Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24. In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6% of familial cancer cases and in 27/592 (4.6% of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%. The majority of BRCA1 carriers (71.2% presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer.

  17. Vector Contact Rates on Eastern Bluebird Nestlings Do Not Indicate West Nile Virus Transmission in Henrico County, Virginia, USA

    Directory of Open Access Journals (Sweden)

    Kevin A. Caillouët

    2013-11-01

    Full Text Available Sensitive indicators of spatial and temporal variation in vector-host contact rates are critical to understanding the transmission and eventual prevention of arboviruses such as West Nile virus (WNV. Monitoring vector contact rates on particularly susceptible and perhaps more exposed avian nestlings may provide an advanced indication of local WNV amplification. To test this hypothesis we monitored WNV infection and vector contact rates among nestlings occupying nest boxes (primarily Eastern bluebirds; Sialia sialis, Turdidae across Henrico County, Virginia, USA, from May to August 2012. Observed host-seeking rates were temporally variable and associated with absolute vector and host abundances. Despite substantial effort to monitor WNV among nestlings and mosquitoes, we did not detect the presence of WNV in these populations. Generally low vector-nestling host contact rates combined with the negative WNV infection data suggest that monitoring transmission parameters among nestling Eastern bluebirds in Henrico County, Virginia, USA may not be a sensitive indicator of WNV activity.

  18. Differential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients

    Directory of Open Access Journals (Sweden)

    Katarina Vrabec

    2018-04-01

    Full Text Available Genetic studies have managed to explain many cases of familial amyotrophic lateral sclerosis (ALS through mutations in several genes. However, the cause of a majority of sporadic cases remains unknown. Recently, epigenetics, especially miRNA studies, show some promising aspects. We aimed to evaluate the differential expression of 10 miRNAs, including miR-9, miR-338, miR-638, miR-663a, miR-124a, miR-143, miR-451a, miR-132, miR-206, and let-7b, for which some connection to ALS was shown previously in ALS culture cells, animal models or patients, and in three miRNA host genes, including C1orf61 (miR-9, AATK (miR-338, and DNM2 (miR-638, in leukocyte samples of 84 patients with sporadic ALS. We observed significant aberrant dysregulation across our patient cohort for miR-124a, miR-206, miR-9, let-7b, and miR-638. Since we did not use neurological controls we cannot rule out that the revealed differences in expression of investigated miRNAs are specific for ALS. Nevertheless, the group of these five miRNAs is worth of additional research in leukocytes of larger cohorts from different populations in order to verify their potential association to ALS disease. We also detected a significant up-regulation of the AAKT gene and down-regulation of the DNM2 gene, and thus, for the first time, we connected these with sporadic ALS cases. These findings open up new research toward miRNAs as diagnostic biomarkers and epigenetic processes involved in ALS. The detected significant deregulation of AAKT and DNM2 in sporadic ALS also represents an interesting finding. The DNM2 gene was previously found to be mutated in Charcot-Marie-Tooth neuropathy-type CMT2M and centronuclear myopathy (CNM. In addition, as recent studies connected AATK and frontotemporal dementia (FTD and DNM2 and hereditary spastic paraplegia (HSP, these two genes together with our results genetically connect, at least in part, five diseases, including FTD, HSP, Charcot-Marie-Tooth (type CMT2M, CNM

  19. Culex pipiens and Stegomyia albopicta (= Aedes albopictus) populations as vectors for lineage 1 and 2 West Nile virus in Europe.

    Science.gov (United States)

    Brustolin, M; Talavera, S; Santamaría, C; Rivas, R; Pujol, N; Aranda, C; Marquès, E; Valle, M; Verdún, M; Pagès, N; Busquets, N

    2016-06-01

    The emerging disease West Nile fever is caused by West Nile virus (WNV), one of the most widespread arboviruses. This study represents the first test of the vectorial competence of European Culex pipiens Linnaeus 1758 and Stegomyia albopicta (= Aedes albopictus) (both: Diptera: Culicidae) populations for lineage 1 and 2 WNV isolated in Europe. Culex pipiens and S. albopicta populations were susceptible to WNV infection, had disseminated infection, and were capable of transmitting both WNV lineages. This is the first WNV competence assay to maintain mosquito specimens under environmental conditions mimicking the field (day/night) conditions associated with the period of maximum expected WNV activity. The importance of environmental conditions is discussed and the issue of how previous experiments conducted in fixed high temperatures may have overestimated WNV vector competence results with respect to natural environmental conditions is analysed. The information presented should be useful to policymakers and public health authorities for establishing effective WNV surveillance and vector control programmes. This would improve preparedness to prevent future outbreaks. © 2016 The Authors. Medical and Veterinary Entomology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.

  20. Blood group A and Rh(D)-negativity are associated with symptomatic West Nile virus infection

    Science.gov (United States)

    Kaidarova, Zhanna; Bravo, Marjorie D.; Kamel, Hany T.; Custer, Brian S; Busch, Michael P.; Lanteri, Marion C.

    2016-01-01

    Background West Nile virus (WNV) infection is mostly asymptomatic but 20% of subjects report WNV fever and 1% of patients experience neurological diseases with higher rates in elderly and immunosuppressed persons. With no treatment and no vaccine to prevent the development of symptomatic infections, it is essential to understand prognostic factors influencing symptomatic disease outcome. Host genetic background has been linked to the development of WNV neuroinvasive disease. The present study investigates the association between the ABO and Rh(D) blood group status and WNV disease outcome. Study Design and Methods The distribution of blood groups was investigated within a cohort of 374 WNV+ blood donors including 244 asymptomatic (AS) and 130 symptomatic (S) WNV+ blood donors. Logistic regression analyses were used to examine associations between A, B, O and Rh(D) blood groups and WNV clinical disease outcome. Results Symptomatic WNV+ donors exhibited increased frequencies of blood group A (S 47.6% AS 36.8%, P=0.04, OR [95%CI] 1.56 [1.01–2.40]) and Rh(D)-negative individuals (S 21.5% AS 13.1%, P=0.03, OR [95%CI] 1.82 [1.04–3.18]). Conclusion The findings suggest a genetic susceptibility placing blood group A and Rh(D)-negative individuals at risk for the development of symptomatic disease outcome after WNV infection. PMID:27189860

  1. Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease.

    Science.gov (United States)

    Ancliff, P J; Gale, R E; Liesner, R; Hann, I M; Linch, D C

    2001-11-01

    Severe congenital neutropenia (SCN) was originally described as an autosomal recessive disorder. Subsequently, autosomal dominant and sporadic forms of the disease have been recognized. All forms are manifest by persistent severe neutropenia and recurrent bacterial infection. In contrast, cyclical hematopoiesis is characterized by periodic neutropenia inter-spaced with (near) normal neutrophil counts. Recently, linkage analysis on 13 affected pedigrees identified chromosome 19p13.3 as the likely position for mutations in cyclical hematopoiesis. Heterozygous mutations in the ELA2 gene encoding neutrophil elastase were detected in all families studied. Further work also demonstrated mutations in ELA2 in sporadic and autosomal dominant SCN. However, all mutations described to date are heterozygous and thus appear to act in a dominant fashion, which is inconsistent with an autosomal recessive disease. Therefore, the current study investigated whether mutations in ELA2 could account for the disease phenotype in classical autosomal recessive SCN and in the sporadic and autosomal dominant types. All 5 exons of ELA2 and their flanking introns were studied in 18 patients (3 autosomal recessive, 5 autosomal dominant [from 3 kindreds], and 10 sporadic) using direct automated sequencing. No mutations were found in the autosomal recessive families. A point mutation was identified in 1 of 3 autosomal dominant families, and a base substitution was identified in 8 of 10 patients with the sporadic form, though 1 was subsequently shown to be a low-frequency polymorphism. These results suggest that mutations in ELA2 are not responsible for classical autosomal recessive Kostmann syndrome but provide further evidence for the role of ELA2 in SCN.

  2. Multilocus Variable-Number Tandem-Repeat Analysis, Pulsed-Field Gel Electrophoresis, and Antimicrobial Susceptibility Patterns in Discrimination of Sporadic and Outbreak-Related Strains of Yersinia enterocolitica

    Directory of Open Access Journals (Sweden)

    Skurnik Mikael

    2011-02-01

    Full Text Available Abstract Background We assessed the potential of multilocus variable-number tandem-repeat analysis (MLVA, pulsed-field gel electrophoresis (PFGE, and antimicrobial susceptibility testing for discriminating 104 sporadic and outbreak-related Yersinia enterocolitica (YE bio/serotype 3-4/O:3 and 2/O:9 isolates. MLVA using six VNTR markers was performed in two separate multiplex PCRs, and the fluorescently labeled PCR products were accurately sized on an automated DNA sequencer. Results MLVA discriminated 82 sporadic YE 3-4/O:3 and 2/O:9 strains into 77 types, whereas PFGE with the restriction enzyme NotI discriminated the strains into 23 different PFGE pulsotypes. The discriminatory index for a sporadic strain was 0.862 for PFGE and 0.999 for MLVA. MLVA confirmed that a foodborne outbreak in the city of Kotka, Finland in 2003 had been caused by a multiresistant YE 4/O:3 strain that was distinctly different from those of epidemiologically unrelated strains with an identical PFGE pulsotype. The multiresistance of Y. enterocolitica strains (19% of the sporadic strains correlated significantly (p = 0.002 with travel abroad. All of the multiresistant Y. enterocolitica strains belonged to four PFGE pulsotypes that did not contain any susceptible strains. Resistance to nalidixic acid was related to changes in codons 83 or 87 that stemmed from mutations in the gyrA gene. The conjugation experiments demonstrated that resistance to CHL, STR, and SUL was carried by a conjugative plasmid. Conclusions MLVA using six loci had better discriminatory power than PFGE with the NotI enzyme. MLVA was also a less labor-intensive method than PFGE and the results were easier to analyze. The conjugation experiments demonstrated that a resistance plasmid can easily be transferred between Y. enterocolitica strains. Antimicrobial multiresistance of Y. enterocolitica strains was significantly associated with travel abroad.

  3. Pathology and epidemiology of natural West Nile viral infection of raptors in Georgia.

    Science.gov (United States)

    Ellis, Angela E; Mead, Daniel G; Allison, Andrew B; Stallknecht, David E; Howerth, Elizabeth W

    2007-04-01

    Carcasses from 346 raptors found between August 2001 and December 2004 were tested for West Nile virus (WNV) using virus isolation and immunohistochemistry; 40 were positive for WNV by one or both methods. Of these 40 birds, 35 had histologic lesions compatible with WNV infection, one had lesions possibly attributable to WNV, and four had no histologic evidence of WNV. The most common histologic lesions associated with WNV infection were myocardial inflammation, necrosis, and fibrosis; skeletal muscle degeneration, inflammation, and fibrosis; and lymphoplasmacytic encephalitis. Other lesions included hepatitis, lymphoid depletion in spleen and bursa, splenic and hepatic hemosiderosis, pancreatitis, and ganglioneuritis. Gross lesions included calvarial and leptomeningeal hemorrhage, myocardial pallor, and splenomegaly. Red-tailed hawks (Buteo jamaicensis) (10/56), sharp-shinned hawks (Accipiter striatus) (8/40), and Cooper's hawks (Accipiter cooperii) (10/103) were most commonly affected. Also affected were red-shouldered hawks (Buteo lineatus) (2/43), an osprey (Pandion haliaetus) (1/5), barred owls (Strix varia) (4/27), a great horned owl (Bubo virginianus) (1/18), and eastern screech owls (Megascops asio) (4/42). Although birds were examined throughout the year, positive cases occurred only during the summer and late fall (June-December). Yearly WNV mortality rates ranged from 7-15% over the four years of the study. This study indicates trends in infection rates of WNV in raptorial species over a significant time period and supports the available information regarding pathology of WNV infection in Strigiformes and Falconiformes. Although many species tested were positive for WNV infection, severity of lesions varied among species.

  4. Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: a matched cohort study with sporadic vestibular schwannomas.

    Science.gov (United States)

    Kruyt, Ivo J; Verheul, Jeroen B; Hanssens, Patrick E J; Kunst, Henricus P M

    2018-01-01

    OBJECTIVE Neurofibromatosis Type 2 (NF2) is a tumor syndrome characterized by an autosomal dominant pattern of inheritance. The hallmark of NF2 is the development of bilateral vestibular schwannomas (VSs), generally by 30 years of age. One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2-related VS is still a topic of dispute. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and factors influencing outcome of optimally dosed, contemporary Gamma Knife radiosurgery (GKRS) for growing VSs in patients with NF2 and compare the findings to data obtained in patients with sporadic VS also treated by means of GKRS. METHODS The authors performed a retrospective analysis of 47 growing VSs in 34 NF2 patients who underwent GKRS treatment performed with either the Model C or Perfexion Leksell Gamma Knife, with a median margin dose of 11 Gy. Actuarial tumor control rates were estimated using the Kaplan-Meier method. For patient- and treatment-related factors, a Cox proportional hazards model was used to identify predictors of outcome. Trigeminal, facial, and vestibulocochlear nerve function were assessed before and after treatment. NF2-related VS patients were matched 1:1 with sporadic VS patients who were treated in the same institute, and the same indications for treatment, definitions, and dosimetry were used in order to compare outcomes. RESULTS Actuarial tumor control rates in NF2 patients after 1, 3, 5, and 8 years were 98%, 89%, 87%, and 87%, respectively. Phenotype and tumor volume had significant hazard rates of 0.086 and 22.99, respectively, showing that Feiling-Gardner phenotype and a tumor volume not exceeding 6 cm 3 both were associated with significantly better outcome. Actuarial rates of serviceable hearing preservation after 1, 3, 5, and 7 years were 95%, 82%, 59%, and 33%, respectively. None of the patients

  5. West Nile Virus Surveillance in 2013 via Mosquito Screening in Northern Italy and the Influence of Weather on Virus Circulation

    Science.gov (United States)

    Calzolari, Mattia; Pautasso, Alessandra; Montarsi, Fabrizio; Albieri, Alessandro; Bellini, Romeo; Bonilauri, Paolo; Defilippo, Francesco; Lelli, Davide; Moreno, Ana; Chiari, Mario; Tamba, Marco; Zanoni, Mariagrazia; Varisco, Giorgio; Bertolini, Silvia; Modesto, Paola; Radaelli, Maria Cristina; Iulini, Barbara; Prearo, Marino; Ravagnan, Silvia; Cazzin, Stefania; Mulatti, Paolo; Monne, Isabella; Bonfanti, Lebana; Marangon, Stefano; Goffredo, Maria; Savini, Giovanni; Martini, Simone; Mosca, Andrea; Farioli, Marco; Gemma Brenzoni, Laura; Palei, Manlio; Russo, Francesca; Natalini, Silvano; Angelini, Paola; Casalone, Cristina; Dottori, Michele; Capelli, Gioia

    2015-01-01

    West Nile virus (WNV) is a recently re-emerged health problem in Europe. In Italy, an increasing number of outbreaks of West Nile disease, with occurrences of human cases, have been reported since 2008. This is particularly true in northern Italy, where entomological surveillance systems have been implemented at a regional level. The aim of this study was to use, for the first time, all the entomological data collected in the five regions undergoing surveillance for WNV in northern Italy to characterize the viral circulation (at a spatial and temporal scale), identify potential mosquito vectors, and specify relationships between virus circulation and meteorological conditions. In 2013, 286 sites covering the entire Pianura Padana area were monitored. A total of 757,461 mosquitoes were sampled. Of these, 562,079 were tested by real-time PCR in 9,268 pools, of which 180 (1.9%) were positive for WNV. The largest part of the detected WNV sequences belonged to lineage II, demonstrating that, unlike those in the past, the 2013 outbreak was mainly sustained by this WNV lineage. This surveillance also detected the Usutu virus, a WNV-related flavivirus, in 241 (2.6%) pools. The WNV surveillance systems precisely identified the area affected by the virus and detected the viral circulation approximately two weeks before the occurrence of onset of human cases. Ninety percent of the sampled mosquitoes were Culex pipiens, and 178/180 WNV-positive pools were composed of only this species, suggesting this mosquito is the main WNV vector in northern Italy. A significantly higher abundance of the vector was recorded in the WNV circulation area, which was characterized by warmer and less rainy conditions and greater evapotranspiration compared to the rest of the Pianura Padana, suggesting that areas exposed to these conditions are more suitable for WNV circulation. This observation highlights warmer and less rainy conditions as factors able to enhance WNV circulation and cause virus

  6. West Nile Virus Surveillance in 2013 via Mosquito Screening in Northern Italy and the Influence of Weather on Virus Circulation.

    Directory of Open Access Journals (Sweden)

    Mattia Calzolari

    Full Text Available West Nile virus (WNV is a recently re-emerged health problem in Europe. In Italy, an increasing number of outbreaks of West Nile disease, with occurrences of human cases, have been reported since 2008. This is particularly true in northern Italy, where entomological surveillance systems have been implemented at a regional level. The aim of this study was to use, for the first time, all the entomological data collected in the five regions undergoing surveillance for WNV in northern Italy to characterize the viral circulation (at a spatial and temporal scale, identify potential mosquito vectors, and specify relationships between virus circulation and meteorological conditions. In 2013, 286 sites covering the entire Pianura Padana area were monitored. A total of 757,461 mosquitoes were sampled. Of these, 562,079 were tested by real-time PCR in 9,268 pools, of which 180 (1.9% were positive for WNV. The largest part of the detected WNV sequences belonged to lineage II, demonstrating that, unlike those in the past, the 2013 outbreak was mainly sustained by this WNV lineage. This surveillance also detected the Usutu virus, a WNV-related flavivirus, in 241 (2.6% pools. The WNV surveillance systems precisely identified the area affected by the virus and detected the viral circulation approximately two weeks before the occurrence of onset of human cases. Ninety percent of the sampled mosquitoes were Culex pipiens, and 178/180 WNV-positive pools were composed of only this species, suggesting this mosquito is the main WNV vector in northern Italy. A significantly higher abundance of the vector was recorded in the WNV circulation area, which was characterized by warmer and less rainy conditions and greater evapotranspiration compared to the rest of the Pianura Padana, suggesting that areas exposed to these conditions are more suitable for WNV circulation. This observation highlights warmer and less rainy conditions as factors able to enhance WNV circulation

  7. West Nile Virus: Seroprevalence in Animals in Palestine and Israel.

    Science.gov (United States)

    Azmi, Kifaya; Tirosh-Levy, Sharon; Manasrah, Mu'taz; Mizrahi, Rotem; Nasereddin, Abed; Al-Jawabreh, Amer; Ereqat, Suheir; Abdeen, Ziad; Lustig, Yaniv; Gelman, Boris; Schvartz, Gili; Steinman, Amir

    2017-08-01

    West Nile virus (WNV) epidemiological situation in Israel and Palestine, due to their unique location, draws attention following to the global spread of West Nile fever (WNF). Although much information is available from Israel on clinical cases and prevalence of WNV, clinical cases are rarely reported in Palestine, and prevalence is not known. The objectives of this study were to determine WNV seroprevalence in various domestic animals in Palestine and to reevaluate current seroprevalence, force of infection, and risk factors for WNV exposure in horses in Israel. Sera samples were collected from 717 animals from Palestine and Israel (460 horses, 124 donkeys, 3 mules, 50 goats, 45 sheep, and 35 camels). Two hundred and ten horses were sampled twice. The level of WNV antibodies was determined using commercial Enzyme-linked Immunosorbent Assay (ELISA) Kit. Seroprevalence in equids was 73%. Seroprevalence in Israel (84.6%) was significantly higher than in Palestine (48.6%). Seroprevalence in horses (82.6%) was significantly higher than in donkeys and mules (39.3%). Multivariable statistical analysis showed that geographical area, landscape features (altitude), environmental factors (land surface temperature during the day [LSTD]), species, and age significantly influenced WNV seroprevalence. Fourteen of 95 (14.7%) sheep and goats and 14/35 camels (40%) sampled in Palestine were seropositive for WNV. Of the horses that were sampled twice, 82.8% were seropositive for WNV at the first sampling, and all remained seropositive. Three of the seronegative horses, all from Palestine, converted to positive when resampled (8.5%). The results indicate that domestic animals in Palestine were infected with WNV in the past, and the seroconversion indicates that WNV was circulating in Palestine in the summer of 2014. Control measures to prevent human infection should be implemented in Palestine. Anti WNV antibodies in domestic animals suggest that those species can be used as

  8. First detection of West Nile virus in domestic pigeon in Korea.

    Science.gov (United States)

    Kim, C-Yoon; Oh, Hanseul; Song, Juha; Hur, Moonsuk; Suh, Jae-Hwa; Jheong, Weon-Hwa; Kim, Jong-Taek; Oh, Hong-Shik; Park, Jae-Hak

    2016-12-30

    West Nile virus (WNV) is a mosquito-borne zoonotic pathogen that has spread throughout Europe and the United States. Recently, WNV spread to East and Southeast Asia, and great efforts have been made in South Korea to prevent the spread of WNV from neighboring countries. In this study, we diagnosed the first case of WNV in pigeons ( Columba livia domestica ) residing in cities using a competitive enzyme-linked immunosorbent assay and confirmed it with nested reverse transcription polymerase chain reaction analysis and sequencing. This is the first report to provide convincing evidence that WNV is present within South Korea.

  9. ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

    DEFF Research Database (Denmark)

    Bueno, R C; Canevari, R A; Villacis, R A R

    2014-01-01

    BACKGROUND: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear. PATIENTS AND METHODS: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p...... and miR-18a) expression levels were evaluated by quantitative real-time PCR (RT-qPCR) in 52 BC and 3 normal breast samples. ATM protein expression was assessed by immunohistochemistry in 968 BC and 35 adjacent normal breast tissues. ATM copy number alteration was detected by array comparative genomic...... hybridization (aCGH) in 42 tumours. RESULTS: Low ATM levels were associated with tumour grade. Absence of ATM protein expression was associated with distant metastasis (P ATM...

  10. Severe neuroinvasive West Nile virus infection in a child with undiagnosed Addison's disease

    Directory of Open Access Journals (Sweden)

    Kevin Messacar

    2014-01-01

    Full Text Available This report describes a case of West Nile virus (WNV meningoencephalitis in a child who presented with fever, headache, seizures, and altered mental status, as well as hyponatremia and bronzing of the skin. Findings that led to the diagnosis of WNV included plasma-cell pleocytosis of the cerebrospinal fluid (CSF and linear chorioretinitis on ophthalmologic exam. The diagnosis was confirmed by a positive serum and CSF WNV IgM. The acute WNV infection triggered an adrenal crisis which uncovered a new diagnosis of underlying Addison's disease. This is the first case report of severe neuroinvasive WNV disease in a pediatric patient with primary adrenal insufficiency. Neuroinvasive WNV disease is uncommon in children, but may have a more severe presentation in those with certain underlying medical conditions.

  11. Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning

    International Nuclear Information System (INIS)

    Takahashi, Hirohide; Snow, B.J.; Bhatt, M.H.; Peppard, R.; Eisen, A.; Calne, D.B.

    1993-01-01

    Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, the authors did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. They found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis, and, perhaps, etiology

  12. DNA-methyltransferase 3B 39179 G > T polymorphism and risk of sporadic colorectal cancer in a subset of Iranian population

    Directory of Open Access Journals (Sweden)

    Abdolreza Daraei

    2011-01-01

    Full Text Available Background: Epigenetic event is a biological regulation that influences the expression of various genes involved in cancer. DNA methylation is established by DNA methyltransferases, particularly DNAmethyltransferase 3B (DNMT3B. It seems to play an oncogenic role in the creation of abnormal methylation during tumorigenesis. The polymorphisms of the DNMT3B gene may influence DNMT3B activity in DNA methylation and increase the susceptibility to several cancers. These genetic polymorphisms have been studied in several cancers in different populations. Methods: In this study, we performed a case-control study with 125 colorectal cancer patients and 135 cancer-free controls to evaluate the association between DNMT3B G39179T polymorphism (rs1569686 in the promoter region and the risk of sporadic colorectal cancer. Up to now, few studies have investigated the role of this gene variant in sporadic colorectal cancer with no familial history. The genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. Results: We found that compared with G allele carriers, statistically the DNMT3B TT genotype (%34 was significantly associated with increased risk of colorectal cancer (adjusted OR, 3.993, 95% CI, 1.726-9.238, P = 0.001. Compared with DNMT3B TT genotype, the GT and GG genotypes had lower risk of developing sporadic colorectal cancer (OR = 0.848, 95% CI = 0.436-1.650. Conclusions: Our findings were consistent with that of previously reported case-control studies with colorectal cancer. These results suggest that the DNMT3B G39179T polymorphism influences DNMT3B expression, thus contributing to the genetic susceptibility to colorectal cancer. Further mechanistic studies are needed to unravel the causal molecular mechanisms.

  13. Sporadic colorectal cancer and individual susceptibility: A review of the association studies investigating the role of DNA repair genetic polymorphisms

    Czech Academy of Sciences Publication Activity Database

    Naccarati, Alessio; Pardini, B.; Hemminki, K.; Vodička, Pavel

    2007-01-01

    Roč. 635, 2-3(2007), s.118-145 ISSN 1383-5742 R&D Projects: GA MZd NR8563; GA ČR GA310/05/2626 Institutional research plan: CEZ:AV0Z50390512 Keywords : Sporadic colorectal cancer * Individual susceptibility * DNA repair Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.353, year: 2007

  14. Long-term Auditory Symptoms in Patients With Sporadic Vestibular Schwannoma: An International Cross-Sectional Study.

    Science.gov (United States)

    Tveiten, Oystein Vesterli; Carlson, Matthew L; Goplen, Frederik; Vassbotn, Flemming; Link, Michael J; Lund-Johansen, Morten

    2015-08-01

    There are limited data on the long-term auditory symptoms in patients with sporadic small- and medium-sized vestibular schwannoma (VS). The initial treatment strategy for VS is controversial. To characterize auditory symptoms in a large cohort of patients with VS. Patients with ≤3 cm VS who underwent primary microsurgery, gamma knife surgery, or observation between 1998 and 2008 at 2 independent hospitals were identified. Clinical data were extracted from existing VS databases. At a mean time of 7.7 years after initial treatment, patients were surveyed via mail with the use of the Hearing Handicap Inventory for Adults (HHIA) and the Tinnitus Handicap Inventory. The response rate was 79%; a total of 539 respondents were analyzed. Overall, the hearing prognosis was poor, because more than 75% of all patients had nonserviceable hearing at the last clinical follow-up. Good baseline hearing proved to be a strong predictor for maintained serviceable hearing. Treatment modality was independently associated with both audiometric outcome and HHIA results. Active treatment with microsurgery or gamma knife surgery did not appear to be protective, because patients who were observed had the greatest probability of durable hearing. Patients in the surgical series had the greatest hearing loss. Tinnitus Handicap Inventory results were less predictable. The only predictors of tinnitus handicap were age and HHIA score. The overall prognosis for hearing in sporadic VS is poor regardless of treatment strategy. Treatment modality was an independent predictor of hearing status; observation was associated with the highest rate of hearing preservation. .

  15. Summary and consensus in 7th International Conference on acoustic neuroma: An update for the management of sporadic acoustic neuromas

    Directory of Open Access Journals (Sweden)

    Hao Wu

    2016-12-01

    Full Text Available Sporadic vestibular schwannoma (acoustic neuroma is a benign tumor arising from cochleovestibular nerve. Nowadays, various specialties and medical centers are treating this disease, and the multidisciplinary collaboration is the trend. In an effort to promote a uniform standard for reporting clinical results, even for treatment indications, the mainly controversies were posed and discussed during the 7th International Conference on acoustic neuroma, and the agreement was summarized by the Committee of this conference. The main symptoms grading and tumor stage should note its name of classification for making them comparable. The goal of the modern managements for vestibular schwannoma is to improve the quality of life with lower mortality, lower morbidity and better neurological function preservation. The experience of surgical team and their preference might be a major factor for the outcome. Because of lacking of long-term follow-up large data after radiotherapy, and with the development of microsurgery, radiotherapy is now less recommended except for recurrent cases or elderly patients. Keywords: Sporadic acoustic neuroma, Vestibular schwannoma, Management, Symptoms grading, Tumor stage, Microsurgery, Radiotherapy

  16. Solar eclipse effects of 22 July 2009 on Sporadic-E

    Directory of Open Access Journals (Sweden)

    G. Chen

    2010-02-01

    Full Text Available The total solar eclipse of 22 July 2009, was visible from some regions of China and the intense sporadic-E (Es that broke out during the solar eclipse period over the eastern China provided a unique chance to study solar eclipse effects on the Es-layer. The ground based high-frequency (HF vertical-incidence and oblique-incidence backscatter radio systems in Wuhan and an HF oblique receivers located in Suzhou were operated to detect the Es-layer. The vertical, oblique and backscatter ionograms of 22 and 23 July were recorded, processed and analyzed. The analyzing results show that the critical frequency of Es, the hop number and power of the rays transmitted from Wuhan to Suzhou as well as the Doppler frequency shift of the one-hop oblique-incidence waves reflected by the Es-layer all increased during the solar eclipse period. These variations are displayed in the paper and explained to be induced by the wind-field, which is produced by the powerful meridional air flows from the sunshine region to the moon's shadow.

  17. Solar eclipse effects of 22 July 2009 on Sporadic-E

    Directory of Open Access Journals (Sweden)

    G. Chen

    2010-02-01

    Full Text Available The total solar eclipse of 22 July 2009, was visible from some regions of China and the intense sporadic-E (Es that broke out during the solar eclipse period over the eastern China provided a unique chance to study solar eclipse effects on the Es-layer. The ground based high-frequency (HF vertical-incidence and oblique-incidence backscatter radio systems in Wuhan and an HF oblique receivers located in Suzhou were operated to detect the Es-layer. The vertical, oblique and backscatter ionograms of 22 and 23 July were recorded, processed and analyzed. The analyzing results show that the critical frequency of Es, the hop number and power of the rays transmitted from Wuhan to Suzhou as well as the Doppler frequency shift of the one-hop oblique-incidence waves reflected by the Es-layer all increased during the solar eclipse period. These variations are displayed in the paper and explained to be induced by the wind-field, which is produced by the powerful meridional air flows from the sunshine region to the moon's shadow.

  18. The Immune Responses of the Animal Hosts of West Nile Virus: A Comparison of Insects, Birds, and Mammals

    Directory of Open Access Journals (Sweden)

    Laura R. H. Ahlers

    2018-04-01

    Full Text Available Vector-borne diseases, including arboviruses, pose a serious threat to public health worldwide. Arboviruses of the flavivirus genus, such as Zika virus (ZIKV, dengue virus, yellow fever virus (YFV, and West Nile virus (WNV, are transmitted to humans from insect vectors and can cause serious disease. In 2017, over 2,000 reported cases of WNV virus infection occurred in the United States, with two-thirds of cases classified as neuroinvasive. WNV transmission cycles through two different animal populations: birds and mosquitoes. Mammals, particularly humans and horses, can become infected through mosquito bites and represent dead-end hosts of WNV infection. Because WNV can infect diverse species, research on this arbovirus has investigated the host response in mosquitoes, birds, humans, and horses. With the growing geographical range of the WNV mosquito vector and increased human exposure, improved surveillance and treatment of the infection will enhance public health in areas where WNV is endemic. In this review, we survey the bionomics of mosquito species involved in Nearctic WNV transmission. Subsequently, we describe the known immune response pathways that counter WNV infection in insects, birds, and mammals, as well as the mechanisms known to curb viral infection. Moreover, we discuss the bacterium Wolbachia and its involvement in reducing flavivirus titer in insects. Finally, we highlight the similarities of the known immune pathways and identify potential targets for future studies aimed at improving antiviral therapeutic and vaccination design.

  19. Epitope-blocking enzyme-linked immunosorbent assay to differentiate west nile virus from Japanese encephalitis virus infections in equine sera.

    Science.gov (United States)

    Kitai, Yoko; Shoda, Mizue; Kondo, Takashi; Konishi, Eiji

    2007-08-01

    West Nile virus (WNV) is now widely distributed worldwide, except in most areas of Asia where Japanese encephalitis virus (JEV) is distributed. Considering the movement and migration of reservoir birds, there is concern that WNV may be introduced in Asian countries. Although manuals and guidelines for serological tests have been created in Japan in preparedness for the introduction of WNV, differential diagnosis between WNV and JEV may be complicated by antigenic cross-reactivities between these flaviviruses. Here, we generated a monoclonal antibody specific for the nonstructural protein 1 (NS1) of WNV and established an epitope-blocking enzyme-linked immunosorbent assay that can differentiate WNV from JEV infections in horse sera. Under conditions well suited for our assay system, samples collected from 95 horses in Japan (regarded as negative for WNV antibodies), including those collected from horses naturally infected with JEV, showed a mean inhibition value of 8.2% and a standard deviation (SD) of 6.5%. However, inhibition values obtained with serum used as a positive control (obtained after 28 days from a horse experimentally infected with WNV) in nine separate experiments showed a mean of 54.4% and an SD of 7.1%. We tentatively determined 27.6% (mean + 3 x SD obtained with 95 negative samples) as the cutoff value to differentiate positive from negative samples. Under this criterion, two horses experimentally infected with WNV were diagnosed as positive at 12 and 14 days, respectively, after infection.

  20. Detection of West Nile virus-specific antibodies and nucleic acid in horses and mosquitoes, respectively, in Nuevo Leon State, northern Mexico, 2006-2007.

    Science.gov (United States)

    Ibarra-Juarez, L; Eisen, L; Bolling, B G; Beaty, B J; Blitvich, B J; Sanchez-Casas, R M; Ayala-Sulca, Y O; Fernandez-Salas, I

    2012-09-01

    In the last 5 years, there has been only one reported human case of West Nile virus (WNV) disease in northern Mexico. To determine if the virus was still circulating in this region, equine and entomological surveillance for WNV was conducted in the state of Nuevo Leon in northern Mexico in 2006 and 2007. A total of 203 horses were serologically assayed for antibodies to WNV using an epitope-blocking enzyme-linked immunosorbent assay (bELISA). Seroprevalences for WNV in horses sampled in 2006 and 2007 were 26% and 45%, respectively. Mosquito collections in 2007 produced 7365 specimens representing 15 species. Culex mosquitoes were screened for WNV RNA and other genera (Mansonia, Anopheles, Aedes, Psorophora and Uranotaenia) were screened for flaviviruses using reverse-transcription (RT)-PCR. Two pools consisting of Culex spp. mosquitoes contained WNV RNA. Molecular species identification revealed that neither pool included Culex quinquefasciatus (Say) (Diptera:Culicidae) complex mosquitoes. No evidence of flaviviruses was found in the other mosquito genera examined. These data provide evidence that WNV is currently circulating in northern Mexico and that non-Cx. quinquefasciatus spp. mosquitoes may be participating in the WNV transmission cycle in this region. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  1. Large Human Outbreak of West Nile Virus Infection in North-Eastern Italy in 2012

    Directory of Open Access Journals (Sweden)

    Luisa Barzon

    2013-11-01

    Full Text Available Human cases of West Nile virus (WNV disease have been reported in Italy since 2008. So far, most cases have been identified in north-eastern Italy, where, in 2012, the largest outbreak of WNV infection ever recorded in Italy occurred. Most cases of the 2012 outbreak were identified in the Veneto region, where a special surveillance plan for West Nile fever was in place. In this outbreak, 25 cases of West Nile neuroinvasive disease and 17 cases of fever were confirmed. In addition, 14 WNV RNA-positive blood donors were identified by screening of blood and organ donations and two cases of asymptomatic infection were diagnosed by active surveillance of subjects at risk of WNV exposure. Two cases of death due to WNND were reported. Molecular testing demonstrated the presence of WNV lineage 1 in all WNV RNA-positive patients and, in 15 cases, infection by the novel Livenza strain was ascertained. Surveillance in other Italian regions notified one case of neuroinvasive disease in the south of Italy and two cases in Sardinia. Integrated surveillance for WNV infection remains a public health priority in Italy and vector control activities have been strengthened in areas of WNV circulation.

  2. Host genetic risk factors for West Nile virus infection and disease progression.

    Directory of Open Access Journals (Sweden)

    Abigail W Bigham

    Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

  3. Congenital terminal transverse deformity of upper limb: clinical and radiological findings in a sporadic care.

    Science.gov (United States)

    Malik, Sajid; Afzal, Muhammad

    2013-03-01

    Congenital transverse limb anomalies are rare, which affect upper and/or lower limbs and may accompany several syndromic malformations. We present a sporadic male subject with congenital, unilateral transverse arrest of the left hand. The affected arm was observed to be short with reduced zeugopod and truncated palm. Fingers were represented by five bead-like nubbins. Roentgenographic examination revealed short radius and ulna with hypoplastic distal heads, absent carpals/metacarpals, and a hypoplastic bony island in each nubbin. Consanguinity was denied, and the subject had no symptoms in the orofacial, neurological and skeletal systems. Detailed clinical data with literature survey is presented.

  4. Sporadic case of listeriosis associated with the consumption of a Listeria monocytogenes-contaminated 'Camembert' cheese.

    Science.gov (United States)

    Gilot, P; Hermans, C; Yde, M; Gigi, J; Janssens, M; Genicot, A; André, P; Wauters, G

    1997-09-01

    Listeria monocytogenes is an intracellular gram-positive organism responsible for severe infections in both humans and animals. Whereas the food-borne transmission of listeriosis was demonstrated in several outbreaks, most cases of listeriosis occur sporadically and are rarely linked with consumption of contaminated foods. In this paper a case of septicaemia with L. monocytogenes in a 73-year-old immunocompromised man is described. Evidence for the association of this case of listeriosis with the consumption of a contaminated 'Camembert' cheese is provided by serotyping, esterase typing, DNA macrorestriction patterns analysis and level of virulence of the isolated strains for mice.

  5. Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

    NARCIS (Netherlands)

    Parchi, P.; Strammiello, R.; Notari, S.; Giese, A.; Langeveld, J.P.M.; Ladogana, A.; Zerr, I.; Roncaroli, F.; Cras, P.; Ghetti, B.; Pocchiari, M.; Kretzschmar, H.; Capellari, S.

    2009-01-01

    Six subtypes of sporadic Creutzfeldt-Jakob disease with distinctive clinico-pathological features have been identified largely based on two types of the abnormal prion protein, PrPSc, and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects

  6. Screening for sporadic or familial medullary thyroid carcinoma. Scintiscan s and radio-immunotherapy

    International Nuclear Information System (INIS)

    Rhmer, V.; Murat, A.

    2000-01-01

    The screening for sporadic medullary thyroid carcinoma relies upon calcitoninemia level, basal or during pentagastrine stimulation test. MEN2 are associated with nearly the third of medullary thyroid carcinoma. In these cases, prognosis of thyroid carcinoma is mainly driven by the tumor status at the time of surgery. Up to date, diagnosis relies upon the genetic screening. Prophylactic thyroidectomy indication may take account of calcitoninemia. Most of the molecules that have been suggested for scintiscan lack of accuracy and large use cannot be recommended. Promising results have been obtained with monoclonal antibodies anti-CEA, particularly with dual targeting antiCEA antiDTPA. This last technique may also be used for radio-guided surgery. Its use for radio-immunotherapy is under investigation. (authors)

  7. SEROLOGIC EVIDENCE OF WEST NILE VIRUS INFECTION IN BIRDS, TAMAULIPAS STATE, MEXICO

    OpenAIRE

    beaty, barry; FERNANDEZ, ILDEFONSO; contreras, juan francisco; blitvich, bradley; gonzalez, jose ignacio; cavazos, amanda a; loroño, maria alba; gluber, duante j.; Cropp, bruce; Calisher , Charles

    2003-01-01

    Following the introduction of West Nile virus (WNV) into North America in 1999, surveillance for WNV in migratory and resident birds was established in Tamaulipas State, northern Mexico in December 2001. Overall, 796 birds representing 70 species and 10 orders were captured and assayed for antibodies to WNV. Nine birds had flavivirus-specific antibodies by epitope-blocking enzyme-linked immunosorbent assay; four were confirmed to have antibody to WNV by plaque reduction neutralization test. T...

  8. Sporadic Legionnaires' disease: the role of domestic electric hot-water tanks.

    Science.gov (United States)

    Dufresne, S F; Locas, M C; Duchesne, A; Restieri, C; Ismaïl, J; Lefebvre, B; Labbé, A C; Dion, R; Plante, M; Laverdière, M

    2012-01-01

    Sporadic community-acquired legionellosis (SCAL) can be acquired through contaminated aerosols from residential potable water. Electricity-dependent hot-water tanks are widely used in the province of Quebec (Canada) and have been shown to be frequently contaminated with Legionella spp. We prospectively investigated the homes of culture-proven SCAL patients from Quebec in order to establish the proportion of patients whose domestic potable hot-water system was contaminated with the same Legionella isolate that caused their pneumonia. Water samples were collected in each patient's home. Environmental and clinical isolates were compared using pulsed-field gel electrophoresis. Thirty-six patients were enrolled into the study. Legionella was recovered in 12/36 (33%) homes. The residential and clinical isolates were found to be microbiologically related in 5/36 (14%) patients. Contaminated electricity-heated domestic hot-water systems contribute to the acquisition of SCAL. The proportion is similar to previous reports, but may be underestimated.

  9. Insulin-Resistant Brain State: the culprit in sporadic Alzheimer’s Disease?

    Science.gov (United States)

    Correia, Sónia C.; Santos, Renato X.; Perry, George; Zhu, Xiongwei; Moreira, Paula I.; Smith, Mark A.

    2011-01-01

    Severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer’s disease (sAD) pathology. Indeed, the “insulin-resistant brain state” has been hypothesized to form the core of the neurodegenerative events that occur in sAD. In this vein, intracerebroventricular administration of subdiabetogenic doses of streptozotocin (STZ) in rats can induce an insulin-resistant brain state, which is proposed as a suitable experimental model of sAD. This review highlights the involvement of disturbed brain insulin metabolism in sAD etiopathogenesis. Furthermore, current knowledge demonstrates that central STZ administration produces brain pathology and behavioral changes that resemble changes found in sAD patients. The STZ-intracerebroventricularly treated rat represents a promising experimental tool in this field by providing new insights concerning early brain alterations in sAD, which can be translated in novel etiopathogenic and therapeutic approaches in this disease. PMID:21262392

  10. Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism.

    Science.gov (United States)

    Roberts, Stephanie A; Moon, Jennifer E; Dauber, Andrew; Smith, Jessica R

    2017-03-01

    Primary nonautoimmune hyperthyroidism is a rare cause of neonatal hyperthyroidism. This results from an activating mutation in the thyrotropin-receptor (TSHR). It can be inherited in an autosomal dominant manner or occur sporadically as a de novo mutation. Affected individuals display a wide phenotype from severe neonatal to mild subclinical hyperthyroidism. We describe a 6-month-old boy with a de novo mutation in the TSHR gene who presented with accelerated growth, enlarging head circumference, tremor and thyrotoxicosis. Genomic DNA from the patient's and parents' peripheral blood leukocytes was extracted. Exons 9 and 10 of the TSHR gene were amplified by PCR and sequenced. Sequencing exon 10 of the TSHR gene revealed a novel heterozygous missense mutation substituting cytosine to adenine at nucleotide position 1534 in the patient's peripheral blood leukocytes. This leads to a substitution of leucine to methionine at amino acid position 512. The mutation was absent in the parents. In silico modeling by PolyPhen-2 and SIFT predicted the mutation to be deleterious. The p.Leu512Met mutation (c.1534C>A) of the TSHR gene has not been previously described in germline or somatic mutations. This case presentation highlights the possibility of mild thyrotoxicosis in affected individuals and contributes to the understanding of sporadic non-autoimmune primary hyperthyroidism.

  11. Association study between XRCC1 gene polymorphisms and sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Coppedè, Fabio; Migheli, Francesca; Lo Gerfo, Annalisa; Fabbrizi, Maria Rita; Carlesi, Cecilia; Mancuso, Michelangelo; Corti, Stefania; Mezzina, Nicoletta; del Bo, Roberto; Comi, Giacomo P; Siciliano, Gabriele; Migliore, Lucia

    2010-01-01

    The aim of the present study was to investigate the possible contribution of three common functional polymorphisms in the DNA repair protein X-ray repair cross-complementing group 1 (XRCC1), namely Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487), to sporadic amyotrophic lateral sclerosis (SALS). We genotyped 206 Italian SALS patients and 203 matched controls for XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms by means of PCR/RFLP technique, searching for association between any of the studied polymorphisms and disease risk, age and site of onset. We observed a statistically significant difference in XRCC1 Gln399 allele frequencies between SALS cases and controls (0.39/0.28; p=0.001). The present study suggests that the XRCC1 Arg399Gln polymorphism might contribute to SALS risk.

  12. Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection.

    Science.gov (United States)

    Quick, Eamon D; Seitz, Scott; Clarke, Penny; Tyler, Kenneth L

    2017-11-15

    West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized ex vivo spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in ex vivo CNS tissue. IMPORTANCE West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments available

  13. Simultaneous lidar observation of peculiar sporadic K and Na layers at São José dos Campos (23.1°S, 45.9°W), Brazil

    Science.gov (United States)

    Jiao, Jing; Yang, Guotao; Cheng, Xuewu; Liu, Zhengkuan; Wang, Jihong; Yan, Zhenzhong; Wang, Chi; Batista, Paulo; Pimenta, Alexandre; Andrioli, Vânia; Denardini, C. M.

    2018-04-01

    We present the first simultaneous observation of mesopause sodium (Na) and potassium (K) layer by a lidar which has Na and K channel simultaneously at the South Hemisphere site, São José dos Campos (23.1°S, 45.9°W). Measurements reported here were conducted on two nights with 3.5 and 8 h of observations in November 2016. On 20 November 2016, sporadic layers in both Na and K layer occurred above 100 km, and the higher layers corresponded well with sporadic E (Es) layer. And the density of Na at 100-105 km is higher than that at main layer around 90 km, but K density around 100 km is at least 3 times smaller compared with the K density around 90 km for the similar period. On 21 November 2016, both sporadic layers occurred in main layer height with obvious descending variations with time, which seems like tidal induced. Notably, the peak K/Na ratio slowly increased with time. And Na layer and K layer showed different processes along with time with K density reaching its maximum 1 h later than that of Na. Correlations of Na/K density, Es, and winds were also discussed.

  14. Seria o vírus do Oeste do Nilo causa potencial de infecção no sistema nervoso central no Brasil?

    OpenAIRE

    Soares, Cristiane N; Castro, Mauro J. Cabral; Peralta, José M; Freitas, Marcos R.G. de; Puccioni-Sohler, Marzia

    2010-01-01

    Meningitis and encephalitis are complications of West Nile virus (WNV) infection. Although WNV is endemic in North America, the virus has recently been reported in Colombia and Argentina. Investigation of WNV in Brazil is important since this virus has never been studied previously in this country. OBJECTIVE: To investigate the presence of WNV infection in viral encephalitis/meningitis cases of unknown etiology in the city of Rio de Janeiro, Brazil. METHOD: Thirty-seven adults with viral meni...

  15. Use of Temperature to Improve West Nile Virus Forecasts

    Science.gov (United States)

    Shaman, J. L.; DeFelice, N.; Schneider, Z.; Little, E.; Barker, C.; Caillouet, K.; Campbell, S.; Damian, D.; Irwin, P.; Jones, H.; Townsend, J.

    2017-12-01

    Ecological and laboratory studies have demonstrated that temperature modulates West Nile virus (WNV) transmission dynamics and spillover infection to humans. Here we explore whether the inclusion of temperature forcing in a model depicting WNV transmission improves WNV forecast accuracy relative to a baseline model depicting WNV transmission without temperature forcing. Both models are optimized using a data assimilation method and two observed data streams: mosquito infection rates and reported human WNV cases. Each coupled model-inference framework is then used to generate retrospective ensemble forecasts of WNV for 110 outbreak years from among 12 geographically diverse United States counties. The temperature-forced model improves forecast accuracy for much of the outbreak season. From the end of July until the beginning of October, a timespan during which 70% of human cases are reported, the temperature-forced model generated forecasts of the total number of human cases over the next 3 weeks, total number of human cases over the season, the week with the highest percentage of infectious mosquitoes, and the peak percentage of infectious mosquitoes that were on average 5%, 10%, 12%, and 6% more accurate, respectively, than the baseline model. These results indicate that use of temperature forcing improves WNV forecast accuracy and provide further evidence that temperatures influence rates of WNV transmission. The findings help build a foundation for implementation of a statistically rigorous system for real-time forecast of seasonal WNV outbreaks and their use as a quantitative decision support tool for public health officials and mosquito control programs.

  16. Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge.

    Science.gov (United States)

    Gershoni-Yahalom, Orly; Landes, Shimon; Kleiman-Shoval, Smadar; Ben-Nathan, David; Kam, Michal; Lachmi, Bat-El; Khinich, Yevgeny; Simanov, Michael; Samina, Itzhak; Eitan, Anat; Cohen, Irun R; Rager-Zisman, Bracha; Porgador, Angel

    2010-08-01

    The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-gammain vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV.

  17. Sentinel site-enhanced near-real time surveillance documenting West Nile virus circulation in two Culex mosquito species indicating different transmission characteristics, Djibouti City, Djibouti.

    Science.gov (United States)

    Faulde, Michael K; Spiesberger, Michael; Abbas, Babiker

    2012-08-01

    The Horn of Africa represents a region formerly known to be highly susceptible to mosquito-borne infectious diseases. In order to investigate whether autochthonous WNV transmission occurs in the Djibouti City area, in how far, and which of, the endemic Culex mosquito species are involved in WNV circulation activity,and whether sentinel site-enhanced near-real time surveillance (SSE-NRTS) may increase WNV detection sensitivity, mosquito vector monitoring was conducted from January 2010 to June 2012. Six monitoring locations, including two identified sentinel sites, considered most probable for potential anthroponotic and zoonotic virus circulation activity, have been continuously employed. Among the 20431 mosquitoes collected, 19069 (93.4%) were Cx. quinquefasciatus, and 1345 (6.6%) Cx. pipiens ssp. torridus. WNV lineage 2 circulation activity was detected between December 20th, 2010 and January 7th, 2011. Overall, 19 WNV RNA-positive mosquito pools were detected. Generally, urban environment-specific WNV-RNA circulation took place in Cx. pipiens ssp. torridus, whereas periurban and rural area-linked circulation was detected only in Cx. quinquefasciatus. Serological investigation data from 10 volunteers employed at the dislocated zoonotic WNV transmission sentinel site suggest that six persons (60%) had an acute, or recent, WNV infection. Results show that WNV should be considered endemic for Djibouti and sentinel site-enhanced near-real time surveillance is an elegant and highly effective epidemiological tool. In Djibouti, the endemicity level, public health impact and transmission modes of vector-borne diseases in concordance with locally optimized monitoring and control regimen deserve further investigation.

  18. Use of temperature to improve West Nile virus forecasts.

    Directory of Open Access Journals (Sweden)

    Nicholas B DeFelice

    2018-03-01

    Full Text Available Ecological and laboratory studies have demonstrated that temperature modulates West Nile virus (WNV transmission dynamics and spillover infection to humans. Here we explore whether inclusion of temperature forcing in a model depicting WNV transmission improves WNV forecast accuracy relative to a baseline model depicting WNV transmission without temperature forcing. Both models are optimized using a data assimilation method and two observed data streams: mosquito infection rates and reported human WNV cases. Each coupled model-inference framework is then used to generate retrospective ensemble forecasts of WNV for 110 outbreak years from among 12 geographically diverse United States counties. The temperature-forced model improves forecast accuracy for much of the outbreak season. From the end of July until the beginning of October, a timespan during which 70% of human cases are reported, the temperature-forced model generated forecasts of the total number of human cases over the next 3 weeks, total number of human cases over the season, the week with the highest percentage of infectious mosquitoes, and the peak percentage of infectious mosquitoes that on average increased absolute forecast accuracy 5%, 10%, 12%, and 6%, respectively, over the non-temperature forced baseline model. These results indicate that use of temperature forcing improves WNV forecast accuracy and provide further evidence that temperature influences rates of WNV transmission. The findings provide a foundation for implementation of a statistically rigorous system for real-time forecast of seasonal WNV outbreaks and their use as a quantitative decision support tool for public health officials and mosquito control programs.

  19. Association of spring-summer hydrology and meteorology with human West Nile virus infection in West Texas, USA, 2002-2016.

    Science.gov (United States)

    Ukawuba, Israel; Shaman, Jeffrey

    2018-04-04

    The emergence of West Nile virus (WNV) in the Western Hemisphere has motivated research into the processes contributing to the incidence and persistence of the disease in the region. Meteorology and hydrology are fundamental determinants of vector-borne disease transmission dynamics of a region. The availability of water influences the population dynamics of vector and host, while temperature impacts vector growth rates, feeding habits, and disease transmission potential. Characterization of the temporal pattern of environmental factors influencing WNV risk is crucial to broaden our understanding of local transmission dynamics and to inform efforts of control and surveillance. We used hydrologic, meteorological and WNV data from west Texas (2002-2016) to analyze the relationship between environmental conditions and annual human WNV infection. A Bayesian model averaging framework was used to evaluate the association of monthly environmental conditions with WNV infection. Findings indicate that wet conditions in the spring combined with dry and cool conditions in the summer are associated with increased annual WNV cases. Bayesian multi-model inference reveals monthly means of soil moisture, specific humidity and temperature to be the most important variables among predictors tested. Environmental conditions in March, June, July and August were the leading predictors in the best-fitting models. The results significantly link soil moisture and temperature in the spring and summer to WNV transmission risk. Wet spring in association with dry and cool summer was the temporal pattern best-describing WNV, regardless of year. Our findings also highlight that soil moisture may be a stronger predictor of annual WNV transmission than rainfall.

  20. Strong Sporadic E Occurrence Detected by Ground-Based GNSS

    Science.gov (United States)

    Sun, Wenjie; Ning, Baiqi; Yue, Xinan; Li, Guozhu; Hu, Lianhuan; Chang, Shoumin; Lan, Jiaping; Zhu, Zhengping; Zhao, Biqiang; Lin, Jian

    2018-04-01

    The ionospheric sporadic E (Es) layer has significant impact on radio wave propagation. The traditional techniques employed for Es layer observation, for example, ionosondes, are not dense enough to resolve the morphology and dynamics of Es layer in spatial distribution. The ground-based Global Navigation Satellite Systems (GNSS) technique is expected to shed light on the understanding of regional strong Es occurrence, owing to the facts that the critical frequency (foEs) of strong Es structure is usually high enough to cause pulse-like disturbances in GNSS total electron content (TEC), and a large number of GNSS receivers have been deployed all over the world. Based on the Chinese ground-based GNSS networks, including the Crustal Movement Observation Network of China and the Beidou Ionospheric Observation Network, a large-scale strong Es event was observed in the middle latitude of China. The strong Es shown as a band-like structure in the southwest-northeast direction extended more than 1,000 km. By making a comparative analysis of Es occurrences identified from the simultaneous observations by ionosondes and GNSS TEC receivers over China middle latitude statistically, we found that GNSS TEC can be well employed to observe strong Es occurrence with a threshold value of foEs, 14 MHz.

  1. The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein

    Energy Technology Data Exchange (ETDEWEB)

    Hoenen, Antje [School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia); Gillespie, Leah [Department of Microbiology, La Trobe University, Melbourne (Australia); Department of Microbiology and Immunology, University of Melbourne, Melbourne (Australia); Morgan, Garry; Heide, Peter van der [Institute for Molecular Bioscience, University of Queensland, Brisbane (Australia); Khromykh, Alexander [School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia); Australian Infectious Diseases Research Centre, University of Queensland, Brisbane (Australia); Mackenzie, Jason, E-mail: jason.mackenzie@unimelb.edu.au [Department of Microbiology, La Trobe University, Melbourne (Australia); Department of Microbiology and Immunology, University of Melbourne, Melbourne (Australia)

    2014-01-05

    Flaviviruses have evolved means to evade host innate immune responses. Recent evidence suggests this is due to prevention of interferon production and signaling in flavivirus-infected cells. Here we show that the interferon-induced MxA protein can sequester the West Nile virus strain Kunjin virus (WNV{sub KUN}) capsid protein in cytoplasmic tubular structures in an expression-replication system. This sequestering resulted in reduced titers of secreted WNV{sub KUN} particles. We show by electron microscopy, tomography and 3D modeling that these cytoplasmic tubular structures form organized bundles. Additionally we show that recombinant ER-targeted MxA can restrict production of infectious WNV{sub KUN} under conditions of virus infection. Our results indicate a co-ordinated and compartmentalized WNV{sub KUN} assembly process may prevent recognition of viral components by MxA, particularly the capsid protein. This recognition can be exploited if MxA is targeted to intracellular sites of WNV{sub KUN} assembly. This results in further understanding of the mechanisms of flavivirus evasion from the immune system. - Highlights: • We show that the ISG MxA can recognize the West Nile virus capsid protein. • Interaction between WNV C protein and MxA induces cytoplasmic fibrils. • MxA can be retargeted to the ER to restrict WNV particle release. • WNV assembly process is a strategy to avoid MxA recognition.

  2. The evolving genetic risk for sporadic ALS.

    Science.gov (United States)

    Gibson, Summer B; Downie, Jonathan M; Tsetsou, Spyridoula; Feusier, Julie E; Figueroa, Karla P; Bromberg, Mark B; Jorde, Lynn B; Pulst, Stefan M

    2017-07-18

    To estimate the genetic risk conferred by known amyotrophic lateral sclerosis (ALS)-associated genes to the pathogenesis of sporadic ALS (SALS) using variant allele frequencies combined with predicted variant pathogenicity. Whole exome sequencing and repeat expansion PCR of C9orf72 and ATXN2 were performed on 87 patients of European ancestry with SALS seen at the University of Utah. DNA variants that change the protein coding sequence of 31 ALS-associated genes were annotated to determine which were rare and deleterious as predicted by MetaSVM. The percentage of patients with SALS with a rare and deleterious variant or repeat expansion in an ALS-associated gene was calculated. An odds ratio analysis was performed comparing the burden of ALS-associated genes in patients with SALS vs 324 normal controls. Nineteen rare nonsynonymous variants in an ALS-associated gene, 2 of which were found in 2 different individuals, were identified in 21 patients with SALS. Further, 5 deleterious C9orf72 and 2 ATXN2 repeat expansions were identified. A total of 17.2% of patients with SALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene. The genetic burden of ALS-associated genes in patients with SALS as predicted by MetaSVM was significantly higher than in normal controls. Previous analyses have identified SALS-predisposing variants only in terms of their rarity in normal control populations. By incorporating variant pathogenicity as well as variant frequency, we demonstrated that the genetic risk contributed by these genes for SALS is substantially lower than previous estimates. © 2017 American Academy of Neurology.

  3. The human homologue of unc-93 maps to chromosome 6q27 - characterisation and analysis in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Liu, Ying; Dodds, Phillippa; Emilion, Gracy

    2002-01-01

    In sporadic ovarian cancer, we have previously reported allele loss at D6S193 (62%) on chromosome 6q27, which suggested the presence of a putative tumour suppressor gene. Based on our data and that from another group, the minimal region of allele loss was between D6S264 and D6S149 (7.4 cM). To id...

  4. The influence of sporadic anovulation on hormone levels in ovulatory cycles

    Science.gov (United States)

    Hambridge, H.L.; Mumford, S.L.; Mattison, D.R.; Ye, A.; Pollack, A.Z.; Bloom, M.S.; Mendola, P.; Lynch, K.L.; Wactawski-Wende, J.; Schisterman, E.F.

    2013-01-01

    STUDY QUESTION Do ovulatory hormone profiles among healthy premenopausal women differ between women with and without sporadic anovulation? SUMMARY ANSWER Women with one anovulatory cycle tended to have lower estradiol, progesterone and LH peak levels during their ovulatory cycle. WHAT IS KNOWN ALREADY Anovulation occurs sporadically in healthy premenopausal women, but the influence of hormones in a preceding cycle and the impact on a subsequent cycle's hormone levels is unknown. STUDY DESIGN, SIZE, DURATION The BioCycle Study was a prospective cohort including 250 healthy regularly menstruating women, 18–44 years of age, from Western New York with no history of menstrual or ovulation disorders. The women were followed with up to eight study visits per cycle for two cycles, most of which were consecutive. PARTICIPANTS/MATERIALS, SETTING AND METHODS All study visits were timed to menstrual cycle phase using fertility monitors and located at the University at Buffalo women's health research center from 2005 to 2007. The main outcomes measured were estradiol, progesterone, LH and follicle-stimulating hormone levels in serum at up to 16 visits over two cycles. Anovulation was defined as peak serum progesterone concentrations ≤5 ng/ml and no serum LH peak detected during the mid- or late-luteal phase visit. MAIN RESULTS AND THE ROLE OF CHANCE Reproductive hormone concentrations were lower during anovulatory cycles, but significant reductions were also observed in estradiol (−25%, P = 0.003) and progesterone (−22%, P = 0.001) during the ovulatory cycles of women with one anovulatory cycle compared with women with two ovulatory cycles. LH peak concentrations were decreased in the ovulatory cycle of women with an anovulatory cycle (significant amplitude effect, P = 0.004; geometric mean levels 38% lower, P cycles, and no ultrasound assessment of ovulation was available. Data were missing for a total of 168 of a possible 4072 cycle visits (4.1%), though all women had

  5. A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis

    Science.gov (United States)

    Fogh, Isabella; Ratti, Antonia; Gellera, Cinzia; Lin, Kuang; Tiloca, Cinzia; Moskvina, Valentina; Corrado, Lucia; Sorarù, Gianni; Cereda, Cristina; Corti, Stefania; Gentilini, Davide; Calini, Daniela; Castellotti, Barbara; Mazzini, Letizia; Querin, Giorgia; Gagliardi, Stella; Del Bo, Roberto; Conforti, Francesca L.; Siciliano, Gabriele; Inghilleri, Maurizio; Saccà, Francesco; Bongioanni, Paolo; Penco, Silvana; Corbo, Massimo; Sorbi, Sandro; Filosto, Massimiliano; Ferlini, Alessandra; Di Blasio, Anna M.; Signorini, Stefano; Shatunov, Aleksey; Jones, Ashley; Shaw, Pamela J.; Morrison, Karen E.; Farmer, Anne E.; Van Damme, Philip; Robberecht, Wim; Chiò, Adriano; Traynor, Bryan J.; Sendtner, Michael; Melki, Judith; Meininger, Vincent; Hardiman, Orla; Andersen, Peter M.; Leigh, Nigel P.; Glass, Jonathan D.; Overste, Daniel; Diekstra, Frank P.; Veldink, Jan H.; van Es, Michael A.; Shaw, Christopher E.; Weale, Michael E.; Lewis, Cathryn M.; Williams, Julie; Brown, Robert H.; Landers, John E.; Ticozzi, Nicola; Ceroni, Mauro; Pegoraro, Elena; Comi, Giacomo P.; D'Alfonso, Sandra; van den Berg, Leonard H.; Taroni, Franco; Al-Chalabi, Ammar; Powell, John; Silani, Vincenzo; Brescia Morra, Vincenzo; Filla, Alessandro; Massimo, Filosto; Marsili, Angela; Viviana, Pensato; Puorro, Giorgia; La Bella, Vincenzo; Logroscino, Giancarlo; Monsurrò, Maria Rosaria; Quattrone, Aldo; Simone, Isabella Laura; Ahmeti, Kreshnik B.; Ajroud-Driss, Senda; Armstrong, Jennifer; Birve, Anne; Blauw, Hylke M.; Bruijn, Lucie; Chen, Wenjie; Comeau, Mary C.; Cronin, Simon; Soraya, Gkazi Athina; Grab, Josh D.; Groen, Ewout J.; Haines, Jonathan L.; Heller, Scott; Huang, Jie; Hung, Wu-Yen; Jaworski, James M.; Khan, Humaira; Langefeld, Carl D.; Marion, Miranda C.; McLaughlin, Russell L.; Miller, Jack W.; Mora, Gabriele; Pericak-Vance, Margaret A.; Rampersaud, Evadnie; Siddique, Nailah; Siddique, Teepu; Smith, Bradley N.; Sufit, Robert; Topp, Simon; Vance, Caroline; van Vught, Paul; Yang, Yi; Zheng, J.G.

    2014-01-01

    Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (∼90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10−8; OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10−9; OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10−9; OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ∼12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci. PMID:24256812

  6. West nile virus prevalence across landscapes is mediated by local effects of agriculture on vector and host communities.

    Science.gov (United States)

    Crowder, David W; Dykstra, Elizabeth A; Brauner, Jo Marie; Duffy, Anne; Reed, Caitlin; Martin, Emily; Peterson, Wade; Carrière, Yves; Dutilleul, Pierre; Owen, Jeb P

    2013-01-01

    Arthropod-borne viruses (arboviruses) threaten the health of humans, livestock, and wildlife. West Nile virus (WNV), the world's most widespread arbovirus, invaded the United States in 1999 and rapidly spread across the county. Although the ecology of vectors and hosts are key determinants of WNV prevalence across landscapes, the factors shaping local vector and host populations remain unclear. Here, we used spatially-explicit models to evaluate how three land-use types (orchards, vegetable/forage crops, natural) and two climatic variables (temperature, precipitation) influence the prevalence of WNV infections and vector/host distributions at landscape and local spatial scales. Across landscapes, we show that orchard habitats were associated with greater prevalence of WNV infections in reservoirs (birds) and incidental hosts (horses), while increased precipitation was associated with fewer infections. At local scales, orchard habitats increased the prevalence of WNV infections in vectors (mosquitoes) and the abundance of mosquitoes and two key reservoir species, the American robin and the house sparrow. Thus, orchard habitats benefitted WNV vectors and reservoir hosts locally, creating focal points for the transmission of WNV at landscape scales in the presence of suitable climatic conditions.

  7. Diagnostic sensitivity and specificity of in situ hybridization and immunohistochemistry for Eastern equine encephalitis virus and West Nile virus in formalin-fixed, paraffin-embedded brain tissue of horses.

    Science.gov (United States)

    Pennick, Kate E; McKnight, Christy A; Patterson, Jon S; Latimer, Kenneth S; Maes, Roger K; Wise, Annabel G; Kiupel, Matti

    2012-03-01

    Immunohistochemistry (IHC) and in situ hybridization (ISH) can be used either to detect or to differentiate between Eastern equine encephalitis virus (EEEV) and West Nile virus (WNV) within formalin-fixed, paraffin-embedded (FFPE) brain tissue of horses. To compare the diagnostic sensitivity and specificity of ISH and IHC, FFPE brain tissue from 20 EEEV-positive horses and 16 WNV-positive horses were tested with both EEEV and WNV oligoprobes and EEEV- and WNV-specific antibodies. Reverse transcription polymerase chain reaction (RT-PCR) for detection of EEEV and WNV was used as the gold standard to confirm infection. All horses that tested positive for EEEV by RT-PCR also tested positive by IHC and ISH, except for 1 case that was false-negative by ISH. In contrast, all horses that tested positive for WNV by RT-PCR tested negative by IHC and only 2 horses tested positive by ISH. No false-positives were detected with either method for both viruses. Both IHC and ISH are highly specific and sensitive diagnostic methods to detect EEEV in equine FFPE brain tissues, although neither appear effective for the diagnosis of WNV in equine neurologic cases.

  8. Adverse Effects of Sporadic Dialysis on Body Composition.

    Science.gov (United States)

    Workeneh, Biruh; Shypailo, Roman; DeCastro, Iris; Shah, Maulin; Guffey, Danielle; Minard, Charles G; Mitch, William E

    2015-01-01

    The aim of this study is to analyze the body composition of patients receiving emergent dialysis and compare their body cell mass (BCM) and fat-free mass (FFM) with those of normal subjects. The care of patients receiving sporadic, emergent dialysis treatment is a growing public health concern and the magnitude of muscle wasting that occurs in this population is not known. We used a cross-sectional design with matching to determine differences in total body potassium--an indicator of both BCM and FFM--between emergent dialysis patients and healthy normal subjects. We studied 22 subjects using a 40K counter that measures BCM and FFM and compared them to controls after matching with sex, height and weight. In the matched comparison, BCM and FFM were significantly lower in subjects with end-stage renal disease (ESRD). Unadjusted BCM was 4.7 kg lower and FFM was 8.8 kg lower for those with ESRD compared to those without ESRD (p FFM (7.7 kg) in the ESRD subjects (p = 0.004). After adjusting for age, height, weight and gender, BCM and FFM were lower by 4.2 and 7.8 kg, respectively (p FFM loss over time was significant, with the ESRD subjects demonstrating 2.2 kg per year decline (p = 0.01). We conclude that among other consequences, muscle wasting indicated by decline in BCM and FFM is a significant concern in the growing emergent dialysis population. © 2015 S. Karger AG, Basel.

  9. West Nile Review: 15 Years of Human Disease in South Dakota, 2002-2016.

    Science.gov (United States)

    Kightlinger, Lon

    2017-08-01

    During the past 15 years, 2002-2016, West Nile virus (WNV) has emerged in South Dakota resulting in 509 neuroinvasive disease (NID) cases, 745 hospitalizations and 38 deaths. Culex tarsalis is the state's primary mosquito vector. South Dakota's average annual incidence of WNV-NID and death rate are the highest of any state in the U.S. WNV cases have been reported from all counties in the state. All age groups have been infected with cases peaking in the 40-44 year age group, but deaths peaking in cases 70 years and older. Although South Dakota's WNV season lasts six months, May-October, the first week of August has been the peak week of WNV disease onsets. West Nile is now enzootic in South Dakota. Every citizen, local mosquito control programs, medical and public health infrastructures must continue to prevent and respond to annual WNV outbreaks, and prepare for the next arboviral disease to emerge. Copyright© South Dakota State Medical Association.

  10. Prevalence of West Nile virus in migratory birds during spring and fall migration

    Science.gov (United States)

    Dusek, Robert J.; McLean, R.G.; Kramer, L.D.; Ubico, S.R.; Dupuis, A.P.; Ebel, G.D.; Guptill, S.C.

    2009-01-01

    To investigate the role of migratory birds in the dissemination of West Nile virus (WNV), we measured the prevalence of infectious WNV and specific WNV neutralizing antibodies in birds, principally Passeriformes, during spring and fall migrations in the Atlantic and Mississippi flyways from 2001-2003. Blood samples were obtained from 13,403 birds, representing 133 species. Specific WNV neutralizing antibody was detected in 254 resident and migratory birds, representing 39 species, and was most commonly detected in northern cardinals (Cardinalis cardinalis) (9.8%, N = 762) and gray catbirds (Dumetella carolinensis) (3.2%,N = 3188). West Nile virus viremias were detected in 19 birds, including 8 gray catbirds, and only during the fall migratory period. These results provide additional evidence that migratory birds may have been a principal agent for the spread of WNV in North America and provide data on the occurrence of WNV in a variety of bird species. Copyright ?? 2009 by The American Society of Tropical Medicine and Hygiene.

  11. Susceptibility of Carrion Crows to Experimental Infection with Lineage 1 and 2 West Nile Viruses.

    Science.gov (United States)

    Lim, Stephanie M; Brault, Aaron C; van Amerongen, Geert; Bosco-Lauth, Angela M; Romo, Hannah; Sewbalaksing, Varsha D; Bowen, Richard A; Osterhaus, Albert D M E; Koraka, Penelope; Martina, Byron E E

    2015-08-01

    West Nile virus (WNV) outbreaks in North America have been characterized by substantial die-offs of American crows (Corvus brachyrhynchos). In contrast, a low incidence of bird deaths has been observed during WNV epidemic activity in Europe. To examine the susceptibility of the western European counterpart of American crows, we inoculated carrion crows (Corvus corone) with WNV strains isolated in Greece (Gr-10), Italy (FIN and Ita09), and Hungary (578/10) and with the highly virulent North American genotype strain (NY99). We also inoculated American crows with a selection of these strains to examine the strains' virulence in a highly susceptible bird species. Infection with all strains, except WNV FIN, resulted in high rates of death and high-level viremia in both bird species and virus dissemination to several organs. These results suggest that carrion crows are highly susceptible to WNV and may potentially be useful as part of dead bird surveillance for early warning of WNV activity in Europe.

  12. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

    Science.gov (United States)

    Bishop, Matthew T.; Will, Robert G.; Manson, Jean C.

    2010-01-01

    The biological determinants of the phenotypic variation in sporadic Creutzfeldt-Jakob disease (sCJD) are unknown. To categorize sCJD cases, the prion protein (PrP) codon 129 genotype and the biochemical characteristics of the disease-associated form of PrP (PrPSc) can be combined to form six subgroups (MM1, MM2, MV1, MV2, VV1, and VV2). This classification largely correlates with the known variation in the clinical and pathological features of sCJD, with the MM1 and MV1 cases representing the “classic” phenotype of sCJD. To address how this classification relates to different strains of sCJD we have inoculated each subgroup of sCJD to a panel of mice expressing different forms of the human PRNP gene (129MM, 129VV, and 129MV). We have established that all subtypes are transmissible to at least one genotype of mouse, and both agent and host factors determine transmission efficiency and the form of PrPSc deposited in the brain. Moreover, we have identified four distinct strains of sCJD using our in vivo strain typing panel. PMID:20547859

  13. Facing and managing natural disasters in the Sporades islands, Greece

    Science.gov (United States)

    Karanikola, P.; Panagopoulos, T.; Tampakis, S.; Karantoni, M. I.; Tsantopoulos, G.

    2014-04-01

    The region of the Sporades islands located in central Greece is at the mercy of many natural phenomena, such as earthquakes due to the marine volcano Psathoura and the rift of Anatolia, forest fires, floods, landslides, storms, hail, snowfall and frost. The present work aims at studying the perceptions and attitudes of the residents regarding how they face and manage natural disasters. A positive public response during a hazard crisis depends not only upon the availability and good management of a civil defense plan but also on the knowledge and perception of the possible hazards by the local population. It is important for the stakeholders to know what the citizens expect so that the necessary structures can be developed in the phase of preparation and organization. The residents were asked their opinion about what they think should be done by the stakeholders after a catastrophic natural disaster, particularly about the immediate response of stakeholders and their involvement and responsibilities at different, subsequent intervals of time following the disaster. The residents were also asked about the most common disasters that happen in their region and about the preparation activities of the stakeholders.

  14. The roles of mosquito and bird communities on the prevalence of West Nile virus in urban wetland and residential habitats

    Science.gov (United States)

    Johnson, Brian J.; Munafo, Kristin; Shappell, Laura; Tsipoura, Nellie; Robson, Mark; Ehrenfeld, Joan; Sukhdeo, Michael V. K.

    2014-01-01

    This study investigated the impacts of urban wetlands and their adjacent residential environments on the transmission dynamics of West Nile virus (WNV) within the state of New Jersey (USA). A working hypothesis was that urban wetlands decrease the local prevalence of WNV through the dilution effect from increased bird diversity, and through relative reductions in the numbers of competent avian host and mosquito species commonly associated with WNV. Surveys of mosquito and bird communities were undertaken at six urban wetlands and their adjacent residential environments over two seasons (2009, 2010). The community compositions of both avian and mosquito species differed significantly across habitats, and over relatively short geographical distances. Residential areas contained significantly higher proportions of WNV-competent mosquito species (31.25±5.3 %; e.g. Culex pipiens and Culex restuans), and WNV-competent avian host species (62.8±2.3 %, e.g. House Sparrow and American Robin) when compared to adjacent urban wetlands (13.5±2.1 %; 35.4±2.1 % respectively). Correspondingly, WNV infection rates within local Culex spp. populations indicate that WNV was more prevalent within residential areas (28.53/1000) compared to wetlands (16.77/1000). Large urban wetlands (>100 ha) produced significantly lower weekly WNV infection rates in local Culex spp. (6.67±2.84/1000) compared to small (urban wetlands contained significantly more species than small wetland patches. These results confirm that the community compositions of mosquito and avian hosts are important drivers in WNV infections, and that the ecological conditions that favor transmission are more strongly associated with urban residential environments than with adjacent urban wetlands. PMID:25484570

  15. Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism

    Science.gov (United States)

    Roberts, Stephanie A.; Moon, Jennifer E.; Dauber, Andrew; Smith, Jessica R.

    2018-01-01

    Background Primary nonautoimmune hyperthyroidism is a rare cause of neonatal hyperthyroidism. This results from an activating mutation in the thyrotropin-receptor (TSHR). It can be inherited in an autosomal dominant manner or occur sporadically as a de novo mutation. Affected individuals display a wide phenotype from severe neonatal to mild subclinical hyperthyroidism. We describe a 6-month-old boy with a de novo mutation in the TSHR gene who presented with accelerated growth, enlarging head circumference, tremor and thyrotoxicosis. Methods Genomic DNA from the patient’s and parents’ peripheral blood leukocytes was extracted. Exons 9 and 10 of the TSHR gene were amplified by PCR and sequenced. Results Sequencing exon 10 of the TSHR gene revealed a novel heterozygous missense mutation substituting cytosine to adenine at nucleotide position 1534 in the patient’s peripheral blood leukocytes. This leads to a substitution of leucine to methionine at amino acid position 512. The mutation was absent in the parents. In silico modeling by PolyPhen-2 and SIFT predicted the mutation to be deleterious. Conclusions The p.Leu512Met mutation (c.l534C>A) of the TSHR gene has not been previously described in germline or somatic mutations. This case presentation highlights the possibility of mild thyrotoxicosis in affected individuals and contributes to the understanding of sporadic non-autoimmune primary hyperthyroidism. PMID:28195550

  16. Heterozygous genotype at codon 129 correlates with prolonged disease course in Heidenhain variant sporadic CJD: case report.

    Science.gov (United States)

    Townley, Ryan A; Dawson, Elliot T; Drubach, Daniel A

    2018-02-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapid and fatal neurodegenerative disease defined by misfolded prion proteins accumulating in the brain. A minority of cases initially present with posterior cortical atrophy (PCA) phenotype, also known as Heidenhain variant or visual variant CJD. This case provides further evidence of sCJD presenting as PCA. The case also provides evidence for early DWI changes and cortical atrophy over 30 months before neurologic decline and subsequent death. The prolonged disease course correlates with prion protein codon 129 heterozygosity and coexistence of multiple prion strains.

  17. Identification of CD8(+) T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby; Lelic, A.; Parsons, R.

    2010-01-01

    bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell...

  18. West Nile virus isolated from a Virginia opossum (Didelphis virginiana) in northwestern Missouri, USA, 2012.

    Science.gov (United States)

    Bosco-Lauth, Angela; Harmon, Jessica R; Lash, R Ryan; Weiss, Sonja; Langevin, Stanley; Savage, Harry M; Godsey, Marvin S; Burkhalter, Kristen; Root, J Jeffrey; Gidlewski, Thomas; Nicholson, William L; Brault, Aaron C; Komar, Nicholas

    2014-10-01

    We describe the isolation of West Nile virus (WNV; Flaviviridae, Flavivirus) from blood of a Virginia opossum (Didelphis virginiana) collected in northwestern Missouri, USA in August 2012. Sequencing determined that the virus was related to lineage 1a WNV02 strains. We discuss the role of wildlife in WNV disease epidemiology.

  19. A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection

    International Nuclear Information System (INIS)

    Pierson, Theodore C.; Sanchez, Melissa D.; Puffer, Bridget A.; Ahmed, Asim A.; Geiss, Brian J.; Valentine, Laura E.; Altamura, Louis A.; Diamond, Michael S.; Doms, Robert W.

    2006-01-01

    West Nile virus (WNV) is a neurotropic flavivirus within the Japanese encephalitis antigenic complex that is responsible for causing West Nile encephalitis in humans. The surface of WNV virions is covered by a highly ordered icosahedral array of envelope proteins that is responsible for mediating attachment and fusion with target cells. These envelope proteins are also primary targets for the generation of neutralizing antibodies in vivo. In this study, we describe a novel approach for measuring antibody-mediated neutralization of WNV infection using virus-like particles that measure infection as a function of reporter gene expression. These reporter virus particles (RVPs) are produced by complementation of a sub-genomic replicon with WNV structural proteins provided in trans using conventional DNA expression vectors. The precision and accuracy of this approach stem from an ability to measure the outcome of the interaction between antibody and viral antigens under conditions that satisfy the assumptions of the law of mass action as applied to virus neutralization. In addition to its quantitative strengths, this approach allows the production of WNV RVPs bearing the prM-E proteins of different WNV strains and mutants, offering considerable flexibility for the study of the humoral immune response to WNV in vitro. WNV RVPs are capable of only a single round of infection, can be used under BSL-2 conditions, and offer a rapid and quantitative approach for detecting virus entry and its inhibition by neutralizing antibody

  20. Seroprevalence screening for the West Nile virus in Malaysia's Orang Asli population.

    Science.gov (United States)

    Marlina, Suria; Radzi, Siti Fatimah Muhd; Lani, Rafidah; Sieng, Khor Chee; Rahim, Nurul Farhana Abdul; Hassan, Habibi; Li-Yen, Chang; AbuBakar, Sazaly; Zandi, Keivan

    2014-12-17

    West Nile virus (WNV) infection is an emerging zoonotic disease caused by an RNA virus of the genus Flavivirus. WNV is preserved in the environment through cyclic transmission, with mosquitoes, particularly Culex species, serving as a vector, birds as an amplifying host and humans and other mammals as dead-end hosts. To date, no studies have been carried out to determine the prevalence of the WNV antibody in Malaysia. The aim of this study was to screen for the seroprevalence of the WNV in Malaysia's Orang Asli population. Serum samples of 742 Orang Asli were collected in seven states in peninsular Malaysia. The samples were assessed to determine the seroprevalence of WNV immunoglobulin (Ig)G with the WNV IgG enzyme-linked immunosorbent assay (ELISA) method. For each individual, we documented the demographic factors. Anti-dengue and anti-tick-borne encephalitis virus IgG ELISA were also performed to rule out a cross reaction. All statistical analyses were performed using the GraphPad Prism 6 (GraphPad Software, Inc.); p values of less than 0.05 were considered significant. The serosurvey included 298 men (40.16%) and 444 women (59.84%) of Malaysia's Orang Asli. Anti-WNV IgG was found in 9 of the 742 samples (1.21%). The seroprevalence was 0.67% (2 of 298) in men and 1.58% (7 of 444) in women. The presence of anti-WNV IgG was found not to be associated with gender but, however, did correlate with age. The peak seroprevalence was found to be 2.06% (2 of 97) in individuals between 30 to 42 years of age. No previous studies have examined the seroprevalence of the WNV antibody in the human population in Malaysia, and no clinical reports of infections have been made. Screening for the WNV seroprevalence is very significant because of many risk factors contribute to the presence of WNV in Malaysia, such as the abundance of Culex mosquitoes as the main vector and a high degree of biodiversity, including migratory birds that serve as a reservoir to the virus.

  1. Modeling Late-Onset Sporadic Alzheimer’s Disease through BMI1 Deficiency

    Directory of Open Access Journals (Sweden)

    Anthony Flamier

    2018-05-01

    Full Text Available Late-onset sporadic Alzheimer’s disease (AD is the most prevalent form of dementia, but its origin remains poorly understood. The Bmi1/Ring1 protein complex maintains transcriptional repression of developmental genes through histone H2A mono-ubiquitination, and Bmi1 deficiency in mice results in growth retardation, progeria, and neurodegeneration. Here, we demonstrate that BMI1 is silenced in AD brains, but not in those with early-onset familial AD, frontotemporal dementia, or Lewy body dementia. BMI1 expression was also reduced in cortical neurons from AD patient-derived induced pluripotent stem cells but not in neurons overexpressing mutant APP and PSEN1. BMI1 knockout in human post-mitotic neurons resulted in amyloid beta peptide secretion and deposition, p-Tau accumulation, and neurodegeneration. Mechanistically, BMI1 was required to repress microtubule associated protein tau (MAPT transcription and prevent GSK3beta and p53 stabilization, which otherwise resulted in neurodegeneration. Restoration of BMI1 activity through genetic or pharmaceutical approaches could represent a therapeutic strategy against AD.

  2. West Nile Virus Drug Discovery

    Directory of Open Access Journals (Sweden)

    Siew Pheng Lim

    2013-12-01

    Full Text Available The outbreak of West Nile virus (WNV in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.

  3. Antibody responses in humans infected with newly emerging strains of West Nile Virus in Europe.

    Directory of Open Access Journals (Sweden)

    Stefan Chabierski

    Full Text Available Infection with West Nile Virus (WNV affects an increasing number of countries worldwide. Although most human infections result in no or mild flu-like symptoms, the elderly and those with a weakened immune system are at higher risk for developing severe neurological disease. Since its introduction into North America in 1999, WNV has spread across the continental United States and caused annual outbreaks with a total of 36,000 documented clinical cases and ∼1,500 deaths. In recent years, outbreaks of neuroinvasive disease also have been reported in Europe. The WNV strains isolated during these outbreaks differ from those in North America, as sequencing has revealed that distinct phylogenetic lineages of WNV concurrently circulate in Europe, which has potential implications for the development of vaccines, therapeutics, and diagnostic tests. Here, we studied the human antibody response to European WNV strains responsible for outbreaks in Italy and Greece in 2010, caused by lineage 1 and 2 strains, respectively. The WNV structural proteins were expressed as a series of overlapping fragments fused to a carrier-protein, and binding of IgG in sera from infected persons was analyzed. The results demonstrate that, although the humoral immune response to WNV in humans is heterogeneous, several dominant peptides are recognized.

  4. West Nile Virus in the United States — A Historical Perspective

    Directory of Open Access Journals (Sweden)

    John T. Roehrig

    2013-12-01

    Full Text Available Prior to 1999, West Nile virus (WNV was a bit player in the screenplay of global vector-borne viral diseases. First discovered in the West Nile District of Uganda in 1937, this Culex sp.-transmitted virus was known for causing small human febrile outbreaks in Africa and the Middle East. Prior to 1995, the last major human WNV outbreak was in the 1950s in Israel. The epidemiology and ecology of WNV began to change in the mid-1990s when an epidemic of human encephalitis occurred in Romania. The introduction of WNV into Eastern Europe was readily explained by bird migration between Africa and Europe. The movement of WNV from Africa to Europe could not, however, predict its surprising jump across the Atlantic Ocean to New York City and the surrounding areas of the United States (U.S.. This movement of WNV from the Eastern to Western Hemisphere in 1999, and its subsequent dissemination throughout two continents in less than ten years is widely recognized as one of the most significant events in arbovirology during the last two centuries. This paper documents the early events of the introduction into and the spread of WNV in the Western Hemisphere.

  5. West Nile Virus Outbreak in Houston and Harris County, Texas, USA, 2014.

    Science.gov (United States)

    Martinez, Diana; Murray, Kristy O; Reyna, Martin; Arafat, Raouf R; Gorena, Roberto; Shah, Umair A; Debboun, Mustapha

    2017-08-01

    Since 2002, West Nile virus (WNV) has been detected every year in Houston and the surrounding Harris County, Texas. In 2014, the largest WNV outbreak to date occurred, comprising 139 cases and causing 2 deaths. Additionally, 1,286 WNV-positive mosquito pools were confirmed, the most reported in a single mosquito season.

  6. The subcatchment- and catchment-scale hydrology of a boreal headwater peatland complex with sporadic permafrost.

    Science.gov (United States)

    Sonnentag, O.; Helbig, M.; Connon, R.; Hould Gosselin, G.; Ryu, Y.; Karoline, W.; Hanisch, J.; Moore, T. R.; Quinton, W. L.

    2017-12-01

    The permafrost region of the Northern Hemisphere has been experiencing twice the rate of climate warming compared to the rest of the Earth, resulting in the degradation of the cryosphere. A large portion of the high-latitude boreal forests of northwestern Canada grows on low-lying organic-rich lands with relative warm and thin isolated, sporadic and discontinuous permafrost. Along this southern limit of permafrost, increasingly warmer temperatures have caused widespread permafrost thaw leading to land cover changes at unprecedented rates. A prominent change includes wetland expansion at the expense of Picea mariana (black spruce)-dominated forest due to ground surface subsidence caused by the thawing of ice-rich permafrost leading to collapsing peat plateaus. Recent conceptual advances have provided important new insights into high-latitude boreal forest hydrology. However, refined quantitative understanding of the mechanisms behind water storage and movement at subcatchment and catchment scales is needed from a water resources management perspective. Here we combine multi-year daily runoff measurements with spatially explicit estimates of evapotranspiration, modelled with the Breathing Earth System Simulator, to characterize the monthly growing season catchment scale ( 150 km2) hydrological response of a boreal headwater peatland complex with sporadic permafrost in the southern Northwest Territories. The corresponding water budget components at subcatchment scale ( 0.1 km2) were obtained from concurrent cutthroat flume runoff and eddy covariance evapotranspiration measurements. The highly significant linear relationships for runoff (r2=0.64) and evapotranspiration (r2=0.75) between subcatchment and catchment scales suggest that the mineral upland-dominated downstream portion of the catchment acts hydrologically similar to the headwater portion dominated by boreal peatland complexes. Breakpoint analysis in combination with moving window statistics on multi

  7. A comparison between Lynch syndrome and sporadic colorectal cancer survivors' satisfaction with their healthcare providers.

    Science.gov (United States)

    Burton-Chase, Allison M; Parker, Wendy M; Polivka, Katrina M; Gritz, Ellen R; Amos, Christopher I; Lu, Karen H; Lynch, Patrick M; Rodriguez-Bigas, Miguel A; Nancy You, Y; Peterson, Susan K

    2017-03-01

    This study evaluated provider satisfaction in a sample of colorectal cancer (CRC) survivors with and without Lynch syndrome (LS). Participants were case-case-matched CRC survivors with (n = 75) or without (n = 75) LS (mean age of 55; range: 27-93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P < 0.05), interpersonal treatment (78.58 vs. 85.30; P < 0.05), and knowledge of the patient (60.34 vs. 69.86; P < 0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center (CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  8. Epidemiology and spatio-temporal analysis of West Nile virus in horses in Spain between 2010 and 2016.

    Science.gov (United States)

    García-Bocanegra, I; Belkhiria, J; Napp, S; Cano-Terriza, D; Jiménez-Ruiz, S; Martínez-López, B

    2018-04-01

    During the last decade, West Nile virus (WNV) outbreaks have increased sharply in both horses and human in Europe. The aims of this study were to evaluate characteristics and spatio-temporal distribution of WNV outbreaks in horses in Spain between 2010 and 2016 in order to identify the environmental variables most associated with WNV occurrence and to generate high-resolution WNV suitability maps to inform risk-based surveillance strategies in this country. Between August 2010 and November 2016, a total of 403 WNV suspected cases were investigated, of which, 177 (43.9%) were laboratory confirmed. Mean values of morbidity, mortality and case fatality rates were 7.5%, 1.6% and 21.2%, respectively. The most common clinical symptoms were as follows: tiredness/apathy, recumbency, muscular tremor, ataxia, incoordination and hyperaesthesia. The outbreaks confirmed during the last 7 years, with detection of WNV RNA lineage 1 in 2010, 2012, 2013, 2015 and 2016, suggest an endemic circulation of the virus in Spain. The spatio-temporal distribution of WNV outbreaks in Spain was not homogeneous, as most of them (92.7%) were concentrated in western part of Andalusia (southern Spain) and significant clusters were detected in this region in two non-consecutive years. These findings were supported by the results of the space-time scan statistics permutation model. A presence-only MaxEnt ecological niche model was used to generate a suitability map for WNV occurrence in Andalusia. The most important predictors selected by the Ecological Niche Modeling were as follows: mean annual temperature (49.5% contribution), presence of Culex pipiens (19.5% contribution), mean annual precipitation (16.1% contribution) and distance to Ramsar wetlands (14.9% contribution). Our results constitute an important step for understanding WNV emergence and spread in Spain and will provide valuable information for the development of more cost-effective surveillance and control programmes and improve the

  9. CAMS newly detected meteor showers and the sporadic background

    Science.gov (United States)

    Jenniskens, P.; Nénon, Q.; Gural, P. S.; Albers, J.; Haberman, B.; Johnson, B.; Morales, R.; Grigsby, B. J.; Samuels, D.; Johannink, C.

    2016-03-01

    The Cameras for Allsky Meteor Surveillance (CAMS) video-based meteoroid orbit survey adds 60 newly identified showers to the IAU Working List of Meteor Showers (numbers 427, 445-446, 506-507, and part of 643-750). 28 of these are also detected in the independent SonotaCo survey. In total, 230 meteor showers and shower components are identified in CAMS data, 177 of which are detected in at least two independent surveys. From the power-law size frequency distribution of detected showers, we extrapolate that 36% of all CAMS-observed meteors originated from ∼700 showers above the N = 1 per 110,000 shower limit. 71% of mass falling to Earth from streams arrives on Jupiter-family type orbits. The transient Geminids account for another 15%. All meteoroids not assigned to streams form a sporadic background with highest detected numbers from the apex source, but with 98% of mass falling in from the antihelion source. Even at large ∼7-mm sizes, a Poynting-Robertson drag evolved population is detected, which implies that the Grün et al. collisional lifetimes at these sizes are underestimated by about a factor of 10. While these large grains survive collisions, many fade on a 104-y timescale, possibly because they disintegrate into smaller particles by processes other than collisions, leaving a more resilient population to evolve.

  10. Sporadic Creutzfeldt–Jakob disease with cerebellar ataxia at onset in the UK

    Science.gov (United States)

    Cooper, S A; Murray, K L; Heath, C A; Will, R G; Knight, R S G

    2006-01-01

    Objective To determine the frequency, in the UK, of sporadic Creutzfeldt–Jakob Disease (sCJD) with a cerebellar ataxic onset, and to describe the clinical features of the syndrome. Methods A retrospective review of autopsy‐proved cases of sCJD cases in the UK, 1990–2005, identifying those presenting with cerebellar features without early cognitive decline. Results 29 of 618 (5%) patients with sCJD had an isolated cerebellar onset. Mean illness duration was 9 months. Subsequently, 21 (72%) developed myoclonus and 23 (79%) developed pyramidal features. Magnetic resonance imaging showed high signal in the basal ganglia in 11 of 14 (79%) patients. 7 of 15 (47%) patients were valine homozygotic at prion protein gene (PRNP)‐129. Only 8 (28%) cases were referred to the surveillance unit after death. Conclusion A better definition of sCJD presenting with an isolated cerebellar syndrome might improve future case recognition and contribute to the determination of its cause. PMID:16835290

  11. Wernicke-Korsakoff syndrome as a rare phenotype of sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Bielewicz, Joanna; Szczepańska-Szerej, Anna; Ogórek, Magdalena; Dropko, Piotr; Wojtal, Katarzyna; Rejdak, Konrad

    2018-03-04

    We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14-3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis.

  12. Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report

    Directory of Open Access Journals (Sweden)

    Cracco Laura

    2011-10-01

    Full Text Available Abstract Background Sporadic fatal insomnia (sFI and fatal familial insomnia (FFI are rare human prion diseases. Case Presentation We report a case of a 33-year-old female who died of a prion disease for whom the diagnosis of sFI or FFI was not considered clinically. Following death of this patient, an interview with a close family member indicated the patient's illness included a major change in her sleep pattern, corroborating the reported autopsy diagnosis of sFI. Genetic tests identified no prion protein (PrP gene mutation, but neuropathological examination and molecular study showed protease-resistant PrP (PrPres in several brain regions and severe atrophy of the anterior-ventral and medial-dorsal thalamic nuclei similar to that described in FFI. Conclusions In patients with suspected prion disease, a characteristic change in sleep pattern can be an important clinical clue for identifying sFI or FFI; polysomnography (PSG, genetic analysis, and nuclear imaging may aid in diagnosis.

  13. Clinical Perspective of Oxidative Stress in Sporadic ALS

    Science.gov (United States)

    D’Amico, Emanuele; Factor-Litvak, Pam; Santella, Regina M.; Mitsumoto, Hiroshi

    2013-01-01

    Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis. PMID:23797033

  14. SURF IA Conflict Detection and Resolution Algorithm Evaluation

    Science.gov (United States)

    Jones, Denise R.; Chartrand, Ryan C.; Wilson, Sara R.; Commo, Sean A.; Barker, Glover D.

    2012-01-01

    The Enhanced Traffic Situational Awareness on the Airport Surface with Indications and Alerts (SURF IA) algorithm was evaluated in a fast-time batch simulation study at the National Aeronautics and Space Administration (NASA) Langley Research Center. SURF IA is designed to increase flight crew situation awareness of the runway environment and facilitate an appropriate and timely response to potential conflict situations. The purpose of the study was to evaluate the performance of the SURF IA algorithm under various runway scenarios, multiple levels of conflict detection and resolution (CD&R) system equipage, and various levels of horizontal position accuracy. This paper gives an overview of the SURF IA concept, simulation study, and results. Runway incursions are a serious aviation safety hazard. As such, the FAA is committed to reducing the severity, number, and rate of runway incursions by implementing a combination of guidance, education, outreach, training, technology, infrastructure, and risk identification and mitigation initiatives [1]. Progress has been made in reducing the number of serious incursions - from a high of 67 in Fiscal Year (FY) 2000 to 6 in FY2010. However, the rate of all incursions has risen steadily over recent years - from a rate of 12.3 incursions per million operations in FY2005 to a rate of 18.9 incursions per million operations in FY2010 [1, 2]. The National Transportation Safety Board (NTSB) also considers runway incursions to be a serious aviation safety hazard, listing runway incursion prevention as one of their most wanted transportation safety improvements [3]. The NTSB recommends that immediate warning of probable collisions/incursions be given directly to flight crews in the cockpit [4].

  15. A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes.

    Directory of Open Access Journals (Sweden)

    Mehul S Suthar

    2013-02-01

    Full Text Available The actions of the RIG-I like receptor (RLR and type I interferon (IFN signaling pathways are essential for a protective innate immune response against the emerging flavivirus West Nile virus (WNV. In mice lacking RLR or IFN signaling pathways, WNV exhibits enhanced tissue tropism, indicating that specific host factors of innate immune defense restrict WNV infection and dissemination in peripheral tissues. However, the immune mechanisms by which the RLR and IFN pathways coordinate and function to impart restriction of WNV infection are not well defined. Using a systems biology approach, we defined the host innate immune response signature and actions that restrict WNV tissue tropism. Transcriptional profiling and pathway modeling to compare WNV-infected permissive (spleen and nonpermissive (liver tissues showed high enrichment for inflammatory responses, including pattern recognition receptors and IFN signaling pathways, that define restriction of WNV replication in the liver. Assessment of infected livers from Mavs(-/- × Ifnar(-/- mice revealed the loss of expression of several key components within the natural killer (NK cell signaling pathway, including genes associated with NK cell activation, inflammatory cytokine production, and NK cell receptor signaling. In vivo analysis of hepatic immune cell infiltrates from WT mice demonstrated that WNV infection leads to an increase in NK cell numbers with enhanced proliferation, maturation, and effector action. In contrast, livers from Mavs(-/- × Ifnar(-/- infected mice displayed reduced immune cell infiltration, including a significant reduction in NK cell numbers. Analysis of cocultures of dendritic and NK cells revealed both cell-intrinsic and -extrinsic roles for the RLR and IFN signaling pathways to regulate NK cell effector activity. Taken together, these observations reveal a complex innate immune signaling network, regulated by the RLR and IFN signaling pathways, that drives tissue

  16. Feeding patterns of potential West Nile virus vectors in south-west Spain.

    Directory of Open Access Journals (Sweden)

    Joaquín Muñoz

    Full Text Available Mosquito feeding behaviour determines the degree of vector-host contact and may have a serious impact on the risk of West Nile virus (WNV epidemics. Feeding behaviour also interacts with other biotic and abiotic factors that affect virus amplification and transmission.We identified the origin of blood meals in five mosquito species from three different wetlands in SW Spain. All mosquito species analysed fed with different frequencies on birds, mammals and reptiles. Both 'mosquito species' and 'locality' explained a similar amount of variance in the occurrence of avian blood meals. However, 'season of year' was the main factor explaining the presence of human blood meals. The differences in diet resulted in a marked spatial heterogeneity in the estimated WNV transmission risk. Culex perexiguus, Cx. modestus and Cx. pipiens were the main mosquito species involved in WNV enzootic circulation since they feed mainly on birds, were abundant in a number of localities and had high vector competence. Cx. perexiguus may also be important for WNV transmission to horses, as are Cx. pipiens and Cx. theileri in transmission to humans. Estimates of the WNV transmission risk based on mosquito diet, abundance and vector competence matched the results of previous WNV monitoring programs in the area. Our sensitivity analyses suggested that mosquito diet, followed by mosquito abundance and vector competence, are all relevant factors in understanding virus amplification and transmission risk in the studied wild ecosystems. At some of the studied localities, the risk of enzootic circulation of WNV was relatively high, even if the risk of transmission to humans and horses was less.Our results describe for first time the role of five WNV candidate vectors in SW Spain. Interspecific and local differences in mosquito diet composition has an important effect on the potential transmission risk of WNV to birds, horses and humans.

  17. Cost-Effectiveness of Alternative Blood-Screening Strategies for West Nile Virus in the United States.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: West Nile virus (WNV is endemic in the US, varying seasonally and by geographic region. WNV can be transmitted by blood transfusion, and mandatory screening of blood for WNV was recently introduced throughout the US. Guidelines for selecting cost-effective strategies for screening blood for WNV do not exist. METHODS AND FINDINGS: We conducted a cost-effectiveness analysis for screening blood for WNV using a computer-based mathematical model, and using data from prospective studies, retrospective studies, and published literature. For three geographic areas with varying WNV-transmission intensity and length of transmission season, the model was used to estimate lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios associated with alternative screening strategies in a target population of blood-transfusion recipients. We compared the status quo (baseline screening using a donor questionnaire to several strategies which differed by nucleic acid testing of either pooled or individual samples, universal versus targeted screening of donations designated for immunocompromised patients, and seasonal versus year-long screening. In low-transmission areas with short WNV seasons, screening by questionnaire alone was the most cost-effective strategy. In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients was the most cost-effective strategy. Seasonal screening of the entire recipient pool added minimal clinical benefit, with incremental cost-effectiveness ratios exceeding US$1.7 million per quality-adjusted life-year gained. Year-round screening offered no additional benefit compared to seasonal screening in any of the transmission settings. CONCLUSIONS: In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations

  18. Cost-effectiveness of alternative blood-screening strategies for West Nile Virus in the United States.

    Directory of Open Access Journals (Sweden)

    Caroline T Korves

    2006-02-01

    Full Text Available West Nile virus (WNV is endemic in the US, varying seasonally and by geographic region. WNV can be transmitted by blood transfusion, and mandatory screening of blood for WNV was recently introduced throughout the US. Guidelines for selecting cost-effective strategies for screening blood for WNV do not exist.We conducted a cost-effectiveness analysis for screening blood for WNV using a computer-based mathematical model, and using data from prospective studies, retrospective studies, and published literature. For three geographic areas with varying WNV-transmission intensity and length of transmission season, the model was used to estimate lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios associated with alternative screening strategies in a target population of blood-transfusion recipients. We compared the status quo (baseline screening using a donor questionnaire to several strategies which differed by nucleic acid testing of either pooled or individual samples, universal versus targeted screening of donations designated for immunocompromised patients, and seasonal versus year-long screening. In low-transmission areas with short WNV seasons, screening by questionnaire alone was the most cost-effective strategy. In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients was the most cost-effective strategy. Seasonal screening of the entire recipient pool added minimal clinical benefit, with incremental cost-effectiveness ratios exceeding USD 1.7 million per quality-adjusted life-year gained. Year-round screening offered no additional benefit compared to seasonal screening in any of the transmission settings.In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients is cost

  19. Improved reliability of serological tools for the diagnosis of West Nile fever in horses within Europe.

    Directory of Open Access Journals (Sweden)

    Cécile Beck

    2017-09-01

    Full Text Available West Nile Fever is a zoonotic disease caused by a mosquito-borne flavivirus, WNV. By its clinical sensitivity to the disease, the horse is a useful sentinel of infection. Because of the virus' low-level, short-term viraemia in horses, the primary tools used to diagnose WNV are serological tests. Inter-laboratory proficiency tests (ILPTs were held in 2010 and 2013 to evaluate WNV serological diagnostic tools suited for the European network of National Reference Laboratories (NRLs for equine diseases. These ILPTs were designed to evaluate the laboratories' and methods' performances in detecting WNV infection in horses through serology. The detection of WNV immunoglobulin G (IgG antibodies by ELISA is widely used in Europe, with 17 NRLs in 2010 and 20 NRLs in 2013 using IgG WNV assays. Thanks to the development of new commercial IgM capture kits, WNV IgM capture ELISAs were rapidly implemented in NRLs between 2010 (4 NRLs and 2013 (13 NRLs. The use of kits allowed the quick standardisation of WNV IgG and IgM detection assays in NRLs with more than 95% (20/21 and 100% (13/13 of satisfactory results respectively in 2013. Conversely, virus neutralisation tests (VNTs were implemented in 33% (7/21 of NRLs in 2013 and their low sensitivity was evidenced in 29% (2/7 of NRLs during this ILPT. A comparison of serological diagnostic methods highlighted the higher sensitivity of IgG ELISAs compared to WNV VNTs. They also revealed that the low specificity of IgG ELISA kits meant that it could detect animals infected with other flaviviruses. In contrast VNT and IgM ELISA assays were highly specific and did not detect antibodies against related flaviviruses. These results argue in favour of the need for and development of new, specific serological diagnostic assays that could be easily transferred to partner laboratories.

  20. A recombinant influenza A virus expressing domain III of West Nile virus induces protective immune responses against influenza and West Nile virus.

    Science.gov (United States)

    Martina, Byron E E; van den Doel, Petra; Koraka, Penelope; van Amerongen, Geert; Spohn, Gunther; Haagmans, Bart L; Provacia, Lisette B V; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2011-04-26

    West Nile virus (WNV) continues to circulate in the USA and forms a threat to the rest of the Western hemisphere. Since methods for the treatment of WNV infections are not available, there is a need for the development of safe and effective vaccines. Here, we describe the construction of a recombinant influenza virus expressing domain III of the WNV glycoprotein E (Flu-NA-DIII) and its evaluation as a WNV vaccine candidate in a mouse model. FLU-NA-DIII-vaccinated mice were protected from severe body weight loss and mortality caused by WNV infection, whereas control mice succumbed to the infection. In addition, it was shown that one subcutaneous immunization with 10(5) TCID(50) Flu-NA-DIII provided 100% protection against challenge. Adoptive transfer experiments demonstrated that protection was mediated by antibodies and CD4+T cells. Furthermore, mice vaccinated with FLU-NA-DIII developed protective influenza virus-specific antibody titers. It was concluded that this vector system might be an attractive platform for the development of bivalent WNV-influenza vaccines.

  1. A recombinant influenza A virus expressing domain III of West Nile virus induces protective immune responses against influenza and West Nile virus.

    Directory of Open Access Journals (Sweden)

    Byron E E Martina

    Full Text Available West Nile virus (WNV continues to circulate in the USA and forms a threat to the rest of the Western hemisphere. Since methods for the treatment of WNV infections are not available, there is a need for the development of safe and effective vaccines. Here, we describe the construction of a recombinant influenza virus expressing domain III of the WNV glycoprotein E (Flu-NA-DIII and its evaluation as a WNV vaccine candidate in a mouse model. FLU-NA-DIII-vaccinated mice were protected from severe body weight loss and mortality caused by WNV infection, whereas control mice succumbed to the infection. In addition, it was shown that one subcutaneous immunization with 10(5 TCID(50 Flu-NA-DIII provided 100% protection against challenge. Adoptive transfer experiments demonstrated that protection was mediated by antibodies and CD4+T cells. Furthermore, mice vaccinated with FLU-NA-DIII developed protective influenza virus-specific antibody titers. It was concluded that this vector system might be an attractive platform for the development of bivalent WNV-influenza vaccines.

  2. A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death.

    Science.gov (United States)

    Ma, Hongming; Dang, Ying; Wu, Yonggan; Jia, Gengxiang; Anaya, Edgar; Zhang, Junli; Abraham, Sojan; Choi, Jang-Gi; Shi, Guojun; Qi, Ling; Manjunath, N; Wu, Haoquan

    2015-07-28

    West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virus-induced cell death is poorly understood. Using a library containing 77,406 sgRNAs targeting 20,121 genes, we performed a genome-wide screen followed by a second screen with a sub-library. Among the genes identified, seven genes, EMC2, EMC3, SEL1L, DERL2, UBE2G2, UBE2J1, and HRD1, stood out as having the strongest phenotype, whose knockout conferred strong protection against WNV-induced cell death with two different WNV strains and in three cell lines. Interestingly, knockout of these genes did not block WNV replication. Thus, these appear to be essential genes that link WNV replication to downstream cell death pathway(s). In addition, the fact that all of these genes belong to the ER-associated protein degradation (ERAD) pathway suggests that this might be the primary driver of WNV-induced cell death. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Transposons and integrons in colistin-resistant clones of Klebsiella pneumoniae and Acinetobacter baumannii with epidemic or sporadic behaviour.

    Science.gov (United States)

    Arduino, Sonia M; Quiroga, María Paula; Ramírez, María Soledad; Merkier, Andrea Karina; Errecalde, Laura; Di Martino, Ana; Smayevsky, Jorgelina; Kaufman, Sara; Centrón, Daniela

    2012-10-01

    Multiple transposons, integrons and carbapenemases were found in Klebsiella pneumoniae colistin-resistant isolates as well as a genomic resistance island of the AbaR type in Acinetobacter baumannii colistin-resistant isolates from different hospitals from Buenos Aires City. PFGE analysis showed a polyclonal dissemination of antimicrobial resistance mechanisms among K. pneumoniae isolates, while in A. baumannii isolates the epidemic clone 1 from South America was found. Resistance determinants associated with horizontal gene transfer are contributing to the evolution to pandrug resistance in both epidemic and sporadic clones.

  4. A statistical study of sporadic sodium layer observed by Sodium lidar at Hefei (31.8° N, 117.3° E

    Directory of Open Access Journals (Sweden)

    X.-K. Dou

    2009-06-01

    Full Text Available Sodium lidar observations of sporadic sodium layers (SSLs during the past 3 years at a mid-latitude location (Hefei, China, 31.8° N, 117.3° E are reported in this paper. From 64 SSL events detected in about 900 h of observation, an SSL occurrence rate of 1 event every 14 h at our location was obtained. This result, combined with previous studies, reveals that the SSL occurrence can be relatively frequent at some mid-latitude locations. Statistical analysis of main parameters for the 64 SSL events was performed. By examining the corresponding data from an ionosonde, a considerable correlation was found with a Pearson coefficient of 0.66 between seasonal variations of SSL and those of sporadic E (Es during nighttime, which was in line with the research by Nagasawa and Abo (1995. From comparison between observations from the University of Science and Technology of China (USTC lidar and from Wuhan Institute of Physics and Mathematics (WIPM lidar (Wuhan, China, 31° N, 114° E, the minimum horizontal range for some events was estimated to be over 500 km.

  5. Surveillance for West Nile virus in clinic-admitted raptors, Colorado.

    Science.gov (United States)

    Nemeth, Nicole; Kratz, Gail; Edwards, Eric; Scherpelz, Judy; Bowen, Richard; Komar, Nicholas

    2007-02-01

    In 2005, 13.5% of clinic-admitted raptors in northern Colorado tested positive for West Nile virus (WNV). Clinic-admitted-raptor surveillance detected WNV activity nearly 14 weeks earlier than other surveillance systems. WNV surveillance using live raptor admissions to rehabilitation clinics may offer a novel surveillance method and should be considered along with other techniques already in use.

  6. West Nile virus replication requires fatty acid synthesis but is independent on phosphatidylinositol-4-phosphate lipids.

    Directory of Open Access Journals (Sweden)

    Miguel A Martín-Acebes

    Full Text Available West Nile virus (WNV is a neurovirulent mosquito-borne flavivirus, which main natural hosts are birds but it also infects equines and humans, among other mammals. As in the case of other plus-stranded RNA viruses, WNV replication is associated to intracellular membrane rearrangements. Based on results obtained with a variety of viruses, different cellular processes have been shown to play important roles on these membrane rearrangements for efficient viral replication. As these processes are related to lipid metabolism, fatty acid synthesis, as well as generation of a specific lipid microenvironment enriched in phosphatidylinositol-4-phosphate (PI4P, has been associated to it in other viral models. In this study, intracellular membrane rearrangements following infection with a highly neurovirulent strain of WNV were addressed by means of electron and confocal microscopy. Infection of WNV, and specifically viral RNA replication, were dependent on fatty acid synthesis, as revealed by the inhibitory effect of cerulenin and C75, two pharmacological inhibitors of fatty acid synthase, a key enzyme of this process. However, WNV infection did not induce redistribution of PI4P lipids, and PI4P did not localize at viral replication complex. Even more, WNV multiplication was not inhibited by the use of the phosphatidylinositol-4-kinase inhibitor PIK93, while infection by the enterovirus Coxsackievirus B5 was reduced. Similar features were found when infection by other flavivirus, the Usutu virus (USUV, was analyzed. These features of WNV replication could help to design specific antiviral approaches against WNV and other related flaviviruses.

  7. West Nile Virus Infection in American Singer Canaries: An Experimental Model in a Highly Susceptible Avian Species.

    Science.gov (United States)

    Hofmeister, Erik K; Lund, Melissa; Shearn Bochsler, Valerie

    2018-01-01

    This study investigated the susceptibility of American singer canaries ( Serinus canaria) to West Nile virus (WNV) infection. Adult canaries were inoculated with 10 5 , 10 2 , and 10 1 plaque forming units (PFU) of WNV. All birds became infected and mortality occurred by 5 days postinoculation. The load of viral RNA as determined by RT-qPCR was dose dependent, and was higher at all doses than the level of viral RNA detected in American crows ( Corvus brachyrhynchos) challenged with 10 5 PFU of WNV. In a subset of birds, viremia was detected by virus isolation; canaries inoculated with 10 1 PFU of WNV developed viremia exceeding 10 10 PFU/mL serum, a log higher than American crows inoculated with 10 5 PFU of virus. In canaries euthanized at 3 days postinoculation, WNV was isolated at >10 7 PFU of virus/100 mg of lung, liver, heart, spleen, and kidney tissues. Pallor of the liver and splenomegaly were the most common macroscopic observations and histologic lesions were most severe in liver, spleen, and kidney, particularly in canaries challenged with 10 2 and 10 1 PFU. Immunoreactivity to WNV was pronounced in the liver and spleen. IgG antibodies to WNV were detected in serum by enzyme immunoassay in 11 of 21 (52%) challenged canaries and, in 4 of 5 (20%) of these sera, neutralization antibodies were detected at a titer ≥ 1:20. American singer canaries provide a useful model as this bird species is highly susceptible to WNV infection.

  8. Nucleic acid amplification test for detection of west nile virus infection in pakistani blood donors

    International Nuclear Information System (INIS)

    Niazi, S.K.; Alam, M.

    2017-01-01

    Background: The study was planned to determine the presence of West Nile Virus (WNV) infection in Pakistani blood donors, using Nucleic Acid Amplification Test (NAT). Methods: The blood donors for study were selected on the basis of the standard questionnaire and routine screening results. Six donors were pooled using an automated pipettor and NAT for WNV was performed on Roche Cobas s 201 NAT system. The reactive pools were resolved in Individual Donation-NAT (ID-NAT) format and a sample from FFP bags of reactive donations was retrieved. NAT was again performed on retrieved plasma bag (RPB) sample to confirm the reactive donations. The donors were also recalled and interviewed about history of illness related to recent WNV infection. Results: After serological screening of 1929 donors during the study period, 1860 donors were selected for NAT test for WNV detection. The mean age of the donors was 28±8.77 (range: 18–57 years). 1847 (99.3%) donors were male and 13 (0.7%) were female. NAT for WNV identified six initially reactive pools (0.32%). On follow-up testing with RPB samples, 4 donors (0.21%) were found confirmed reactive for WNV RNA (NAT yield of 1 in 465 blood donors). Conclusion: WNV is a threat to safety of blood products in Pakistan. A screening strategy can be implemented after a large-scale study and financial considerations. One of the reduced cost screening strategies is seasonal screening of blood donors for WNV, with pooling of samples. (author)

  9. Experimental transmission of West Nile Virus and Rift Valley Fever Virus by Culex pipiens from Lebanon.

    Directory of Open Access Journals (Sweden)

    Renée Zakhia

    2018-01-01

    Full Text Available West Nile virus (WNV and Rift Valley fever virus (RVFV are two emerging arboviruses transmitted by Culex pipiens species that includes two biotypes: pipiens and molestus. In Lebanon, human cases caused by WNV and RVFV have never been reported. However, the introduction of these viruses in the country is likely to occur through the migratory birds and animal trades. In this study, we evaluated the ability of Cx. pipiens, a predominant mosquito species in urban and rural regions in Lebanon, to transmit WNV and RVFV. Culex egg rafts were collected in the West Bekaa district, east of Lebanon and adult females of Cx. pipiens were experimentally infected with WNV and RVFV Clone 13 strain at titers of 1.6×108 and 1.33×107 plaque forming units (PFU/mL, respectively. We estimated viral infection, dissemination and transmission at 3, 7, 14 and 19 days post infection (dpi. Results showed that infection was higher for WNV than for RVFV from 3 dpi to 19 dpi. Viral dissemination and transmission started from 3 dpi for WNV; and only from 19 dpi for RVFV. Moreover, Cx. pipiens were able to excrete in saliva a higher number of viral particles of WNV (1028 ± 405 PFU/saliva at 19 dpi than RVFV (42 PFU/saliva at 19 dpi. Cx. pipiens from Lebanon are efficient experimental vectors of WNV and to a lower extent, RVFV. These findings should stimulate local authorities to establish an active entomological surveillance in addition to animal surveys for both viruses in the country.

  10. Pathogenicity of two recent Western Mediterranean West Nile virus isolates in a wild bird species indigenous to Southern Europe: the red-legged partridge

    Directory of Open Access Journals (Sweden)

    Sotelo Elena

    2011-01-01

    Full Text Available Abstract West Nile virus (WNV is an emerging zoonotic pathogen whose geographic spread and incidence in humans, horses and birds has increased significantly in recent years. WNV has long been considered a mild pathogen causing self-limiting outbreaks. This notion has changed as WNV is causing large epidemics with a high impact on human and animal health. This has been particularly noteworthy since its introduction into North America in 1999. There, native bird species have been shown to be highly susceptible to WNV infection and disease with high mortalities. For this reason, the effect of WNV infection in North American bird species has been thoroughly studied by means of experimental inoculations in controlled trials. To a lesser extent, European wild birds have been shown to be affected clinically by WNV infection. Yet experimental studies on European wild bird species are lacking. The red-legged partridge (Alectoris rufa is a gallinaceous bird indigenous to the Iberian Peninsula, widely distributed in South Western Europe. It plays a key role in the Mediterranean ecosystem and constitutes an economically important game species. As such it is raised intensively in outdoor facilities. In this work, red-legged partridges were experimentally infected with two recent WNV isolates from the Western Mediterranean area: Morocco/2003 and Spain/2007. All inoculated birds became viremic and showed clinical disease, with mortality rates of 70% and 30%, respectively. These results show that Western Mediterranean WNV variants can be pathogenic for some European bird species, such as the red-legged partridge.

  11. West Nile virus infection in American singer canaries: An experimental model in a highly susceptible avian species

    Science.gov (United States)

    Hofmeister, Erik K.; Lund, Melissa; Shearn-Bochsler, Valerie I.

    2018-01-01

    This study investigated the susceptibility of American singer canaries (Serinus canaria) to West Nile virus (WNV) infection. Adult canaries were inoculated with 105, 102, and 101plaque forming units (PFU) of WNV. All birds became infected and mortality occurred by 5 days postinoculation. The load of viral RNA as determined by RT-qPCR was dose dependent, and was higher at all doses than the level of viral RNA detected in American crows (Corvus brachyrhynchos) challenged with 105 PFU of WNV. In a subset of birds, viremia was detected by virus isolation; canaries inoculated with 101 PFU of WNV developed viremia exceeding 1010 PFU/mL serum, a log higher than American crows inoculated with 105 PFU of virus. In canaries euthanized at 3 days postinoculation, WNV was isolated at >107 PFU of virus/100 mg of lung, liver, heart, spleen, and kidney tissues. Pallor of the liver and splenomegaly were the most common macroscopic observations and histologic lesions were most severe in liver, spleen, and kidney, particularly in canaries challenged with 102 and 101 PFU. Immunoreactivity to WNV was pronounced in the liver and spleen. IgG antibodies to WNV were detected in serum by enzyme immunoassay in 11 of 21 (52%) challenged canaries and, in 4 of 5 (20%) of these sera, neutralization antibodies were detected at a titer ≥ 1:20. American singer canaries provide a useful model as this bird species is highly susceptible to WNV infection.

  12. The Southern Argentina Agile Meteor Radar Orbital System (SAAMER-OS): An Initial Sporadic Meteoroid Orbital Survey in the Southern Sky

    Science.gov (United States)

    Janches, D.; Close, S.; Hormaechea, J. L.; Swarnalingam, N.; Murphy, A.; O'Connor, D.; Vandepeer, B.; Fuller, B.; Fritts, D. C.; Brunini, C.

    2015-01-01

    We present an initial survey in the southern sky of the sporadic meteoroid orbital environment obtained with the Southern Argentina Agile MEteor Radar (SAAMER) Orbital System (OS), in which over three-quarters of a million orbits of dust particles were determined from 2012 January through 2015 April. SAAMER-OS is located at the southernmost tip of Argentina and is currently the only operational radar with orbit determination capability providing continuous observations of the southern hemisphere. Distributions of the observed meteoroid speed, radiant, and heliocentric orbital parameters are presented, as well as those corrected by the observational biases associated with the SAAMER-OS operating parameters. The results are compared with those reported by three previous surveys performed with the Harvard Radio Meteor Project, the Advanced Meteor Orbit Radar, and the Canadian Meteor Orbit Radar, and they are in agreement with these previous studies. Weighted distributions for meteoroids above the thresholds for meteor trail electron line density, meteoroid mass, and meteoroid kinetic energy are also considered. Finally, the minimum line density and kinetic energy weighting factors are found to be very suitable for meteoroid applications. The outcomes of this work show that, given SAAMERs location, the system is ideal for providing crucial data to continuously study the South Toroidal and South Apex sporadic meteoroid apparent sources.

  13. Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

    Directory of Open Access Journals (Sweden)

    D. M. Heijink

    2007-01-01

    Full Text Available Background: TNF-Related Apoptosis Inducing Ligand (TRAIL is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP. Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n = 20, colorectal adenomas (n = 66 and colorectal carcinomas (n = 44 using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome-associated adenomas and carcinomas. Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P = 0.02. Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P < 0.001. A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.

  14. Clinical and Genetic Aspects of Sporadic Non-Medullar Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    U Rumjanzeva

    2006-03-01

    Full Text Available The role of somatic mutations in sporadic thyroid cancer is unclear today. Probably they coming out as aetiological factors in carcinogenesis as well as, respectfully to many authors, can to participate in TC pathogenesis and to determine the clinical course and prognosis of the disease. For today as main oncogenes taking part in initiation of thyroid malignant tumors are considered: RET/PTC, TRK, PTEN, P53, RAS, MET, PPARγ. By means of genetic investigations scientists are trying to solve problems with thyroid cancer differentiated diagnostics (cytokeratin-19, cytokeratin-20, mesothelial cells antigen (Hector Battifora MEsotelial (cell or HBME-1, loss of heterozigitoty (LOH in short arm of 3 chromosome (gene VHL -von Hippel Lindau, 3р26. Recently in foreign literature appeared reports of activated mutations in gene BRAF which most frequently are occurred in melanoma and papillary TC. Prognosis of thyroid cancer may reflected by the LOH as a biological breakage as well as changes of tumor suppressive gene P53 which fraught with decrease of disease prognosis. Thus, both researchers and clinicians have many questions concerning the role of genome, particularly in order to precise of genetic abnormality influence on tumor growth and therefore for assessment of clinical prognosis and with aim to chose adequate treatment tactic in each case.

  15. Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics

    NARCIS (Netherlands)

    Cali, I.; Castellani, R.; Alshekhlee, A.; Cohen, Y.; Blevins, J.; Yuan, J.; Langeveld, J.P.M.; Parchi, P.; Safar, J.G.; Zou, W.Q.; Gambetti, P.

    2009-01-01

    Five phenotypically distinct subtypes have been identified in sporadic Creutzfeldt-Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (PrP) gene and the presence of either one of the two protease K-resistant scrapie prion protein (PrPSc) types

  16. Globalization, land use and the invasion of West Nile virus

    Science.gov (United States)

    Kilpatrick, A. Marm

    2012-01-01

    Many invasive species that have been spread through the globalization of trade and travel are infectious pathogens. A paradigmatic case is the introduction of West Nile virus (WNV) into North America in 1999. A decade of research on the ecology and evolution of WNV includes three findings that provide insight into the outcome of future viral introductions. First, WNV transmission in North America is highest in urbanized and agricultural habitats, in part because the hosts and vectors of WNV are abundant in human-modified areas. Second, after its introduction, the virus quickly adapted to infect local mosquito vectors more efficiently than the originally introduced strain. Third, highly focused feeding patterns of the mosquito vectors of WNV result in unexpected host species being important for transmission. These findings provide a framework for predicting and preventing the emergence of foreign vector-borne pathogens. PMID:22021850

  17. Temperature, viral genetics, and the transmission of West Nile virus by Culex pipiens mosquitoes.

    Directory of Open Access Journals (Sweden)

    A Marm Kilpatrick

    2008-06-01

    Full Text Available The distribution and intensity of transmission of vector-borne pathogens can be strongly influenced by the competence of vectors. Vector competence, in turn, can be influenced by temperature and viral genetics. West Nile virus (WNV was introduced into the United States of America in 1999 and subsequently spread throughout much of the Americas. Previously, we have shown that a novel genotype of WNV, WN02, first detected in 2001, spread across the US and was more efficient than the introduced genotype, NY99, at infecting, disseminating, and being transmitted by Culex mosquitoes. In the current study, we determined the relationship between temperature and time since feeding on the probability of transmitting each genotype of WNV. We found that the advantage of the WN02 genotype increases with the product of time and temperature. Thus, warmer temperatures would have facilitated the invasion of the WN02 genotype. In addition, we found that transmission of WNV accelerated sharply with increasing temperature, T, (best fit by a function of T(4 showing that traditional degree-day models underestimate the impact of temperature on WNV transmission. This laboratory study suggests that both viral evolution and temperature help shape the distribution and intensity of transmission of WNV, and provides a model for predicting the impact of temperature and global warming on WNV transmission.

  18. Does the survival motor neuron copy number variation play a role in the onset and severity of sporadic amyotrophic lateral sclerosis in Malians?

    Directory of Open Access Journals (Sweden)

    Modibo Sangare

    2016-06-01

    Conclusion: Because of the short survival time of our patients, family histories and sample DNA for testing were not done. However, our results show that sporadic ALS is of earlier onset and shorter survival time as compared to patients elsewhere. We plan to establish a network of neurologists and researchers for early screening of ALS.

  19. Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Karch, André; Hermann, Peter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep; Zafar, Saima; Llorens, Franc; Müller-Heine, Annika; Zerr, Inga

    2015-05-01

    The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. [Lung transplantation in sporadic lymphangioleiomyomatosis: study of 7 cases].

    Science.gov (United States)

    Ansótegui Barrera, Emilio; Mancheño Franch, Nuria; Peñalver Cuesta, Juan Carlos; Vera-Sempere, Francisco; Padilla Alarcón, José

    2013-10-19

    Sporadic lymphangioleiomyomatosis (S-LAM) is a rare disease that affects only women. It is characterized by an abnormal proliferation of immature smooth muscle cells (LAM cells) that grow in an aberrant manner in the airway, parenchymal lung lymph and blood vessels, determining the onset of pulmonary cystic lesions. The disease has no treatment, progressing to respiratory failure, and lung transplantation (LT) may be a treatment option at this stage. Our goal was to study 7 patients undergoing LT for S-LAM. We studied a series of clinical and demographic characteristics, diagnostic modality and post-transplant outcomes. We performed a descriptive analysis of the series. The Kaplan-Meier method was used to estimate survival. The mean age of onset of symptoms was 35 years, the diagnosis of 37 years and that of LT 38 years. The most common symptom was dyspnea. Four patients had a history of pneumothorax and pleural effusion. The mean forced expiratory volume in one second was 32.7% and the diffusing capacity for carbon monoxide was 29%. All patients were subjected to LT and survival was 100, 85.7 and 57.1% at one, 3 and 5 years, respectively. Three died of bronchiolitis obliterans and 2 necropsies did not show evidence of disease recurrence. LT is a therapeutic option in patients with S-LAM with an advanced respiratory functional impairment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. Peripheral Tissue Involvement in Sporadic, Iatrogenic, and Variant Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Head, Mark W.; Ritchie, Diane; Smith, Nadine; McLoughlin, Victoria; Nailon, William; Samad, Sazia; Masson, Stephen; Bishop, Matthew; McCardle, Linda; Ironside, James W.

    2004-01-01

    Human prion diseases are rare fatal neurodegenerative conditions that occur as acquired, familial, or idiopathic disorders. A key event in their pathogenesis is the accumulation of an altered form of the prion protein, termed PrPSc, in the central nervous system. A novel acquired human prion disease, variant Creutzfeldt-Jakob disease, is thought to result from oral exposure to the bovine spongiform encephalopathy agent. This disease differs from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. We have used immunohistochemistry and Western blot techniques to analyze the tissue distribution and biochemical properties of PrPSc in peripheral tissues in a unique series of nine cases of variant Creutzfeldt-Jakob disease. We have compared this with the distribution and biochemical forms found in all of the major subtypes of sporadic Creutzfeldt-Jakob disease and in a case of iatrogenic Creutzfeldt-Jakob disease associated with growth hormone therapy. The results show that involvement of the lymphoreticular system is a defining feature of variant Creutzfeldt-Jakob disease, but that the biochemical isoform of PrPSc found is influenced by the cell type in which it accumulates. PMID:14695328

  2. Computed tomographic features of 23 sporadic cases with Legionella pneumophila pneumonia

    International Nuclear Information System (INIS)

    Yu Hui; Higa, Futoshi; Hibiya, Kenji; Furugen, Makoto; Sato, Yoko; Shinzato, Takashi; Haranaga, Shusaku; Yara, Satomi; Tateyama, Masao; Fujita, Jiro; Li, Huiping

    2010-01-01

    Objective: To describe the chest computed tomographic (CT) findings of Legionella pneumophila pneumonia. Methods: CT scans obtained from 23 sporadic cases of L. pneumophila pneumonia were retrospectively reviewed. Chest CT findings were analyzed with regard to the patterns and distributions of pulmonary abnormalities. We also analyzed the histopathology of lungs from guinea pigs with experimentally induced L. pneumophila pneumonia. Results: Consolidation and ground-glass opacity (GGO) were the main findings of CT scans in L. pneumophila pneumonia. The distribution of opacities was categorized as non-segmental (n = 20) and segmental (n = 4). Non-segmental distribution may follow an onset of segmental distribution. Pleural effusion was observed in 14 (58.3%) patients, of which 13 were accompanied with non-segmental distribution. Abscess formation was observed in only one immunocompromised patient. In the animal pneumonia model, the lesions comprised of terminal bronchioles, alveolar spaces, and interstitia. Small bacilli were observed to be contained by many macrophages within the alveoli. Conclusion: Non-segmental distribution was significantly more frequent than segmental distribution in L. pneumophila pneumonia. It is possible that L. pneumophila infection initially results in segmental pneumonia, which progresses to typical non-segmental distribution.

  3. Computed tomographic features of 23 sporadic cases with Legionella pneumophila pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Yu Hui [Department of Respiratory Diseases, Shanghai Pneumology Hospital, Tongji University, Shanghai (China); Higa, Futoshi; Hibiya, Kenji; Furugen, Makoto [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Sato, Yoko [Tomishiro Chuo Hospital, Okinawa (Japan); Shinzato, Takashi [Nakagami General Hospital, Okinawa (Japan); Haranaga, Shusaku; Yara, Satomi; Tateyama, Masao [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Fujita, Jiro, E-mail: fujita@med.u-ryukyu.ac.j [Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa (Japan); Li, Huiping [Department of Respiratory Diseases, Shanghai Pneumology Hospital, Tongji University, Shanghai (China)

    2010-06-15

    Objective: To describe the chest computed tomographic (CT) findings of Legionella pneumophila pneumonia. Methods: CT scans obtained from 23 sporadic cases of L. pneumophila pneumonia were retrospectively reviewed. Chest CT findings were analyzed with regard to the patterns and distributions of pulmonary abnormalities. We also analyzed the histopathology of lungs from guinea pigs with experimentally induced L. pneumophila pneumonia. Results: Consolidation and ground-glass opacity (GGO) were the main findings of CT scans in L. pneumophila pneumonia. The distribution of opacities was categorized as non-segmental (n = 20) and segmental (n = 4). Non-segmental distribution may follow an onset of segmental distribution. Pleural effusion was observed in 14 (58.3%) patients, of which 13 were accompanied with non-segmental distribution. Abscess formation was observed in only one immunocompromised patient. In the animal pneumonia model, the lesions comprised of terminal bronchioles, alveolar spaces, and interstitia. Small bacilli were observed to be contained by many macrophages within the alveoli. Conclusion: Non-segmental distribution was significantly more frequent than segmental distribution in L. pneumophila pneumonia. It is possible that L. pneumophila infection initially results in segmental pneumonia, which progresses to typical non-segmental distribution.

  4. High Prevalence of West Nile Virus in Domestic Birds and Detection in 2 New Mosquito Species in Madagascar.

    Science.gov (United States)

    Maquart, Marianne; Boyer, Sébastien; Rakotoharinome, Vincent Michel; Ravaomanana, Julie; Tantely, Michael Luciano; Heraud, Jean-Michel; Cardinale, Eric

    2016-01-01

    West Nile virus is an arthropod-borne zoonosis transmitted by a large number of mosquito species, and birds play a key role as reservoir of the virus. Its distribution is largely widespread over Africa, Asia, the Americas and Europe. Since 1978, it has frequently been reported in Madagascar. Studies described a high seroprevalence level of the virus in humans in different areas of the island and a human fatal case of WNV infection was reported in 2011. Despite these reports, the epidemiology of WNV in Madagascar, in particular, viral circulation remains unclear. To explore the transmission of WNV in two rural human populations of Madagascar, we investigated local mosquitoes and poultry for evidence of current infections, and determined seroprevalence of candidate sentinel species among the local poultry. These 2 areas are close to lakes where domestic birds, migratory wild birds and humans coexist. Serological analysis revealed WNV antibodies in domestic birds (duck, chicken, goose, turkey and guinea fowl) sampled in both districts (Antsalova 29.4% and Mitsinjo 16.7%). West Nile virus nucleic acid was detected in one chicken and in 8 pools of mosquitoes including 2 mosquito species (Aedeomyia madagascarica and Anopheles pauliani) that have not been previously described as candidate vectors for WNV. Molecular analysis of WNV isolates showed that all viruses detected were part of the lineage 2 that is mainly distributed in Africa, and were most closely matched by the previous Malagasy strains isolated in 1988. Our study showed that WNV circulates in Madagascar amongst domestic birds and mosquitoes, and highlights the utility of poultry as a surveillance tool to detect WNV transmission in a peri-domestic setting.

  5. Acute flaccid paralysis due to West nile virus infection in adults: A paradigm shift entity

    Directory of Open Access Journals (Sweden)

    Boby Varkey Maramattom

    2014-01-01

    Full Text Available Three cases of acute flaccid paralysis (AFP with preceding fever are described. One patient had a quadriparesis with a florid meningoencephalitic picture and the other two had asymmetric flaccid paralysis with fasciculations at the onset of illness. Magnetic resonance imaging in two cases showed prominent hyperintensitities in the spinal cord and brainstem with prominent involvement of the grey horn (polio-myelitis. Cerebrospinal fluid (CSF polymerase chain reaction was positive for West Nile virus (WNV in the index patient. All three cases had a positive WNV immunoglobulin M antibody in serum/CSF and significantly high titer of WNV neutralizing antibody in serum, clearly distinguishing the infection from other Flaviviridae such as Japanese encephalitis. WNV has been recognized in India for many decades; however, AFP has not been adequately described. WNV is a flavivirus that is spread by Culex mosquitoes while they take blood meals from humans and lineage 1 is capable of causing a devastating neuro-invasive disease with fatal consequences or severe morbidity. We describe the first three laboratory confirmed cases of WNV induced AFP from Kerala and briefly enumerate the salient features of this emerging threat.

  6. Spatio-temporal epidemiology of human West Nile virus disease in South Dakota.

    Science.gov (United States)

    Wimberly, Michael C; Giacomo, Paolla; Kightlinger, Lon; Hildreth, Michael B

    2013-10-29

    Despite a cold temperate climate and low human population density, the Northern Great Plains has become a persistent hot spot for human West Nile virus (WNV) disease in North America. Understanding the spatial and temporal patterns of WNV can provide insights into the epidemiological and ecological factors that influence disease emergence and persistence. We analyzed the 1,962 cases of human WNV disease that occurred in South Dakota from 2002-2012 to identify the geographic distribution, seasonal cycles, and interannual variability of disease risk. The geographic and seasonal patterns of WNV have changed since the invasion and initial epidemic in 2002-2003, with cases shifting toward the eastern portion of South Dakota and occurring earlier in the transmission season in more recent years. WNV cases were temporally autocorrelated at lags of up to six weeks and early season cumulative case numbers were correlated with seasonal totals, indicating the possibility of using these data for short-term early detection of outbreaks. Epidemiological data are likely to be most effective for early warning of WNV virus outbreaks if they are integrated with entomological surveillance and environmental monitoring to leverage the strengths and minimize the weaknesses of each information source.

  7. Survival analysis, long-term outcomes, and percentage of recovery up to 8 years post-infection among the Houston West Nile virus cohort.

    Directory of Open Access Journals (Sweden)

    Kristy O Murray

    Full Text Available In 2012, we witnessed a resurgence of West Nile virus (WNV in the United States, with the largest outbreak of human cases reported since 2003. WNV is now endemic and will continue to produce epidemics over time, therefore defining the long-term consequences of WNV infection is critical. Over a period of eight years, we prospectively followed a cohort of 157 WNV-infected subjects in the Houston metropolitan area to observe recovery over time and define the long-term clinical outcomes. We used survival analysis techniques to determine percentage of recovery over time and the effects of demographic and co-morbid conditions on recovery. We found that 40% of study participants continued to experience symptoms related to their WNV infection up to 8 years later. Having a clinical presentation of encephalitis and being over age 50 were significantly associated with prolonged or poor recovery over time. Since the health and economic impact as a result of prolonged recovery, continued morbidity, and related disability is likely substantial in those infected with WNV, future research should be aimed at developing effective vaccines to prevent illness and novel therapeutics to minimize morbidity, mortality, and long-term complications from infection.

  8. West Nile virus infection in horses, Indian ocean.

    Science.gov (United States)

    Cardinale, E; Bernard, C; Lecollinet, S; Rakotoharinome, V M; Ravaomanana, J; Roger, M; Olive, M M; Meenowa, D; Jaumally, M R; Melanie, J; Héraud, J M; Zientara, S; Cêtre-Sossah, C

    2017-08-01

    The circulation of West Nile virus (WNV) in horses was investigated in the Southwest Indian ocean. In 2010, blood samples were collected from a total of 303 horses originating from Madagascar, Mauritius, Reunion and the Seychelles and tested for WNV-specific antibodies. An overall seroprevalence of 27.39% was detected in the Indian Ocean with the highest WNV antibody prevalence of 46.22% (95% CI: [37.4-55.2%]) in Madagascar. The age and origin of the horses were found to be associated with the WNV infection risk. This paper presents the first seroprevalence study investigating WN fever in horses in the Southwest Indian Ocean area and indicates a potential risk of infection for humans and animals. In order to gain a better understanding of WN transmission cycles, WNV surveillance needs to be implemented in each of the countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. No evidence of somatic aryl hydrocarbon receptor interacting protein mutations in sporadic endocrine neoplasia

    DEFF Research Database (Denmark)

    Raitila, A; Georgitsi, M; Karhu, A

    2007-01-01

    . Here, we have analyzed 32 pituitary adenomas and 79 other tumors of the endocrine system for somatic AIP mutations by direct sequencing. No somatic mutations were identified. However, two out of nine patients with prolactin-producing adenoma were shown to harbor a Finnish founder mutation (Q14X...... as non-secreting pituitary adenomas have been reported, most mutation-positive patients have had growth hormone-producing adenomas diagnosed at relatively young age. Pituitary adenomas are also component tumors of some familial endocrine neoplasia syndromes such as multiple endocrine neoplasia type 1...... (MEN1) and Carney complex (CNC). Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes. Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas...

  10. Generation of an integration-free induced pluripotent stem cell line (CSC-43 from a patient with sporadic Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ana Marote

    2018-03-01

    Full Text Available An induced pluripotent stem cell (iPSC line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD. Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43 exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype. This iPSC line can be used to study the mechanisms underlying the development of PD.

  11. Four Sporadic Pediatric Cases of Yersinia enterocolitica O:8 Infection in a Rural Area of Japan.

    Science.gov (United States)

    Minami, Kisei; Yasuda, Ryu; Terakawa, Runa; Koike, Yumi; Takeuchi, Koichi; Higuchi, Tsukasa; Horiuchi, Ayaka; Kubota, Noriko; Hidaka, Eiko; Kawakami, Yoshiyuki

    2017-03-24

    In the spring of 2015, we experienced a cluster of 4 sporadic cases of yersiniosis in children in Nagano prefecture, a rural area of Japan. Two patients developed appendicitis-like episodes; one had acute gastroenteritis, and the other had bacteremia associated with liver abscess. The causative agent of these infections was Yersinia enterocolitica serogroup O:8. None of the patients had an underlying illness, and all have recovered completely. The patients were neither socially nor geographically related to each other. These 4 consecutive cases suggest that Y. enterocolitica O:8 has spread substantially in the middle part of Japan, and that this virulent strain might be more common than previously reported in our country.

  12. SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis

    Directory of Open Access Journals (Sweden)

    Bourdon Violaine

    2011-01-01

    Full Text Available Abstract Background Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic NF2 mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the SMARCB1 (INI1 tumor suppressor gene were described in familial and sporadic schwannomatosis patients. Methods To delineate the SMARCB1 gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas. Results Nine variants scattered along the sequence of SMARCB1 were identified. Five of them were classified as deleterious. All five patients carrying a SMARCB1 mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age. Conclusions These results suggest that patients with schwannomas have a significant probability of carrying a SMARCB1 mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the SMARCB1 gene.

  13. Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer’s Disease

    Science.gov (United States)

    Harris, Steven A.; Harris, Elizabeth A.

    2015-01-01

    Abstract This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer’s disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials. PMID

  14. Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999–2008

    Science.gov (United States)

    Hamaguchi, Tsuyoshi; Noguchi-Shinohara, Moeko; Nozaki, Ichiro; Nakamura, Yosikazu; Sato, Takeshi; Kitamoto, Tetsuyuki; Mizusawa, Hidehiro

    2009-01-01

    To elucidate the association between medical procedures and sporadic Creutzfeldt-Jakob disease (sCJD), we analyzed medical procedures (any surgical procedure, neurosurgery, ophthalmic surgery, and blood transfusion) for patients registered by the CJD Surveillance Committee in Japan during 1999–2008. We conducted an age-stratified case–control study with 753 sCJD patients and 210 controls and a study of patients who underwent neurosurgical or ophthalmic surgical procedures at the same hospital. Although the control group was relatively small, no evidence was found that prion disease was transmitted through the investigated medical procedures before onset of sCJD. After onset of sCJD, 4.5% of the sCJD patients underwent operations, including neurosurgical for 0.8% and ophthalmic for 1.9%; no special precautions against transmission of prion diseases were taken. Fortunately, we have not identified patients with prion disease attributed to these operations. Our findings indicate that surgical procedures or blood transfusion had little effect on the incidence of sCJD. PMID:19193271

  15. Laminar Distribution of the Pathological Changes in Sporadic and Variant Creutzfeldt-Jakob Disease

    Directory of Open Access Journals (Sweden)

    R. A. Armstrong

    2011-01-01

    Full Text Available The laminar distributions of the pathological changes in the cerebral cortex were compared in the prion diseases sporadic Creutzfeldt-Jakob disease (sCJD and variant CJD (vCJD. First, in some cortical regions, the vacuolation (“spongiform change” was more generally distributed across the cortex in sCJD. Second, there was greater neuronal loss in the upper cortex in vCJD and in the lower cortex in sCJD. Third, the “diffuse” and “florid” prion protein (PrPsc deposits were more frequently distributed in the upper cortex in vCJD and the “synaptic” deposits in the lower cortex in sCJD. Fourth, there was a significant gliosis mainly affecting the lower cortex of both disorders. The data suggest that the pattern of cortical degeneration is different in sCJD and vCJD which may reflect differences in aetiology and the subsequent spread of prion pathology within the brain.

  16. Comprehensive mapping of common immunodominant epitopes in the West Nile virus nonstructural protein 1 recognized by avian antibody responses.

    Directory of Open Access Journals (Sweden)

    Encheng Sun

    Full Text Available West Nile virus (WNV is a mosquito-borne flavivirus that primarily infects birds but occasionally infects humans and horses. Certain species of birds, including crows, house sparrows, geese, blue jays and ravens, are considered highly susceptible hosts to WNV. The nonstructural protein 1 (NS1 of WNV can elicit protective immune responses, including NS1-reactive antibodies, during infection of animals. The antigenicity of NS1 suggests that NS1-reactive antibodies could provide a basis for serological diagnostic reagents. To further define serological reagents for diagnostic use, the antigenic sites in NS1 that are targeted by host immune responses need to be identified and the potential diagnostic value of individual antigenic sites also needs to be defined. The present study describes comprehensive mapping of common immunodominant linear B-cell epitopes in the WNV NS1 using avian WNV NS1 antisera. We screened antisera from chickens, ducks and geese immunized with purified NS1 for reactivity against 35 partially overlapping peptides covering the entire WNV NS1. This study identified twelve, nine and six peptide epitopes recognized by chicken, duck and goose antibody responses, respectively. Three epitopes (NS1-3, 14 and 24 were recognized by antibodies elicited by immunization in all three avian species tested. We also found that NS1-3 and 24 were WNV-specific epitopes, whereas the NS1-14 epitope was conserved among the Japanese encephalitis virus (JEV serocomplex viruses based on the reactivity of avian WNV NS1 antisera against polypeptides derived from the NS1 sequences of viruses of the JEV serocomplex. Further analysis showed that the three common polypeptide epitopes were not recognized by antibodies in Avian Influenza Virus (AIV, Newcastle Disease Virus (NDV, Duck Plague Virus (DPV and Goose Parvovirus (GPV antisera. The knowledge and reagents generated in this study have potential applications in differential diagnostic approaches and

  17. Seasonal blood-feeding behavior of Culex tarsalis (Diptera: Culicidae) in Weld County, Colorado, 2007.

    Science.gov (United States)

    Kent, Rebekah; Juliusson, Lara; Weissmann, Michael; Evans, Sara; Komar, Nicholas

    2009-03-01

    Studies on Culex tarsalis Coquillett in Colorado have shown marked seasonal variation in the proportion of blood meals from birds and mammals. However, limitations in the specificity of antibodies used in the precipitin test and lack of vertebrate host availability data warrant revisiting Cx. tarsalis blood feeding behavior in the context of West Nile virus (WNV) transmission. We characterized the host preference of Cx. tarsalis during peak WNV transmission season in eastern Colorado and estimated the relative contribution of different avian species to WNV transmission. Cx. tarsalis preferred birds to mammals each month, although the proportion of blood meals from mammals increased in July and August. The distribution of blood meals differed significantly across months, in part because of changes in the proportion of blood meals from American robins, a preferred host. The estimated proportion of WNV-infectious vectors derived from American robins declined from 60 to 1% between June and August. The majority of avian blood meals came from doves, preferred hosts that contributed 25-40% of the WNV-infectious mosquitoes each month. Active WNV transmission was observed in association with a large house sparrow communal roost. These data show how seasonal patterns in Cx. tarsalis blood feeding behavior relate to WNV transmission in eastern Colorado, with the American robin contributing greatly to early-season virus transmission and a communal roost of sparrows serving as a focus for late-season amplification.

  18. Factors That Influence the Transmission of West Nile Virus in Florida.

    Science.gov (United States)

    Day, Jonathan F; Tabachnick, Walter J; Smartt, Chelsea T

    2015-09-01

    West Nile virus (WNV) was first detected in North America in New York City during the late summer of 1999 and was first detected in Florida in 2001. Although WNV has been responsible for widespread and extensive epidemics in human populations and epizootics in domestic animals and wildlife throughout North America, comparable epidemics have never materialized in Florida. Here, we review some of the reasons why WNV has yet to cause an extensive outbreak in Florida. The primary vector of mosquito-borne encephalitis virus in Florida is Culex nigripalpus Theobald. Rainfall, drought, and temperature are the primary factors that regulate annual populations of this species. Cx. nigripalpus is a competent vector of WNV, St. Louis encephalitis virus, and eastern equine encephalitis virus in Florida, and populations of this species can support focal amplification and transmission of these arboviruses. We propose that a combination of environmental factors influencing Cx. nigripalpus oviposition, blood-feeding behavior, and vector competence have limited WNV transmission in Florida to relatively small focal outbreaks and kept the state free of a major epidemic. Florida must remain vigilant to the danger from WNV, because a change in these environmental factors could easily result in a substantial WNV epidemic rivaling those seen elsewhere in the United States. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. 2014: A Record-Breaking Year for West Nile Virus Positive Mosquito Pools in Harris County and the City of Houston, Texas.

    Science.gov (United States)

    Randle, Yvonne H; Freeman, Cheryl Battle; Jackson, Monique; Reyna, Martin; Debboun, Mustapha

    2016-01-01

    In the 14 years since the emergence of West Nile virus (WNV) in Harris County and the city of Houston, Texas, the number of mosquitoes infected with the virus has fluctuated with several high and low count years. During this 14-year period, mosquito surveillance operational areas in Harris County were expanded from 248 to 268 and the distribution of the virus activity in mosquitoes varied from year to year. Operational areas with WNV infected mosquitoes increased from 137 in 2002 to 197 in 2006, decreased to 71 areas in 2007, and to an all-time low of 18 in 2008. The number increased to 78 areas in 2009, 96 in 2010, 133 in 2011, and 177 in 2012, but fell to 73 in 2013. However, 234 areas were confirmed in 2014, and only 138 in 2015. The WNV transmission was high in 2002 with 227 WNV positive mosquito pools. The number of positive mosquitoes remained elevated for a number of years and then declined from 2007 to 2010. Three record high years for WNV activity were: 2005, 2006, and 2011 with 698, 838, and 605 confirmed positive mosquito pools, respectively. Viral activity declined in 2012, followed by a marked decline in 2013 with only 147 WNV positive mosquito pools. In 2014, a record-breaking number of 1,286 WNV positive mosquito pools were confirmed in Harris County and the city of Houston, the most ever in a single season, while 406 were confirmed in 2015.

  20. Vaccination of mice using the West Nile virus E-protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects mice against a lethal challenge.

    Directory of Open Access Journals (Sweden)

    Marina De Filette

    Full Text Available West Nile virus (WNV is a mosquito-borne flavivirus that is endemic in Africa, the Middle East, Europe and the United States. There is currently no antiviral treatment or human vaccine available to treat or prevent WNV infection. DNA plasmid-based vaccines represent a new approach for controlling infectious diseases. In rodents, DNA vaccines have been shown to induce B cell and cytotoxic T cell responses and protect against a wide range of infections. In this study, we formulated a plasmid DNA vector expressing the ectodomain of the E-protein of WNV into nanoparticles by using linear polyethyleneimine (lPEI covalently bound to mannose and examined the potential of this vaccine to protect against lethal WNV infection in mice. Mice were immunized twice (prime--boost regime with the WNV DNA vaccine formulated with lPEI-mannose using different administration routes (intramuscular, intradermal and topical. In parallel a heterologous boost with purified recombinant WNV envelope (E protein was evaluated. While no significant E-protein specific humoral response was generated after DNA immunization, protein boosting of DNA-primed mice resulted in a marked increase in total neutralizing antibody titer. In addition, E-specific IL-4 T-cell immune responses were detected by ELISPOT after protein boost and CD8(+ specific IFN-γ expression was observed by flow cytometry. Challenge experiments using the heterologous immunization regime revealed protective immunity to homologous and virulent WNV infection.

  1. Survey for West Nile virus antibodies in wild ducks, 2004-06, USA

    Science.gov (United States)

    Hofmeister, Erik K.; Jankowski, Mark D.; Goldberg, Diana R.; Franson, J. Christian

    2016-01-01

    Detection of West Nile virus (WNV) in ducks has been reported in North America in isolated cases of mortality in wild waterbirds and following outbreaks in farmed ducks. Although the virus has been noted as an apparent incidental finding in several species of ducks, little is known about the prevalence of exposure or the outcome of infection with WNV in wild ducks in North America. From 2004–06, we collected sera from 1,406 wild-caught American Wigeon (Anas americana), Mallard (Anas platyrhynchos), and Northern Pintail (Anas acuta) ducks at national wildlife refuges (NWRs) in North Dakota and Wood Ducks (Aix sponsa) at NWRs in South Carolina and Tennessee. We measured the prevalence of previous exposure to WNV in these ducks by measuring WNV antibodies and evaluated variation in exposure among species, age, and year. Additionally, we evaluated the performance of a commercial antibody to wild bird immunoglobulin in duck species that varied in their phylogenetic relatedness to the bird species the antibody was directed against. As determined by a screening immunoassay and a confirmatory plaque reduction neutralization assay, the prevalence of WNV antibody was 10%. In light of experimental studies that show ducks to be relatively resistant to mortality caused by WNV, the antibody prevalence we detected suggests that wild ducks may be less-frequently exposed to WNV than expected for birds inhabiting wetlands where they may acquire infection from mosquitoes.

  2. THE SOUTHERN ARGENTINA AGILE METEOR RADAR ORBITAL SYSTEM (SAAMER-OS): AN INITIAL SPORADIC METEOROID ORBITAL SURVEY IN THE SOUTHERN SKY

    Energy Technology Data Exchange (ETDEWEB)

    Janches, D.; Swarnalingam, N. [Space Weather Laboratory, Mail Code 674, NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Close, S. [Space Environment and Satellite Systems Laboratory, Department of Aeronautics and Astronautics, Stanford University, Palo Alto, CA (United States); Hormaechea, J. L. [Estacion Astronomica Rio Grande, Rio Grande, Tierra del Fuego (Argentina); Murphy, A.; O’Connor, D.; Vandepeer, B.; Fuller, B. [Genesis Software Pty Ltd, Adelaide (Australia); Fritts, D. C. [GATS Inc., Boulder CO (United States); Brunini, C., E-mail: diego.janches@nasa.gov, E-mail: nimalan.swarnalingam@nasa.gov, E-mail: sigridc@stanford.edu, E-mail: jlhormaechea@untdf.edu.ar, E-mail: amurphy@gsoft.com.au, E-mail: doconnor@gsoft.com.au, E-mail: bvandepe@gsoft.com.au, E-mail: bfuller@gsoft.com.au, E-mail: dave@gats-inc.com, E-mail: claudiobrunini@yahoo.com [Departmento de Astronomia y Geofísica, Universidad Nacional de La Plata, La Plata (Argentina)

    2015-08-10

    We present an initial survey in the southern sky of the sporadic meteoroid orbital environment obtained with the Southern Argentina Agile MEteor Radar (SAAMER) Orbital System (OS), in which over three-quarters of a million orbits of dust particles were determined from 2012 January through 2015 April. SAAMER-OS is located at the southernmost tip of Argentina and is currently the only operational radar with orbit determination capability providing continuous observations of the southern hemisphere. Distributions of the observed meteoroid speed, radiant, and heliocentric orbital parameters are presented, as well as those corrected by the observational biases associated with the SAAMER-OS operating parameters. The results are compared with those reported by three previous surveys performed with the Harvard Radio Meteor Project, the Advanced Meteor Orbit Radar, and the Canadian Meteor Orbit Radar, and they are in agreement with these previous studies. Weighted distributions for meteoroids above the thresholds for meteor trail electron line density, meteoroid mass, and meteoroid kinetic energy are also considered. Finally, the minimum line density and kinetic energy weighting factors are found to be very suitable for meteroid applications. The outcomes of this work show that, given SAAMER’s location, the system is ideal for providing crucial data to continuously study the South Toroidal and South Apex sporadic meteoroid apparent sources.

  3. Molecular Cytogenetic Characterization Identified the Murine B-Cell Lymphoma Cell Line A-20 as a Model for Sporadic Burkitt's Lymphoma.

    Science.gov (United States)

    Guja, Karolina; Liehr, Thomas; Rincic, Martina; Kosyakova, Nadezda; Hussein Azawi, Shaymaa S

    2017-11-01

    Here, we report the first molecular cytogenetic characterization of the BALB/cAnN mouse derived B-cell non-Hodgkin lymphoma (B-cell NHL) cell lines A-20. Even though previously used as a model for testing of, for example, dexametason, up to present, no data in the genetic properties of A-20 were available. The present study closed this gap and provides evidence that A-20 is a model for B-cell NHL subgroup sporadic Burkitt's lymphoma. C-myc oncogene is involved in a translocation and copy number alterations as gain of murine 14q material could be observed. Interestingly, the cell line showed the karyotype 39,X,-X or -Y,t(2;15)(qE5;qD2),del(6)(qB3qC3),del(9)(qA3qA4),dup(14)(qE1qE4) in ~95% of the cells, being exceptionally stable for cell lines being established 38 years ago. Still, ~5% of the cells showed polyploidization followed by chromothripsis. It remains to be determined if this can be observed also in other cell lines, just has not been reported yet, and/or if it is a unique feature of A-20. Overall, finally here, the necessary genetic data to identify A-20 as a model for human sporadic Burkitt's lymphoma are provided.

  4. Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Yuwei Wang

    2014-01-01

    Full Text Available Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP. CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS and overall survival (OS were analyzed using Kaplan-Meier method (log-rank test and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50 of patients were characterized as CIMP positive. Univariate analysis showed stage III (P=0.049 and CIMP positive (P=0.014 patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P=0.019. In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P=0.023. Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy.

  5. DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes

    Czech Academy of Sciences Publication Activity Database

    Farkas, S. A.; Vymetálková, Veronika; Vodičková, Ludmila; Vodička, Pavel; Torbjörn, K. N.

    2014-01-01

    Roč. 6, č. 2 (2014), s. 179-191 ISSN 1750-1911 R&D Projects: GA ČR GPP304/11/P715; GA ČR(CZ) GAP304/12/1585; GA MZd NT14329 Institutional support: RVO:68378041 Keywords : CpG * DNA repair genes * sporadic colorectal cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.649, year: 2014

  6. Neuropsychological Symptoms in Sporadic Creutzfeldt-Jakob Disease Patients in Germany.

    Science.gov (United States)

    Krasnianski, Anna; Bohling, Geeske T; Heinemann, Uta; Varges, Daniela; Meissner, Bettina; Schulz-Schaeffer, Walter J; Reif, Andreas; Zerr, Inga

    2017-01-01

    The polymorphism at codon 129 of the prion protein gene (PRNP) and the PrPSc types 1 and 2 belong to a molecular classification of sporadic Creutzfeldt-Jakob disease (sCJD) that correlates well with the clinical and neuropathological phenotype of sCJD. The aim of the study was to perform the first detailed evaluation of neuropsychological deficits in a large group of definite sCJD patients with known molecular subtype. We analyzed neuropsychological symptoms in a cohort of 248 sCJD patients with known M129 V polymorphism of PRNP and prion protein type. Neuropsychological symptoms were very frequent in our patients (96%) and occurred as early as in the first third of the disease course. Besides amnesia and impaired attention (89% each), frontal lobe syndrome (75%), aphasia (63%), and apraxia (57%) were the most common neuropsychological deficits. There was no statistically significant difference with regard to frequency of neuropsychological symptoms between the subtypes. In MV2 and VV2 patients, the onset of neuropsychological symptoms was significantly later than in all other subtypes. We provide the first detailed analysis of neuropsychological symptoms in a large group of sCJD patients with known M129 V genotype and prion protein type. We suggest that the rate of progression of neuropsychological symptoms is subtype-specific. These data may improve the diagnosis in atypical sCJD subtypes.

  7. Experimental infection of rock pigeons (Columba livia) with three West Nile virus lineage 1 strains isolated in Italy between 2009 and 2012.

    Science.gov (United States)

    Spedicato, M; Carmine, I; Bellacicco, A L; Marruchella, G; Marini, V; Pisciella, M; Di Francesco, G; Lorusso, A; Monaco, F; Savini, G

    2016-04-01

    West Nile virus (WNV) circulation dynamics in the context of the urban environment is not yet elucidated. In this perspective, three groups of eight rock pigeons (Columbia livia) were inoculated with three WNV lineage 1 strains isolated in Italy between 2009 and 2012. The pigeons did not develop any clinical signs consistent with WNV acute infection. All animals seroconverted and shed virus up to 15 days post-infection by the oral or cloacal routes. In all infected groups viraemia lasted for 4 days post-infection. No WNV-specific gross or histological lesions were found in infected birds compared to control birds and immunohistochemistry remained constantly negative from all tissues. The reservoir competence index was also assessed and it ranged between 0·11 and 0·14. This study demonstrates that pigeons are competent reservoir hosts for Italian WNV lineage 1 circulating strains thus potentially posing a risk to the public health system.

  8. Experimental infection of cliff swallows (Petrochelidon pyrrhonota) with varying doses of West Nile virus

    Science.gov (United States)

    Oesterle, P.T.; Nemeth, N.M.; VanDalen, Kaci K.; Sullivan, H.; Bentler, K.T.; Young, G.R.; McLean, R.G.; Clark, L.; Smeraski, C.; Hall, Jeffrey S.

    2009-01-01

    Cliff swallows (Petrochelidon pyrrhonota) were inoculated with differing doses of West Nile virus (WNV) to evaluate their potential role as reservoir hosts in nature. Swallows often nest in large colonies in habitats and months associated with high mosquito abundance and early WNV transmission in North America. Additionally, cliff swallow diet consists of insects, including mosquitoes, leading to an additional potential route of WNV infection. The average peak viremia titer among infected cliff swallows was 106.3 plaque-forming units (PFU)/mL serum and the reservoir competence index was 0.34. There was no correlation between dose and probability of becoming infected or viremia peak and duration. Oral shedding was detected from 2 to 14 days post-inoculation with an average peak titer of 1044 PFU/swab. These results suggest that cliff swallows are competent reservoir hosts of WNV and therefore, they may play a role in early seasonal amplification and maintenance of WNV. Copyright ?? 2009 by The American Society of Tropical Medicine and Hygiene.

  9. Antibodies to West Nile virus in asymptomatic mammals, birds, and reptiles in the Yucatan Peninsula of Mexico.

    Science.gov (United States)

    Farfán-Ale, José A; Blitvich, Bradley J; Marlenee, Nicole L; Loroño-Pino, María A; Puerto-Manzano, Fernando; García-Rejón, Julián E; Rosado-Paredes, Elsy P; Flores-Flores, Luis F; Ortega-Salazar, Andres; Chávez-Medina, Jaidy; Cremieux-Grimaldi, Juan C; Correa-Morales, Favián; Hernández-Gaona, Gerson; Méndez-Galván, Jorge F; Beaty, Barry J

    2006-05-01

    Surveillance for evidence of West Nile virus (WNV) infection in taxonomically diverse vertebrates was conducted in the Yucatan Peninsula of Mexico in 2003 and 2004. Sera from 144 horses on Cozumel Island, Quintana Roo State, 415 vertebrates (257 birds, 52 mammals, and 106 reptiles) belonging to 61 species from the Merida Zoo, Yucatan State, and 7 farmed crocodiles in Ciudad del Carmen, Campeche State were assayed for antibodies to flaviviruses. Ninety (62%) horses on Cozumel Island had epitope-blocking enzyme-linked immunosorbent assay (ELISA) antibodies to flaviviruses, of which 75 (52%) were seropositive for WNV by plaque reduction neutralization test (PRNT). Blocking ELISA antibodies to flaviviruses also were detected in 13 (3%) animals in the Merida Zoo, including 7 birds and 2 mammals (a jaguar and coyote) seropositive for WNV by PRNT. Six (86%) crocodiles in Campeche State had PRNT-confirmed WNV infections. All animals were healthy at the time of serum collections and none had a history of WNV-like illness.

  10. [Birds, mosquitoes and West Nile virus: little risk of West Nile fever in the Netherlands].

    Science.gov (United States)

    Duijster, Janneke W; Stroo, C J Arjan; Braks, Marieta A H

    2016-01-01

    Due to increased incidence of West Nile fever (WNF) in Europe and the rapid spread of West Nile virus (WNV) in the US, it is commonly thought that it will only be a matter of time before WNV reaches the Netherlands. However, assessing whether WNV is really a threat to the Dutch population is challenging, due to the numerous factors affecting transmission of the virus. Some of these factors are known to limit the risk of WNF in the Netherlands. This risk is determined by the interaction between the pathogen (WNV), the vectors (Culex mosquitoes), the reservoirs (birds) and the exposure of humans to infected mosquitoes. In this paper, we discuss the factors influencing introduction, establishment and spread of WNV in the Netherlands. The probability that each of these three phases will occur in the Netherlands is currently relatively small, as is the risk of WNF infection in humans in the Netherlands.

  11. Evolutionary relationship between Old World West Nile virus strains Evidence for viral gene flow between africa, the middle east, and europe

    International Nuclear Information System (INIS)

    Charrel, R.N.; Brault, A.C.; Gallian, P.; Lemasson, J.-J.; Murgue, B.; Murri, S.; Pastorino, B.; Zeller, H.; Chesse, R. de; Micco, P. de; Lamballerie, X. de

    2003-01-01

    Little is known about the genetic relationships between European and other Old-World strains of West Nile virus (WNV) and persistence of WNV North of Mediterranean. We characterized the complete genomes of three WNV strains from France (horse-2000), Tunisia (human-1997) and Kenya (mosquito-1998), and the envelope, NS3 and NS5 genes of the Koutango virus. Phylogenetic analyses including all available full-length sequences showed that: (1) Koutango virus is a distant variant of WNV; (2) the three characterized strains belong to lineage 1, clade 1a; (3) the Tunisian strain roots the lineage of viruses introduced in North America. We established that currently available partial envelope sequences do not generate reliable phylogenies. Accordingly, establishing a large WNV sequence database is pivotal for the understanding of spatial and temporal epidemiology of this virus. For rapid completion of that purpose, colinearized E-NS3-NS5 gene sequences were shown to constitute a valuable surrogate for complete sequences

  12. Climate change projections of West Nile virus infections in Europe: implications for blood safety practices.

    Science.gov (United States)

    Semenza, Jan C; Tran, Annelise; Espinosa, Laura; Sudre, Bertrand; Domanovic, Dragoslav; Paz, Shlomit

    2016-03-08

    West Nile virus (WNV) is transmitted by mosquitoes in both urban as well as in rural environments and can be pathogenic in birds, horses and humans. Extrinsic factors such as temperature and land use are determinants of WNV outbreaks in Europe, along with intrinsic factors of the vector and virus. With a multivariate model for WNV transmission we computed the probability of WNV infection in 2014, with July 2014 temperature anomalies. We applied the July temperature anomalies under the balanced A1B climate change scenario (mix of all energy sources, fossil and non-fossil) for 2025 and 2050 to model and project the risk of WNV infection in the future. Since asymptomatic infections are common in humans (which can result in the contamination of the donated blood) we estimated the predictive prevalence of WNV infections in the blood donor population. External validation of the probability model with 2014 cases indicated good prediction, based on an Area Under Curve (AUC) of 0.871 (SD = 0.032), on the Receiver Operating Characteristic Curve (ROC). The climate change projections for 2025 reveal a higher probability of WNV infection particularly at the edges of the current transmission areas (for example in Eastern Croatia, Northeastern and Northwestern Turkey) and an even further expansion in 2050. The prevalence of infection in (blood donor) populations in the outbreak-affected districts is expected to expand in the future. Predictive modelling of environmental and climatic drivers of WNV can be a valuable tool for public health practice. It can help delineate districts at risk for future transmission. These areas can be subjected to integrated disease and vector surveillance, outreach to the public and health care providers, implementation of personal protective measures, screening of blood donors, and vector abatement activities.

  13. 4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression.

    Science.gov (United States)

    Shives, Katherine D; Massey, Aaron R; May, Nicholas A; Morrison, Thomas E; Beckham, J David

    2016-10-18

    West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7 GpppN m 5' cap with 2'- O -methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4EBP) pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E) interaction and eukaryotic initiation factor 4F (eIF4F) complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6) and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome.

  14. 4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression

    Directory of Open Access Journals (Sweden)

    Katherine D. Shives

    2016-10-01

    Full Text Available West Nile virus (WNV is a (+ sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7GpppNm 5′ cap with 2′-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1 for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K and eukaryotic translation initiation factor 4E-binding protein (4EBP pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E interaction and eukaryotic initiation factor 4F (eIF4F complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6 and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome.

  15. Experimental evolution of an RNA virus in wild birds: evidence for host-dependent impacts on population structure and competitive fitness.

    Directory of Open Access Journals (Sweden)

    Nathan D Grubaugh

    2015-05-01

    Full Text Available Within hosts, RNA viruses form populations that are genetically and phenotypically complex. Heterogeneity in RNA virus genomes arises due to error-prone replication and is reduced by stochastic and selective mechanisms that are incompletely understood. Defining how natural selection shapes RNA virus populations is critical because it can inform treatment paradigms and enhance control efforts. We allowed West Nile virus (WNV to replicate in wild-caught American crows, house sparrows and American robins to assess how natural selection shapes RNA virus populations in ecologically relevant hosts that differ in susceptibility to virus-induced mortality. After five sequential passages in each bird species, we examined the phenotype and population diversity of WNV through fitness competition assays and next generation sequencing. We demonstrate that fitness gains occur in a species-specific manner, with the greatest replicative fitness gains in robin-passaged WNV and the least in WNV passaged in crows. Sequencing data revealed that intrahost WNV populations were strongly influenced by purifying selection and the overall complexity of the viral populations was similar among passaged hosts. However, the selective pressures that control WNV populations seem to be bird species-dependent. Specifically, crow-passaged WNV populations contained the most unique mutations (~1.7× more than sparrows, ~3.4× more than robins and defective genomes (~1.4× greater than sparrows, ~2.7× greater than robins, but the lowest average mutation frequency (about equal to sparrows, ~2.6× lower than robins. Therefore, our data suggest that WNV replication in the most disease-susceptible bird species is positively associated with virus mutational tolerance, likely via complementation, and negatively associated with the strength of selection. These differences in genetic composition most likely have distinct phenotypic consequences for the virus populations. Taken together

  16. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Directory of Open Access Journals (Sweden)

    Kelsey Roe

    Full Text Available Characterizing the mechanisms by which West Nile virus (WNV causes blood-brain barrier (BBB disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE. Infection with WNV (NY99 strain significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1 did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101 strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  17. Seroprevalence of West Nile Virus in feral horses on Sheldon National Wildlife Refuge, Nevada, United States

    Science.gov (United States)

    Franson, J. Christian; Hofmeister, Erik K.; Collins, Gail H.; Dusek, Robert J.

    2011-01-01

    We screened 1,397 feral horses (Equus caballus) on Sheldon National Wildlife Refuge, Nevada, United States, for IgM and IgG against flavivirus during 2004–2006, 2008, and 2009. Positive serum samples were tested for neutralizing antibodies to West Nile virus (WNV) and St. Louis encephalitis virus (SLEV). One animal was positive for antibody against WNV in 2004, but all others tested in 2004–2006 were negative. In 2008 and 2009, we found evidence of increasing seropositive horses with age, whereas seroprevalence of WNV decreased from 19% in 2008 to 7.2% in 2009. No horses were positive for antibody against SLEV. Being unvaccinated, feral horses can be useful for WNV surveillance.

  18. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Es, M.A. van; Veldink, J.H.; Saris, C.G.J.; Blauw, H.M.; Vught, P.W. van; Birve, A.; Lemmens, R.; Schelhaas, H.J.; Groen, E.J.; Huisman, M.H.; Kooi, A.J. van der; Visser, M. de; Dahlberg, C.; Estrada, K.; Rivadeneira, F.; Hofman, A.; Zwarts, M.J.; Doormaal, P.T. van; Rujescu, D.; Strengman, E.; Giegling, I.; Muglia, P.; Tomik, B.; Slowik, A.; Uitterlinden, A.G.; Hendrich, C.; Waibel, S.; Meyer, T.; Ludolph, A.C.; Glass, J.D.; Purcell, S.; Cichon, S.; Nothen, Markus; Wichmann, H.E.; Schreiber, S.; Vermeulen, S.; Kiemeney, L.A.L.M.; Wokke, J.H.J.; Cronin, S.; McLaughlin, R.L.; Hardiman, O.; Fumoto, K.; Pasterkamp, R.J.; Meininger, V.; Melki, J.; Leigh, P.N.; Shaw, C.E.; Landers, J.E.; Al-Chalabi, A.; Brown Jr., R.H.; Robberecht, W.; Andersen, P.M.; Ophoff, R.A.; Berg, L.H. van den

    2009-01-01

    We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide

  19. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Es, Michael A.; Veldink, Jan H.; Saris, Christiaan G. J.; Blauw, Hylke M.; van Vught, Paul W. J.; Birve, Anna; Lemmens, Robin; Schelhaas, Helenius J.; Groen, Ewout J. N.; Huisman, Mark H. B.; van der Kooi, Anneke J.; de Visser, Marianne; Dahlberg, Caroline; Estrada, Karol; Rivadeneira, Fernando; Hofman, Albert; Zwarts, Machiel J.; van Doormaal, Perry T. C.; Rujescu, Dan; Strengman, Eric; Giegling, Ina; Muglia, Pierandrea; Tomik, Barbara; Slowik, Agnieszka; Uitterlinden, Andre G.; Hendrich, Corinna; Waibel, Stefan; Meyer, Thomas; Ludolph, Albert C.; Glass, Jonathan D.; Purcell, Shaun; Cichon, Sven; Nöthen, Markus M.; Wichmann, H.-Erich; Schreiber, Stefan; Vermeulen, Sita H. H. M.; Kiemeney, Lambertus A.; Wokke, John H. J.; Cronin, Simon; McLaughlin, Russell L.; Hardiman, Orla; Fumoto, Katsumi; Pasterkamp, R. Jeroen; Meininger, Vincent; Melki, Judith; Leigh, P. Nigel; Shaw, Christopher E.; Landers, John E.; Al-Chalabi, Ammar; Brown, Robert H.; Robberecht, Wim; Andersen, Peter M.; Ophoff, Roel A.; van den Berg, Leonard H.

    2009-01-01

    We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P <1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide

  20. Association between the PRNP 1368 polymorphism and the occurrence of sporadic Creutzfeldt-Jakob disease

    Science.gov (United States)

    Bratosiewicz-Wąsik, Jolanta; Smoleń-Dzirba, Joanna; Rozemuller, Annemieke J.; Jansen, Casper; Spliet, Wim; Jansen, Gerard H.; Wąsik, Tomasz J.; Liberski, Paweł P.

    2012-01-01

    Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. The etiology of sporadic form of CJD remains unsolved. In addition to the codon 129 polymorphism, polymorphisms in the non-coding region of PRNP are considered as important factors in sCJD development. To assess a possible association between PRNP 1368 SNP and sCJD, we compared the genotype, allele and haplotype frequencies of the 1368 SNP among 46 sCJD patients of Dutch origin with the respective frequencies in healthy controls. We detected a significant association between sCJD and 1368T/T genotype. A significant difference was also observed in 1368 alleles’ distribution. In the haplotype analysis, haplotype 1368C-129G was associated with decreased risk of sCJD in Dutch population. Our findings support the hypothesis that genetic variations in the regulatory region of the PRNP gene may influence the pathogenesis of sCJD. PMID:22895088

  1. Haplotype defined by the MLH1-93G/A polymorphism is associated with MLH1 promoter hypermethylation in sporadic colorectal cancers.

    Science.gov (United States)

    Miyakura, Yasuyuki; Tahara, Makiko; Lefor, Alan T; Yasuda, Yoshikazu; Sugano, Kokichi

    2014-11-24

    Methylation of the MLH1 promoter region has been suggested to be a major mechanism of gene inactivation in sporadic microsatellite instability-positive (MSI-H) colorectal cancers (CRCs). Recently, single-nucleotide polymorphism (SNP) in the MLH1 promoter region (MLH1-93G/A; rs1800734) has been proposed to be associated with MLH1 promoter methylation, loss of MLH1 protein expression and MSI-H tumors. We examined the association of MLH1-93G/A and six other SNPs surrounding MLH1-93G/A with the methylation status in 210 consecutive sporadic CRCs in Japanese patients. Methylation of the MLH1 promoter region was evaluated by Na-bisulfite polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. The genotype frequencies of SNPs located in the 54-kb region surrounding the MLH1-93G/A SNP were examined by SSCP analysis. Methylation of the MLH1 promoter region was observed in 28.6% (60/210) of sporadic CRCs. The proportions of MLH1-93G/A genotypes A/A, A/G and G/G were 26% (n=54), 51% (n=108) and 23% (n=48), respectively, and they were significantly associated with the methylation status (p=0.01). There were no significant associations between genotype frequency of the six other SNPs and methylation status. The A-allele of MLH1-93G/A was more common in cases with methylation than the G-allele (p=0.0094), especially in females (p=0.0067). In logistic regression, the A/A genotype of the MLH1-93G/A SNP was shown to be the most significant risk factor for methylation of the MLH1 promoter region (odds ratio 2.82, p=0.003). Furthermore, a haplotype of the A-allele of rs2276807 located -47 kb upstream from the MLH1-93G/A SNP and the A-allele of MLH1-93G/A SNP was significantly associated with MLH1 promoter methylation. These results indicate that individuals, and particularly females, carrying the A-allele at the MLH1-93G/A SNP, especially in association with the A-allele of rs2276807, may harbor an increased risk of methylation of the MLH1 promoter

  2. West Nile Virus State of the Art Report of MALWEST Project

    Science.gov (United States)

    Marka, Andriani; Diamantidis, Alexandros; Papa, Anna; Valiakos, George; Chaintoutis, Serafeim C.; Doukas, Dimitrios; Tserkezou, Persefoni; Giannakopoulos, Alexios; Papaspyropoulos, Konstantinos; Patsoula, Eleni; Badieritakis, Evangelos; Baka, Agoritsa; Tseroni, Maria; Pervanidou, Danai; Papadopoulos, Nikos T.; Koliopoulos, George; Tontis, Dimitrios; Dovas, Chrysostomos I.; Billinis, Charalambos; Tsakris, Athanassios; Kremastinou, Jenny; Hadjichristodoulou, Christos

    2013-01-01

    During the last three years Greece is experiencing the emergence of West Nile virus (WNV) epidemics. Within this framework, an integrated surveillance and control programme (MALWEST project) with thirteen associate partners was launched aiming to investigate the disease and suggest appropriate interventions. One out of seven work packages of the project is dedicated to the State of the Art report for WNV. Three expert working groups on humans, animals and mosquitoes were established. Medical databases (PubMed, Scopus) were searched together with websites: e.g., WHO, CDC, ECDC. In total, 1,092 relevant articles were initially identified and 258 of them were finally included as references regarding the current knowledge about WNV, along with 36 additional sources (conference papers, reports, book chapters). The review is divided in three sections according to the fields of interest: (1) WNV in humans (epidemiology, molecular characteristics, transmission, diagnosis, treatment, prevention, surveillance); (2) WNV in animals (epidemiological and transmission characteristics concerning birds, horses, reptiles and other animal species) and (3) WNV in mosquitoes (control, surveillance). Finally, some examples of integrated surveillance programmes are presented. The introduction and establishment of the disease in Greece and other European countries further emphasizes the need for thorough research and broadening of our knowledge on this viral pathogen. PMID:24317379

  3. West Nile Virus Seroprevalence in the Greek Population in 2013: A Nationwide Cross-Sectional Survey

    Science.gov (United States)

    Hadjichristodoulou, Christos; Pournaras, Spyros; Mavrouli, Maria; Marka, Andriani; Tserkezou, Persefoni; Baka, Agoritsa; Billinis, Charalambos; Katsioulis, Antonios; Psaroulaki, Anna; Papa, Anna; Papadopoulos, Nikos; Mamuris, Zissis; Tsakris, Athanasios; Kremastinou, Jenny

    2015-01-01

    Cases of West Nile Virus (WNV) disease were recorded for three consecutive years in Greece following the year 2010 outbreak. A cross-sectional serologic survey was conducted to estimate the WNV seroprevalence and assess the ratio of infection to neuroinvasive disease. A stratified left-over sampling methodology was used including age and residence strata. A total of 3,962 serum samples was collected and tested for WNV Immunoglobulin G (IgG) antibodies by Enzyme–Linked Immunosorbent Assay (ELISA). All positive samples were further tested by Plaque Reduction Neutralization Test (PRNT) and WNV Immunoglobulin M (IgM) antibodies. WNV IgG antibodies were detected in 82 samples and 61 were also positive in PRNT representing a weighted seroprevalence of 2.1% (95% C.I.: 1.7–2.6) and 1.5% (95% C.I.: 1.2–2.0), respectively. Multivariable analysis showed that seroprevalence was associated with age and residence. The overall ratio of neuroinvasive disease to infected persons was estimated at 1:376 (95% C.I.: 1:421–1:338), while the elderly people had the highest ratio. This nationwide study provided valuable data regarding the epidemiology of WNV in Greece based on the fact that elderly people have higher risk of being both infected and having severe disease. PMID:26605539

  4. West Nile Virus State of the Art Report of MALWEST Project

    Directory of Open Access Journals (Sweden)

    Andriani Marka

    2013-12-01

    Full Text Available During the last three years Greece is experiencing the emergence of West Nile virus (WNV epidemics. Within this framework, an integrated surveillance and control programme (MALWEST project with thirteen associate partners was launched aiming to investigate the disease and suggest appropriate interventions. One out of seven work packages of the project is dedicated to the State of the Art report for WNV. Three expert working groups on humans, animals and mosquitoes were established. Medical databases (PubMed, Scopus were searched together with websites: e.g., WHO, CDC, ECDC. In total, 1,092 relevant articles were initially identified and 258 of them were finally included as references regarding the current knowledge about WNV, along with 36 additional sources (conference papers, reports, book chapters. The review is divided in three sections according to the fields of interest: (1 WNV in humans (epidemiology, molecular characteristics, transmission, diagnosis, treatment, prevention, surveillance; (2 WNV in animals (epidemiological and transmission characteristics concerning birds, horses, reptiles and other animal species and (3 WNV in mosquitoes (control, surveillance. Finally, some examples of integrated surveillance programmes are presented. The introduction and establishment of the disease in Greece and other European countries further emphasizes the need for thorough research and broadening of our knowledge on this viral pathogen.

  5. Utilizing hunter harvest effort to survey for wildlife disease: a case study of West Nile virus in greater sage-grouse

    Science.gov (United States)

    Dusek, Robert J.; Hagen, Christian A.; Franson, J. Christian; Budeau, David A.; Hofmeister, Erik K.

    2014-01-01

    Greater sage-grouse (Centrocercus urophasianus; sage-grouse) are highly susceptible to infection with West Nile virus (WNV), with substantial mortality reported in wild populations and in experimentally infected birds. Although sage-grouse are hunted throughout much of their range, they have also recently been considered for protection under the Endangered Species Act. We used blood samples collected on filter-paper strips during the 2006–2010 Oregon, USA, annual sage-grouse hunt to survey for specific WNV-neutralizing antibodies that indicate a previous infection with WNV. During this period, hunters submitted 1,880 blood samples from sage-grouse they harvested. Samples obtained were proportional for all 12 Oregon sage-grouse hunting units. Laboratory testing of 1,839 samples by the WNV epitope-blocking enzyme-linked immunosorbent assay (bELISA) followed by plaque reduction neutralization test on bELISA-positive samples yielded 19 (1%) and 1 (0.05%) positive samples, respectively. These data provided early baseline information for future comparisons regarding the prevalence of WNV-specific neutralizing antibodies in sage-grouse in Oregon. This methodology may provide other states where sage-grouse (or other species) populations are hunted and where WNV constitutes a species conservation concern with a viable option to track the relative prevalence of the virus in populations.

  6. Sequencing of sporadic Attention-Deficit Hyperactivity Disorder (ADHD) identifies novel and potentially pathogenic de novo variants and excludes overlap with genes associated with autism spectrum disorder.

    Science.gov (United States)

    Kim, Daniel Seung; Burt, Amber A; Ranchalis, Jane E; Wilmot, Beth; Smith, Joshua D; Patterson, Karynne E; Coe, Bradley P; Li, Yatong K; Bamshad, Michael J; Nikolas, Molly; Eichler, Evan E; Swanson, James M; Nigg, Joel T; Nickerson, Deborah A; Jarvik, Gail P

    2017-06-01

    Attention-Deficit Hyperactivity Disorder (ADHD) has high heritability; however, studies of common variation account for ADHD variance. Using data from affected participants without a family history of ADHD, we sought to identify de novo variants that could account for sporadic ADHD. Considering a total of 128 families, two analyses were conducted in parallel: first, in 11 unaffected parent/affected proband trios (or quads with the addition of an unaffected sibling) we completed exome sequencing. Six de novo missense variants at highly conserved bases were identified and validated from four of the 11 families: the brain-expressed genes TBC1D9, DAGLA, QARS, CSMD2, TRPM2, and WDR83. Separately, in 117 unrelated probands with sporadic ADHD, we sequenced a panel of 26 genes implicated in intellectual disability (ID) and autism spectrum disorder (ASD) to evaluate whether variation in ASD/ID-associated genes were also present in participants with ADHD. Only one putative deleterious variant (Gln600STOP) in CHD1L was identified; this was found in a single proband. Notably, no other nonsense, splice, frameshift, or highly conserved missense variants in the 26 gene panel were identified and validated. These data suggest that de novo variant analysis in families with independently adjudicated sporadic ADHD diagnosis can identify novel genes implicated in ADHD pathogenesis. Moreover, that only one of the 128 cases (0.8%, 11 exome, and 117 MIP sequenced participants) had putative deleterious variants within our data in 26 genes related to ID and ASD suggests significant independence in the genetic pathogenesis of ADHD as compared to ASD and ID phenotypes. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Case series of probable sporadic Creutzfeldt-Jakob disease from Eastern India

    Directory of Open Access Journals (Sweden)

    Atanu Biswas

    2013-01-01

    Full Text Available Background: Creutzfeldt-Jakob disease is a rapidly progressive, fatal, transmissible neurodegenerative disorder caused by prion protein. It is still considered rare in countries like India. This is probably due to nonavailability of autopsy studies in majority of the center. The recent European diagnostic criterion for sporadic CJD (sCJD is useful for making an early diagnosis. Objective: To report a series of patients of probable sCJD from a neurology institute of eastern India. Materials and Methods: Patients of rapidly developing dementia fulfilling the diagnostic criteria for sCJD were included. All were investigated in detail to find out any possible treatable cause including electroencephalography (EEG, magnetic resonance imaging (MRI of brain, and cerebrospinal fluid analysis. Results: A total 10 patients of probable sCJD diagnosed using the European diagnostic criterion between December 2011 and January 2013. The clinical features are consistent with other reported series. While 60% of patients had the classical EEG findings, 100% had typical MRI features. Eight patients died within a mean duration of 4.56 months from the disease onset. Conclusions: The clinical features are similar to other reported series. Our observation raises question about the prevalence of this disease in India which needs more elaborate studies.

  8. Seasonal correlation of sporadic schizophrenia to Ixodes ticks and Lyme borreliosis

    Directory of Open Access Journals (Sweden)

    Fritzsche Markus

    2002-11-01

    Full Text Available Abstract Background Being born in winter and spring is considered one of the most robust epidemiological risk factors for schizophrenia. The aetiology and exact timing of this birth excess, however, has remained elusive so far. Since during phylogeny, Borrelia DNA has led to multiple germ-line mutations within the CB1 candidate gene for schizophrenia, a meta analysis has been performed of all papers on schizophrenic birth excesses with no less than 3000 cases each. All published numerical data were then plotted against the seasonal distributions of Ixodes ticks worldwide. Results In the United States, Europe and Japan the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodes ticks nine months earlier at the time of conception. South of the Wallace Line, which limits the spread of Ixodes ticks and Borrelia burgdorferi into Australia, seasonal trends are less significant, and in Singapore, being non-endemic for Ixodes ticks and Lyme disease, schizophrenic birth excesses are absent. Conclusion At present, it cannot be excluded that prenatal infection by B. burgdorferi is harmful to the implanting human blastocyst. The epidemiological clustering of sporadic schizophrenia by season and locality rather emphasises the risk to the unborn of developing a congenital, yet preventable brain disorder later in life.

  9. Short telomeres: from dyskeratosis congenita to sporadic aplastic anemia and malignancy.

    Science.gov (United States)

    Gramatges, Maria M; Bertuch, Alison A

    2013-12-01

    Telomeres are DNA-protein structures that form a protective cap on chromosome ends. As such, they prevent the natural ends of linear chromosomes from being subjected to DNA repair activities that would result in telomere fusion, degradation, or recombination. Both the DNA and protein components of the telomere are required for this essential function, because insufficient telomeric DNA length, loss of the terminal telomeric DNA structure, or deficiency of key telomere-associated factors may elicit a DNA damage response and result in cellular senescence or apoptosis. In the setting of failed checkpoint mechanisms, such DNA-protein defects can also lead to genomic instability through telomere fusions or recombination. Thus, as shown in both model systems and in humans, defects in telomere biology are implicated in cellular and organismal aging as well as in tumorigenesis. Bone marrow failure and malignancy are 2 life-threatening disease manifestations in the inherited telomere biology disorder dyskeratosis congenita. We provide an overview of basic telomere structure and maintenance. We outline the telomere biology defects observed in dyskeratosis congenita, focusing on recent discoveries in this field. Last, we review the evidence of how telomere biology may impact sporadic aplastic anemia and the risk for various cancers. Copyright © 2013 Mosby, Inc. All rights reserved.

  10. Generation of a human induced pluripotent stem cell line (CSC-42 from a patient with sporadic form of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ekaterina Savchenko

    2018-03-01

    Full Text Available Skin fibroblasts were collected from a 44-year-old patient with sporadic case of Parkinson's disease (PD. The non-integrating Sendai virus vector encoding OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced pluripotent stem cells (iPSCs. Generated iPSCs had normal karyotypes, expressed common stem cell markers, and were capable of differentiating into all three germ layers. Generated line could be used for PD modeling to understand the mechanisms that influence the disorder.

  11. A novel BRCA2 in frame deletion in a Tunisian woman with early onset sporadic breast cancer.

    Science.gov (United States)

    Hadiji-Abbes, N; Trifa, F; Choura, M; Khabir, A; Sellami-Boudawara, T; Frikha, M; Daoud, J; Mokdad-Gargouri, R

    2015-09-01

    Breast cancer is increasing among young women in Tunisia. Germline mutations in the BRCA1/2 genes are associated with a high risk for breast cancer development. However, the true contribution of BRCA1/2 mutation in sporadic breast cancer is not well documented. Our aim is to identify the BRCA2 mutation spectrum in Tunisian young women with breast cancer. Screening the BRCA2 gene was performed using DHPLC, DNA sequencing and PCR-RFLP. We identified, in a woman diagnosed with early onset breast cancer, and without family history, a novel in frame deletion 5456delGTAGCA in the exon 11 of the BRCA2 gene which causes a loss of two residues Ser1743-Ser1744. The absence of this deletion in the patients' parents suggests that it is a de novo variant. Furthermore, we screened 108 sporadic cases, 50 familial cases, and 60 controls for the identified del6bp using PCR-RFLP. None of them carried this deletion suggesting that this variant is not a benign polymorphism and probably rare in our population. With regards to the position of the Ser1743-1744 in the BRCT domain, sequence alignment revealed that the Ser1743 is conserved among several species, which may reflect its importance in the BRCA2 function. A modeling of the wild-type and mutated BRC5-BRC6 domain revealed that the deletion of the 2 Serine residues might affect the structure of this BRCA2 domain. A novel in frame deletion 5456del6bp in BRCA2 gene was identified in an early onset woman with breast cancer and without family history. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Risk factors and analysis of long-term headache in sporadic vestibular schwannoma: a multicenter cross-sectional study.

    Science.gov (United States)

    Carlson, Matthew L; Tveiten, Øystein Vesterli; Driscoll, Colin L; Boes, Christopher J; Sullan, Molly J; Goplen, Frederik K; Lund-Johansen, Morten; Link, Michael J

    2015-11-01

    The primary goals of this study were: 1) to examine the influence of disease and treatment on headache in patients with sporadic vestibular schwannoma (VS); and 2) to identify clinical predictors of long-term headache disability. This was a cross-sectional observational study with international multicenter enrollment. Patients included those with primary sporadic Headache Disability Inventory (HDI), the Hospital Anxiety and Depression Scale, and a VS symptom questionnaire. The main outcome measures were univariate and multivariable associations with HDI total score. The overall survey response rate was 79%. Data from 538 patients with VS were analyzed. The mean age at time of survey was 64 years, 56% of patients were female, and the average duration between treatment and survey was 7.7 years. Twenty-seven percent of patients received microsurgery, 46% stereotactic radiosurgery, and 28% observation. Patients with VS who were managed with observation were more than twice as likely to have severe headache disability compared with 103 control subjects without VS. When accounting for baseline differences, there was no statistically significant difference in HDI outcome between treatment modalities at time of survey. Similarly, among the microsurgery cohort, the long-term risk of severe headache disability was not different between surgical approaches. Multivariable regression demonstrated that younger age, greater anxiety and depression, and a preexisting diagnosis of headache were the primary predictors of severe long-term headache disability, while tumor size and treatment modality had little influence. At a mean of almost 8 years following treatment, approximately half of patients with VS experience headaches of varying frequency and severity. Patient-driven factors including age, sex, mental health, and preexisting headache syndrome are the strongest predictors of long-term severe headache disability. Tumor size and treatment modality have less impact. These data

  13. The impact of West Nile virus on the abundance of selected North American birds

    Directory of Open Access Journals (Sweden)

    Beard Raphaelle H

    2011-08-01

    Full Text Available Abstract Background The emergence of West Nile virus (WNV in North America has been associated with high mortality in the native avifauna and has raised concerns about the long-term impact of WNV on bird populations. Here, we present results from a longitudinal analysis of annual counts of six bird species, using North American Breeding Bird Survey data from ten states (1994 to 2010. We fit overdispersed Poisson models to annual counts. Counts from successive years were linked by an autoregressive process that depended on WNV transmission intensity (annual West Nile neuroinvasive disease reports and was adjusted by El Niño Southern Oscillation events. These models were fit using a Markov chain Monte Carlo algorithm. Results Model fit was mostly excellent, especially for American Crows, for which our models explained between 26% and 81% of the observed variance. The impact of WNV on bird populations was quantitatively evaluated by contrasting hypothetical count trajectories (omission of WNV with observed counts. Populations of American crows were most consistently affected with a substantial cumulative impact in six of ten states. The largest negative impact, almost 60%, was found in Illinois. A regionally substantial decline was also seen for American Robins and House Sparrows, while the other species appeared unaffected. Conclusions Our results confirm findings from previous studies that single out American Crows as the species most vulnerable to WNV infection. We discuss strengths and limitations of this and other methods for quantifying the impact of WNV on bird populations.

  14. Monitoring of West Nile virus, Usutu virus and Meaban virus in waterfowl used as decoys and wild raptors in southern Spain.

    Science.gov (United States)

    Jurado-Tarifa, E; Napp, S; Lecollinet, S; Arenas, A; Beck, C; Cerdà-Cuéllar, M; Fernández-Morente, M; García-Bocanegra, I

    2016-12-01

    In the last decade, the number of emerging flaviviruses described worldwide has increased considerably, with wild birds acting as the main reservoir hosts of these viruses. We carried out an epidemiological survey to determine the seroprevalence of antigenically related flaviviruses, particularly West Nile virus (WNV), Usutu virus (USUV) and Meaban virus (MBV), in waterfowl used as decoys and wild raptors in Andalusia (southern Spain), the region considered to have the highest risk of flaviviruses circulation in Spain. The overall flaviviruses seroprevalence according to bELISA was 13.0% in both in decoys (n=1052) and wild raptors (n=123). Specific antibodies against WNV, USUV and MBV were confirmed by micro virus neutralization tests in 12, 38 and 4 of the seropositive decoys, respectively. This is the first study on WNV and USUV infections in decoys and the first report of MBV infections in waterfowl and raptors. Moreover we report the first description of WNV infections in short-toed snake eagle (Circaetus gallicus) and Montagu's harrier (Circus pygargus). The seropositivity obtained indicates widespread but not homogeneous distribution of WNV and USUV in Andalusia. The results also confirm endemic circulation of WNV, USUV and MBV in both decoys and wild raptors in southern Spain. Our results highlight the need to implement surveillance and control programs not only for WNV but also for other related flaviviruses. Further research is needed to determine the eco-epidemiological role that waterfowl and wild raptors play in the transmission of emerging flaviviruses, especially in decoys, given their close interactions with humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Phrenic nerve deficits and neurological immunopathology associated with acute West Nile virus infection in mice and hamsters.

    Science.gov (United States)

    Zukor, Katherine; Wang, Hong; Hurst, Brett L; Siddharthan, Venkatraman; Van Wettere, Arnaud; Pilowsky, Paul M; Morrey, John D

    2017-04-01

    Neurological respiratory deficits are serious outcomes of West Nile virus (WNV) disease. WNV patients requiring intubation have a poor prognosis. We previously reported that WNV-infected rodents also appear to have respiratory deficits when assessed by whole-body plethysmography and diaphragmatic electromyography. The purpose of this study was to determine if the nature of the respiratory deficits in WNV-infected rodents is neurological and if deficits are due to a disorder of brainstem respiratory centers, cervical spinal cord (CSC) phrenic motor neuron (PMN) circuitry, or both. We recorded phrenic nerve (PN) activity and found that in WNV-infected mice, PN amplitude is reduced, corroborating a neurological basis for respiratory deficits. These results were associated with a reduction in CSC motor neuron number. We found no dramatic deficits, however, in brainstem-mediated breathing rhythm generation or responses to hypercapnia. PN frequency and pattern parameters were normal, and all PN parameters changed appropriately upon a CO 2 challenge. Histological analysis revealed generalized microglia activation, astrocyte reactivity, T cell and neutrophil infiltration, and mild histopathologic lesions in both the brainstem and CSC, but none of these were tightly correlated with PN function. Similar results in PN activity, brainstem function, motor neuron number, and histopathology were seen in WNV-infected hamsters, except that histopathologic lesions were more severe. Taken together, the results suggest that respiratory deficits in acute WNV infection are primarily due to a lower motor neuron disorder affecting PMNs and the PN rather than a brainstem disorder. Future efforts should focus on markers of neuronal dysfunction, axonal degeneration, and myelination.

  16. Differential motor neuron impairment and axonal regeneration in sporadic and familiar amyotrophic lateral sclerosis with SOD-1 mutations: lessons from neurophysiology.

    Science.gov (United States)

    Bocci, Tommaso; Pecori, Chiara; Giorli, Elisa; Briscese, Lucia; Tognazzi, Silvia; Caleo, Matteo; Sartucci, Ferdinando

    2011-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O(-2)) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS patients (34 males; 26 females) were enrolled in the study and examined basally (T0) and every 4 months (T1, T2, and T3). Fifteen of these patients are SOD-1 symptomatic mutation carriers (nine males, six females). We used Macro-EMG and Motor Unit Number Estimation (MUNE) in order to evaluate the neuronal loss and the re-innervation process at the onset of disease and during follow-up period. SOD-1 mutation carriers have a higher number of motor units at the moment of diagnosis when compared with the sporadic form, despite a more dramatic drop in later stages. Moreover, in familiar SOD-1 ALS there is not a specific time interval in which the axonal regeneration can balance the neuronal damage. Taken together, these results strengthen the idea of a different pathogenetic mechanism at the base of sALS and fALS.

  17. Differential Motor Neuron Impairment and Axonal Regeneration in Sporadic and Familiar Amyotrophic Lateral Sclerosis with SOD-1 Mutations: Lessons from Neurophysiology

    Directory of Open Access Journals (Sweden)

    Tommaso Bocci

    2011-12-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1 gene. SOD-1 catalyses the superoxide radical (O−2 into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS patients (34 males; 26 females were enrolled in the study and examined basally (T0 and every 4 months (T1, T2, and T3. Fifteen of these patients are SOD-1 symptomatic mutation carriers (nine males, six females. We used Macro-EMG and Motor Unit Number Estimation (MUNE in order to evaluate the neuronal loss and the re-innervation process at the onset of disease and during follow-up period. Results and Discussion: SOD-1 mutation carriers have a higher number of motor units at the moment of diagnosis when compared with the sporadic form, despite a more dramatic drop in later stages. Moreover, in familiar SOD-1 ALS there is not a specific time interval in which the axonal regeneration can balance the neuronal damage. Taken together, these results strengthen the idea of a different pathogenetic mechanism at the base of sALS and fALS.

  18. Increased androgen, anti-Müllerian hormone, and sporadic anovulation in healthy, eumenorrheic women: a mild PCOS-like phenotype?

    Science.gov (United States)

    Sjaarda, Lindsey A; Mumford, Sunni L; Kissell, Kerri; Schliep, Karen C; Hammoud, Ahmad O; Perkins, Neil J; Weck, Jennifer; Wactawski-Wende, Jean; Schisterman, Enrique F

    2014-06-01

    Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS) in women with irregular menses, yet the relationship between androgens and ovarian dysfunction remains poorly understood in eumenorrheic women. The objective of the study was to evaluate whether sporadic anovulation was associated with higher T and anti-müllerian hormone (AMH; marker of ovarian follicle count) concentrations in eumenorrheic women. This was a prospective cohort study from 2005 to 2007. The study was conducted at the University of Buffalo in western New York state. A total of 259 eumenorrheic women without a self-reported history of infertility, PCOS, or other endocrine disorder participated in the study. Total T and AMH were measured five to eight times per cycle for one (n = 9) or two (n = 250) cycles per woman (n = 509 cycles) with timing of menstrual cycle phase assisted by fertility monitors. Anovulatory cycles were defined biochemically by progesterone and LH concentrations. Repeated-measures ANOVA was conducted on log-transformed data with adjustment for age. Compared with ovulatory cycles (n = 467), sporadic anovulatory cycles (n = 42) had marginally higher total and significantly higher free T [mean 23.7 ng/dL (95% confidence interval [CI] 21.4-26.3) vs 21.6 ng/dL (95% CI 20.9-22.3), P = .08, and 0.36 ng/dL (95% CI 0.33-0.40) vs 0.32 ng/dL (95% CI 0.31-0.33), P = .02, respectively] during menses and also throughout the luteal phase (P PCOS in women with menstrual disturbances may occur across a continuum of T concentrations, including in eumenorrheic women without clinical hyperandrogenism.

  19. Mortality and Causes of Death in Patients with Sporadic Inclusion Body Myositis: Survey Study Based on the Clinical Experience of Specialists in Australia, Europe and the USA

    NARCIS (Netherlands)

    Price, Mark A.; Barghout, Victoria; Benveniste, Olivier; Christopher-Stine, Lisa; Corbett, Alastair; de Visser, Marianne; Hilton-Jones, David; Kissel, John T.; Lloyd, Thomas E.; Lundberg, Ingrid E.; Mastaglia, Francis; Mozaffar, Tahseen; Needham, Merrilee; Schmidt, Jens; Sivakumar, Kumaraswamy; DeMuro, Carla; Tseng, Brian S.

    2016-01-01

    There is a paucity of data on mortality and causes of death (CoDs) in patients with sporadic inclusion body myositis (sIBM), a rare, progressive, degenerative, inflammatory myopathy that typically affects those aged over 50 years. Based on patient records and expertise of clinical specialists, this

  20. Laboratory Transmission of Japanese Encephalitis and West Nile Viruses by Molestus Form of Culex pipiens (Diptera: Culicidae) Collected in Uzbekistan in 2004

    National Research Council Canada - National Science Library

    Turell, M. J; Mores, C. N; Dohm, D. J; Komilov, N; Paragas, J; Lee, J. S; Shermuhemedova, D; Endy, T. P; Kodirov, A; Khodjaev, S

    2006-01-01

    ... (family Flaviviridae, genus Flavivirus, WNV) viruses under laboratory conditions. These molestus were highly competent laboratory vectors of WNV, with infection and dissemination rates of 96 and 81%, respectively. Approximately 75...

  1. Equatorial E Region Electric Fields and Sporadic E Layer Responses to the Recovery Phase of the November 2004 Geomagnetic Storm

    Science.gov (United States)

    Moro, J.; Resende, L. C. A.; Denardini, C. M.; Xu, J.; Batista, I. S.; Andrioli, V. F.; Carrasco, A. J.; Batista, P. P.; Schuch, N. J.

    2017-12-01

    Equatorial E region electric fields (EEFs) inferred from coherent radar data, sporadic-E (Es) layers observed from a digital ionosonde data, and modeling results are used to study the responses of the equatorial E region over São Luís (SLZ, 2.3°S, 44.2°W, -7° dip angle), Brazil, during the super storm of November 2004. The EEF is presented in terms of the zonal (Ey) and vertical (Ez) components in order to analyze the corresponding characteristics of different types of Es seen in ionograms and simulated with the E region ionospheric model. We bring out the variabilities of Ey and Ez components with storm time changes in the equatorial E region. In addition, some aspects of the electric fields and Es behavior in three cases of weak, very weak, and strong Type II occurrences during the recovery phase of the geomagnetic storm are discussed. The connection between the enhanced occurrence and suppressions of the Type II irregularities and the q-type Es (Esq) controlled by electric fields, with the development or disruption of the blanketing sporadic E (Esb) layers produced by wind shear mechanism, is also presented. The mutual presence of Esq along with the Esb occurrences is a clear indicator of the secular drift of the magnetic equator and hence that of the equatorial electrojet (EEJ) over SLZ. The results show evidence about the EEJ and Es layer electrodynamics and coupling during geomagnetic disturbance time electric fields.

  2. Recent progress in West Nile virus diagnosis and vaccination

    Directory of Open Access Journals (Sweden)

    De Filette Marina

    2012-03-01

    Full Text Available Abstract West Nile virus (WNV is a positive-stranded RNA virus belonging to the Flaviviridae family, a large family with 3 main genera (flavivirus, hepacivirus and pestivirus. Among these viruses, there are several globally relevant human pathogens including the mosquito-borne dengue virus (DENV, yellow fever virus (YFV, Japanese encephalitis virus (JEV and West Nile virus (WNV, as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV. Since the mid-1990s, outbreaks of WN fever and encephalitis have occurred throughout the world and WNV is now endemic in Africa, Asia, Australia, the Middle East, Europe and the Unites States. This review describes the molecular virology, epidemiology, pathogenesis, and highlights recent progress regarding diagnosis and vaccination against WNV infections.

  3. Clinical Manifestations and Outcomes of West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    James J. Sejvar

    2014-02-01

    Full Text Available Since the emergence of West Nile virus (WNV in North America in 1999, understanding of the clinical features, spectrum of illness and eventual functional outcomes of human illness has increased tremendously. Most human infections with WNV remain clinically silent. Among those persons developing symptomatic illness, most develop a self-limited febrile illness. More severe illness with WNV (West Nile neuroinvasive disease, WNND is manifested as meningitis, encephalitis or an acute anterior (polio myelitis. These manifestations are generally more prevalent in older persons or those with immunosuppression. In the future, a more thorough understanding of the long-term physical, cognitive and functional outcomes of persons recovering from WNV illness will be important in understanding the overall illness burden.

  4. Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases.

    Science.gov (United States)

    Nishino, Koichi; Yoshimi, Kaku; Shibuya, Tomoyoshi; Hayashi, Takuo; Mitani, Keiko; Kobayashi, Etsuko; Ichikawa, Masako; Asao, Tetsuhiko; Suzuki, Yohei; Sato, Tadashi; Shiota, Satomi; Kodama, Yuzo; Takahashi, Kazuhisa; Seyama, Kuniaki

    2017-01-01

    This report describes two patients with sporadic lymphangioleiomyomatosis complicated by protein-losing enteropathy (PLE). Imaging studies indicated retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one patient; whereas the site in the other patient was intestinal. Treatment with sirolimus led to the complete resolution of PLE within several months; additionally, marked shrinkage was observed in the lymphangioleiomyomas of both cases. These findings suggest that colonic or intestinal lymphatic congestion due to neighboring lymphangioleiomyomas was the mechanism for the development of PLE. At the time of writing this report, the beneficial effect of sirolimus has lasted for more than 3 years.

  5. Differential Motor Neuron Impairment and Axonal Regeneration in Sporadic and Familiar Amyotrophic Lateral Sclerosis with SOD-1 Mutations: Lessons from Neurophysiology

    OpenAIRE

    Bocci, Tommaso; Pecori, Chiara; Giorli, Elisa; Briscese, Lucia; Tognazzi, Silvia; Caleo, Matteo; Sartucci, Ferdinando

    2011-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O−2) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS pa...

  6. LGI1 antibody encephalopathy overlapping with sporadic Creutzfeldt-Jakob disease

    Science.gov (United States)

    Kim, Boaz; Yoo, Patrick; Sutherland, Tom; Boyd, Alison; Stehmann, Christiane; McLean, Catriona

    2016-01-01

    Objective: To report a rare case of leucine-rich, glioma inactivated 1 (LGI1) antibody–mediated autoimmune encephalopathy clinically overlapping with pathologically confirmed sporadic Creutzfeldt-Jakob disease (CJD). Methods: The patient was investigated with repeated brain MRI, EEG, CSF examination, whole-body fluorodeoxy-glucose positron emission tomography, genetic analysis of the prion protein gene (PRNP), and extensive serologic screening for paraneoplastic and autoimmune encephalopathy markers. Written informed consent was obtained from the patient's next of kin for access to clinical files for research purposes and for publication. Results: The patient was a 77-year-old man who presented with faciobrachial dystonic seizures (FBDS) secondary to LGI1 antibody–mediated autoimmune encephalopathy, with suggestive MRI findings and a complete response to treatment with combinatorial immunosuppression. Stereotactic biopsy of a nonenhancing T1 hyperintense basal ganglia lesion during the initial FBDS phase, albeit following immunosuppression, did not disclose evidence of lymphocytic inflammation. Following full remission of the FBDS, the patient manifested a rapidly progressive dementia associated with gross motor decline confirmed to be CJD at autopsy (molecular subtype VV3), with no evidence of a pathogenic PRNP mutation. Conclusions: Our patient highlights that these rare diseases are not invariably mutually exclusive and underscores the benefits of comprehensive neuropathologic examination of the brain to achieve an accurate diagnosis, especially in complex cases when the clinical trajectory dramatically deviates and a concomitant disease may need to be conscientiously considered to best explain the new clinical course. PMID:27354985

  7. On the influence of solar activity on the mid-latitude sporadic E layer

    Science.gov (United States)

    Pezzopane, Michael; Pignalberi, Alessio; Pietrella, Marco

    2015-09-01

    To investigate the influence of solar cycle variability on the sporadic E layer (Es), hourly measurements of the critical frequency of the Es ordinary mode of propagation, foEs, and of the blanketing frequency of the Es layer, fbEs, recorded from January 1976 to December 2009 at the Rome (Italy) ionospheric station (41.8° N, 12.5° E), were examined. The results are: (1) a high positive correlation between the F10.7 solar index and foEs as well as between F10.7 and fbEs, both for the whole data set and for each solar cycle separately, the correlation between F10.7 and fbEs being much higher than the one between F10.7 and foEs; (2) a decreasing long-term trend of the F10.7, foEs and fbEs time series, with foEs decreasing more rapidly than F10.7 and fbEs; (3) clear and statistically significant peaks at 11 years in the foEs and fbEs time series, inferred from Lomb-Scargle periodograms.

  8. Energetics and structure of the lower E region associated with sporadic E layer

    Directory of Open Access Journals (Sweden)

    K.-I. Oyama

    2008-09-01

    Full Text Available The electron temperature (Te, electron density (Ne, and two components of the electric field were measured from the height of 90 km to 150 km by one of the sounding rockets launched during the SEEK-2 campaign. The rocket went through sporadic E layer (Es at the height of 102 km–109 km during ascent and 99 km–108 km during decent, respectively. The energy density of thermal electrons calculated from Ne and Te shows the broad maximum in the height range of 100–110 km, and it decreases towards the lower and higher altitudes, which implies that a heat source exists in the height region of 100 km–110 km. A 3-D picture of Es, that was drawn by using Te, Ne, and the electric field data, corresponded to the computer simulation; the main structure of Es is projected to a higher altitude along the magnetic line of force, thus producing irregular structures of Te, Ne and electric field in higher altitude.

  9. Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.

    Directory of Open Access Journals (Sweden)

    Frank P Diekstra

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls. These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls. Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 × 10(-51 withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible

  10. Multiple sporadic colorectal cancers display a unique methylation phenotype.

    Directory of Open Access Journals (Sweden)

    Victoria Gonzalo

    Full Text Available Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC. Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP; KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1. Methylight assays validated the results for 4 selected genes (p = 0.0002. Eight out of 12(66.6% multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2% solitary tumors (p = 0.004. Interestingly, 76 out of the 102 (74.5% hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity.

  11. Spatial variation in host feeding patterns of Culex tarsalis and the Culex pipiens complex (Diptera: Culicidae) in California.

    Science.gov (United States)

    Thiemann, T C; Lemenager, D A; Kluh, S; Carroll, B D; Lothrop, H D; Reisen, W K

    2012-07-01

    West Nile virus (family Flaviviridae, genus Flavivirus, WNV) is now endemic in California across a variety of ecological regions that support a wide diversity of potential avian and mammalian host species. Because different avian hosts have varying competence for WNV, determining the blood-feeding patterns of Culex (Diptera: Culicidae) vectors is a key component in understanding the maintenance and amplification of the virus as well as tangential transmission to humans and horses. We investigated the blood-feeding patterns of Culex tarsalis Coquillett and members of the Culex pipiens L. complex from southern to northern California. Nearly 100 different host species were identified from 1,487 bloodmeals, by using the mitochondrial gene cytochrome c oxidase I (COI). Cx. tarsalis fed on a higher diversity of hosts and more frequently on nonhuman mammals than did the Cx. pipiens complex. Several WNV-competent host species, including house finch and house sparrow, were common bloodmeal sources for both vector species across several biomes and could account for WNV maintenance and amplification in these areas. Highly competent American crow, western scrub-jay and yellow-billed magpie also were fed upon often when available and are likely important as amplifying hosts for WNV in some areas. Neither species fed frequently on humans (Cx. pipiens complex [0.4%], Cx. tarsalis [0.2%]), but with high abundance, both species could serve as both enzootic and bridge vectors for WNV.

  12. The costs of infection and resistance as determinants of West Nile virus susceptibility in Culex mosquitoes

    Directory of Open Access Journals (Sweden)

    Styer Linda M

    2011-10-01

    Full Text Available Abstract Background Understanding the phenotypic consequences of interactions between arthropod-borne viruses (arboviruses and their mosquito hosts has direct implications for predicting the evolution of these relationships and the potential for changes in epidemiological patterns. Although arboviruses are generally not highly pathogenic to mosquitoes, pathology has at times been noted. Here, in order to evaluate the potential costs of West Nile virus (WNV infection and resistance in a primary WNV vector, and to assess the extent to which virus-vector relationships are species-specific, we performed fitness studies with and without WNV exposure using a highly susceptible Culex pipiens mosquito colony. Specifically, we measured and compared survival, fecundity, and feeding rates in bloodfed mosquitoes that were (i infected following WNV exposure (susceptible, (ii uninfected following WNV exposure (resistant, or (iii unexposed. Results In contrast to our previous findings with a relatively resistant Cx. tarsalis colony, WNV infection did not alter fecundity or blood-feeding behaviour of Cx. pipiens, yet results do indicate that resistance to infection is associated with a fitness cost in terms of mosquito survival. Conclusions The identification of species-specific differences provides an evolutionary explanation for variability in vector susceptibility to arboviruses and suggests that understanding the costs of infection and resistance are important factors in determining the potential competence of vector populations for arboviruses.

  13. Naturally induced humoral immunity to West Nile virus infection in raptors.

    Science.gov (United States)

    Nemeth, Nicole M; Kratz, Gail E; Bates, Rebecca; Scherpelz, Judy A; Bowen, Richard A; Komar, Nicholas

    2008-09-01

    West Nile virus (WNV) infection can be fatal to many bird species, including numerous raptors, though population- and ecosystem-level impacts following introduction of the virus to North America have been difficult to document. Raptors occupy a diverse array of habitats worldwide and are important to ecosystems for their role as opportunistic predators. We documented initial (primary) WNV infection and then regularly measured WNV-specific neutralizing antibody titers in 16 resident raptors of seven species, plus one turkey vulture. Most individuals were initially infected and seroconverted between July and September of 2003, though three birds remained seronegative until summer 2006. Many of these birds became clinically ill upon primary infection, with clinical signs ranging from loss of appetite to moderate neurological disease. Naturally induced WNV neutralizing antibody titers remained essentially unchanged in some birds, while eight individuals experienced secondary rises in titer presumably due to additional exposures at 1, 2, or 3 years following primary infection. No birds experienced clinical signs surrounding or following the time of secondary exposure, and therefore antibodies were considered protective. Results of this study have implications for transmission dynamics of WNV and health of raptor populations, as well as the interpretation of serologic data from free-ranging and captive birds. Antibodies in raptors surviving WNV may persist for multiple years and protect against potential adverse effects of subsequent exposures.

  14. ROLE OF DNA METHYLATION AS A DIAGNOSTIC BIOMARKER OF SPORADIC BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Wirsma Arif Harahap

    2017-02-01

    Full Text Available The initiation and progression of breast cancer have been recognized for many years to be secondary to the accumulation of genetic mutations which lead to aberrant cellular function. Genetic mutations, either inherited or sporadic, may result in the activation of oncogenes and the inactivation of tumor suppressor genes. The more recent discovery that reversible alterations in histone proteins and deoxyribonucleic acid (DNA can also lead to tumorigenesis has introduced a novel term to the field of cancer research: epigenetics.  Epigenetics refers to the study of heritable changes in gene regulation that do not involve a change in the DNA sequence. The most often studied in epigenetics of breast cancer is DNA methylation. That a promoter methylation result in transcription blockade supports the notion that cellular inhibition takes place. Compared to normal tissues, hypermethylation occurs from double to triple in cancerous ones. DNA methylation plays a crucial role in oncogenesis and is one of the hallmarks of cancer. Detection of aberrantly methylated CpG islands in promoter region of several genes in DNA sample derived from nipple aspirates, serum, or cancer tissue associated with down regulation of expression or loss of function of these genes has been associated with early stages of breast cancer, where  hypermethylation of CpG island points to poorer prognosis in breast cancer.  DNA methylation has been identified as signature for TNBC. Methylation of BRCA1 gene is frequently demonstrated in young, estrogen receptor-negative breast cancer patients. Methylation of specific genes is known to differ across race and socioeconomic status. BRCA1 methylation in premenopausal women with sporadic breast cancer in West Sumatra region has been higher than in Western women. DNA methylation may be used to enhance current breast cancer classification. There is such a distinction between methylation and gene expression profiles of breast cancer that not

  15. Genomic Alterations Observed in Colitis-Associated Cancers Are Distinct From Those Found in Sporadic Colorectal Cancers and Vary by Type of Inflammatory Bowel Disease.

    Science.gov (United States)

    Yaeger, Rona; Shah, Manish A; Miller, Vincent A; Kelsen, Judith R; Wang, Kai; Heins, Zachary J; Ross, Jeffrey S; He, Yuting; Sanford, Eric; Yantiss, Rhonda K; Balasubramanian, Sohail; Stephens, Philip J; Schultz, Nikolaus; Oren, Moshe; Tang, Laura; Kelsen, David

    2016-08-01

    Patients with inflammatory bowel diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), are at increased risk for small bowel or colorectal cancers (colitis-associated cancers [CACs]). We compared the spectrum of genomic alterations in CACs with those of sporadic colorectal cancers (CRCs) and investigated differences between CACs from patients with CD vs UC. We studied tumor tissues from patients with CACs treated at Memorial Sloan Kettering Cancer Center or Weill Cornell Medical College from 2003 through 2015. We performed hybrid capture-based next-generation sequencing analysis of >300 cancer-related genes to comprehensively characterize genomic alterations. We performed genomic analyses of 47 CACs (from 29 patients with UC and 18 with CD; 43 primary tumors and 4 metastases). Primary tumors developed in the ileum (n = 2), right colon (n = 18), left colon (n = 6), and rectosigmoid or rectum (n = 21). We found genomic alterations in TP53, IDH1, and MYC to be significantly more frequent, and mutations in APC to be significantly less frequent, than those reported in sporadic CRCs by The Cancer Genome Atlas or Foundation Medicine. We identified genomic alterations that might be targeted by a therapeutic agent in 17 of 47 (36%) CACs. These included the mutation encoding IDH1 R132; amplification of FGFR1, FGFR2, and ERBB2; and mutations encoding BRAF V600E and an EML4-ALK fusion protein. Alterations in IDH1 and APC were significantly more common in CACs from patients with CD than UC. In an analysis of CACs from 47 patients, we found significant differences in the spectrum of genomic alterations in CACs compared with sporadic CRCs. We observed a high frequency of IDH1 R132 mutations in patients with CD but not UC, as well as a high frequency of MYC amplification in CACs. Many genetic alterations observed in CACs could serve as therapeutic targets. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. A Serological Protein Microarray for Detection of Multiple Cross-Reactive Flavivirus Infections in Horses for Veterinary and Public Health Surveillance.

    Science.gov (United States)

    Cleton, N B; van Maanen, K; Bergervoet, S A; Bon, N; Beck, C; Godeke, G-J; Lecollinet, S; Bowen, R; Lelli, D; Nowotny, N; Koopmans, M P G; Reusken, C B E M

    2017-12-01

    The genus Flavivirus in the family Flaviviridae includes some of the most important examples of emerging zoonotic arboviruses that are rapidly spreading across the globe. Japanese encephalitis virus (JEV), West Nile virus (WNV), St. Louis encephalitis virus (SLEV) and Usutu virus (USUV) are mosquito-borne members of the JEV serological group. Although most infections in humans are asymptomatic or present with mild flu-like symptoms, clinical manifestations of JEV, WNV, SLEV, USUV and tick-borne encephalitis virus (TBEV) can include severe neurological disease and death. In horses, infection with WNV and JEV can lead to severe neurological disease and death, while USUV, SLEV and TBEV infections are mainly asymptomatic, however, and induce antibody responses. Horses often serve as sentinels to monitor active virus circulation in serological surveillance programmes specifically for WNV, USUV and JEV. Here, we developed and validated a NS1-antigen protein microarray for the serological differential diagnosis of flavivirus infections in horses using sera of experimentally and naturally infected symptomatic as well as asymptomatic horses. Using samples from experimentally infected horses, an IgG and IgM specificity of 100% and a sensitivity of 95% for WNV and 100% for JEV was achieved with a cut-off titre of 1 : 20 based on ROC calculation. In field settings, the microarray identified 93-100% of IgG-positive horses with recent WNV infections and 87% of TBEV IgG-positive horses. WNV IgM sensitivity was 80%. Differentiation between closely related flaviviruses by the NS1-antigen protein microarray is possible, even though we identified some instances of cross-reactivity among antibodies. However, the assay is not able to differentiate between naturally infected horses and animals vaccinated with an inactivated WNV whole-virus vaccine. We showed that the NS1-microarray can potentially be used for diagnosing and distinguishing flavivirus infections in horses and for public

  17. Neutralizing activities of human immunoglobulin derived from donors in Japan against mosquito-borne flaviviruses, Japanese encephalitis virus, West Nile virus, and dengue virus

    Directory of Open Access Journals (Sweden)

    Yunoki M

    2016-07-01

    Full Text Available Mikihiro Yunoki,1-3 Takeshi Kurosu,2 Ritsuko Kubota Koketsu,2,4 Kazuo Takahashi,5 Yoshinobu Okuno,4 Kazuyoshi Ikuta2,4 1Research and Development Division, Japan Blood Products Organization, Tokyo, 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 3Pathogenic Risk Evaluation, Graduate School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, 4Research and Development Division, The Research Foundation for Microbial Diseases of Osaka University, Kagawa, 5Osaka Prefectural Institute of Public Health, Osaka, Japan Abstract: Japanese encephalitis virus (JEV, West Nile virus (WNV, and dengue virus (DenV are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. Keywords

  18. Synergized resmethrin and corticosterone alter the chicken's response to west nile virus

    Energy Technology Data Exchange (ETDEWEB)

    Jankowski, Mark David [Los Alamos National Laboratory; Franson, J Christian [US GEOLOGICAL SURVEY; Mostl, Erich [UNIV OF VIENNA; Porter, Warren P [UNIV OF WISCONSIN; Hofmeister, Erik K [US GEOLOGICAL SURVEY

    2009-01-01

    Debate concerning arbovirus control strategies remains contentious because concern regarding the relative risk of viral infection and environmental toxicant exposure is high but inadequately characterized. Taking this into account, mosquito control agencies employ aerial insecticides only after arbovirus surveillance data indicate high local mosquito-infection-rates. Successfully mitigating the risk of adult-mosquito-control insecticides ('adulticides') to non-target species such as humans, domestic animals, fish, beneficial insects and wildlife, while increasing their efficacy to reduce arbovirus outbreak intensity requires targeted scientific data from animal toxicity studies and environmental monitoring activities. Wild birds are an important reservoir host for WNv and are potentially exposed to insecticides used for mosquito control. However, no risk assessments have evaluated whether insecticides augment or extend the potential transmissibility of West Nile virus (WNv) in birds. In order to augment existing resmethrin risk assessments, we aimed to determine whether synergized resmethrin (SR) may cause chickens to develop an elevated or extended WN viremia and if subacute stress may affect its immunotoxicity. We distributed 40 chickens into four groups then exposed them prior to and during WNv infection with SR (50 {mu}g/l resmethrin + 150 {mu}g/l piperonyl butoxide) and/or 20 mg/I corticosterone (CORT) in their drinking-water. Corticosterone was given for 10 continuous days and SR was given for 3 alternate days starting the 3rd day of CORT exposure, then chickens were subcutaneously inoculated with WNv on the 5th day of CORT treatment. Compared to controls, CORT treatment extended and elevated viremia, enhanced WNv-specific antibody and increased the percentage of birds that shed oral virus, whereas SR treatment extended viremia, depressed WNv-specific IgG, and increased the percentage of CORT-treated birds that shed oral virus. Corticosterone and SR

  19. Spatio-temporal patterns of distribution of West Nile virus vectors in eastern Piedmont Region, Italy

    Directory of Open Access Journals (Sweden)

    Bisanzio Donal

    2011-12-01

    Full Text Available Abstract Background West Nile Virus (WNV transmission in Italy was first reported in 1998 as an equine outbreak near the swamps of Padule di Fucecchio, Tuscany. No other cases were identified during the following decade until 2008, when horse and human outbreaks were reported in Emilia Romagna, North Italy. Since then, WNV outbreaks have occurred annually, spreading from their initial northern foci throughout the country. Following the outbreak in 1998 the Italian public health authority defined a surveillance plan to detect WNV circulation in birds, horses and mosquitoes. By applying spatial statistical analysis (spatial point pattern analysis and models (Bayesian GLMM models to a longitudinal dataset on the abundance of the three putative WNV vectors [Ochlerotatus caspius (Pallas 1771, Culex pipiens (Linnaeus 1758 and Culex modestus (Ficalbi 1890] in eastern Piedmont, we quantified their abundance and distribution in space and time and generated prediction maps outlining the areas with the highest vector productivity and potential for WNV introduction and amplification. Results The highest abundance and significant spatial clusters of Oc. caspius and Cx. modestus were in proximity to rice fields, and for Cx. pipiens, in proximity to highly populated urban areas. The GLMM model showed the importance of weather conditions and environmental factors in predicting mosquito abundance. Distance from the preferential breeding sites and elevation were negatively associated with the number of collected mosquitoes. The Normalized Difference Vegetation Index (NDVI was positively correlated with mosquito abundance in rice fields (Oc. caspius and Cx. modestus. Based on the best models, we developed prediction maps for the year 2010 outlining the areas where high abundance of vectors could favour the introduction and amplification of WNV. Conclusions Our findings provide useful information for surveillance activities aiming to identify locations where the

  20. SEEK-2 (Sporadic-E Experiment over Kyushu 2 − Project Outline, and Significance

    Directory of Open Access Journals (Sweden)

    R. Pfaff

    2005-10-01

    Full Text Available SEEK-2 (Sporadic-E Experiment over Kyushu 2 is an observation campaign to study the spatial structure of the field-aligned irregularity (FAI and sporadic-E(Es-layer by means of two sounding rockets and a ground-based observation network with radars and optical instruments. The experiment was successfully conducted on 3 August 2002, with successive launches of two sounding rockets from the Uchinoura Space Center (USC of the Japan Aerospace Exploration Agency (JAXA. The timing of the experiment was carefully selected, while intense quasi-periodic (QP echoes were observed with two radars in Tanegashima. The main Es-layer, with its double-layered structure, was observed at altitudes of 103–105 km, the presence of which was well accounted for by the ion accumulation due to neutral-wind shear. Several minor peaks were detected in the electron density profiles at altitudes of up to 130 km. The intensity of the electric field was 5–10 mV/m and showed intense fluctuations below 110 km. Wave-like variation of the electric field was seen above 110 km. From radar experiments, we found that QP echoes appeared around 105 km, which agreed well with the main Es-layer height. The QP echoes propagated to the west-northwest, with frontal structures elongated from north-northeast to south-southwest. Radar observations conduced throughout the SEEK-2 period, on the other hand, showed that frontal structures of the QP echoes were most frequently propagated to the southeast. This result was consistent with the direction of gravity-wave propagation observed with the OH imager during the same period. The rocket beacon experiment with the Es-layers revealed the spatial structure of the plasma densities. On the basis of these results and those from SEEK-1 in 1996, we examined the structures of the nighttime mid-latitude E-region. We concluded that the QP echoes reflect the horizontal structures of the main Es-layers. The source of the structures was not clearly