bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Value of Animal-Side Antibody Assays for Rapid Detection of Mycobacterium bovis or Mycobacterium microti Infection in South American Camelids
Authors: Lyashchenko Konstantin P. , Greenwald Rena , Esfandiari Javan , Rhodes Shelley , Dean Gillian , de la Rua-Domenech Ricardo , Meylan Mireille , Vordermeier HMartin , Zanolari Patrik 
Published: October 2011

ABSTRACTTuberculosis (TB) in South American camelids (SAC) is caused byMycobacterium bovisorMycobacterium microti. Two serological methods, rapid testing (RT) and the dual-path platform (DPP) assay, were evaluated using naturally infected SAC. The study population included 156 alpacas and 175 llamas in Great Britain, Switzerland, and the United States. TB due toM. bovis(n= 44) orM. microti(n= 8) in 35 alpacas and 17 llamas was diagnosed by gross pathology examination and culture. Control animals were from herds with no TB history. The RT and the DPP assay showed sensitivities of 71% and 74%, respectively, for alpacas, while the sensitivity for llamas was 77% for both assays. The specificity of the DPP assay (98%) was higher than that of RT (94%) for llamas; the specificities of the two assays were identical (98%) for alpacas. When the two antibody tests were combined, the parallel-testing interpretation (applied when either assay produced a positive result) enhanced the sensitivities of antibody detection to 89% for alpacas and 88% for llamas but at the cost of lower specificities (97% and 93%, respectively), whereas the serial-testing interpretation (applied when both assays produced a positive result) maximized the specificity to 100% for both SAC species, although the sensitivities were 57% for alpacas and 65% for llamas. Over 95% of the animals with evidence of TB failed to produce skin test reactions, thus confirming concerns about the validity of this method for testing SAC. The findings suggest that serological assays may offer a more accurate and practical alternative for antemortem detection of camelid TB.
“Mycobacterium tilburgii” Infection in Two Immunocompromised Children: Importance of Molecular Tools in Culture-Negative Mycobacterial Disease Diagnosis
Authors: Hartwig Nico G. , Warris Adilia , van de Vosse Esther , van der Zanden Adri G. M. , Schülin-Casonato Tanja , van Ingen Jakko , van Hest Rob 
Published: October 2011

ABSTRACT

“
Mycobacterium tilburgii
” is a nontuberculous mycobacterium that cannot be cultured by current techniques. It is described as causing disseminated disease in adults. We present the first cases of disseminated disease in 2 immunocompromised children. This paper stresses the importance of molecular techniques for correct mycobacterial identification and guidance to immunological diagnosis.
Epidemiology and Antifungal Susceptibility of Bloodstream Fungal Isolates in Pediatric Patients: a Spanish Multicenter Prospective Survey
Authors: Pemán Javier , Cantón Emilia , Linares-Sicilia María José , Roselló Eva María , Borrell Nuria , Ruiz-Pérez-de-Pipaon María Teresa , Guinea Jesús , García Julio , Porras Aurelio , García-Tapia Ana María , Pérez-del-Molino Luisa , Suárez Anabel , Alcoba Julia , García-García Inmaculada 
Published: October 2011

ABSTRACT

Data on fungemia epidemiology and antifungal susceptibility of isolates from children are scarce, leading frequently to pediatric empirical treatment based on available adult data. The present study was designed to update the epidemiological, mycological, and
in vitro
susceptibility data on fungal isolates from children with fungemia in Spain. All fungemia episodes were identified prospectively by blood culture over 13 months at 30 hospitals. Tests of susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, and micafungin were performed at participant institutions by a microdilution colorimetric method. New species-specific clinical breakpoints for fluconazole, voriconazole, and echinocandins were also applied. A total of 203 episodes of fungemia in 200 children were identified. A higher proportion of fungal isolates was from general wards than intensive care units (ICU).
Candida parapsilosis
(46.8%),
Candida albicans
(36.5%),
Candida tropicalis
(5.9%),
Candida glabrata
(3.9%), and
Candida guilliermondii
(2.5%) were the leading species.
C. parapsilosis
was the predominant species except in neonates.
C. albicans
was the most frequent in neonatal ICU settings (51.9%). Intravascular catheter (79.3%), surgery (35%), prematurity (30%), and neutropenia (11%) were the most frequent predisposing factors. Most
Candida
isolates (95.1%) were susceptible to all antifungals. When the new species-specific clinical breakpoints were applied, all
C. parapsilosis
isolates were susceptible to echinocandins except one, which was micafungin resistant. This is the largest published series of fungemia episodes in the pediatric setting.
C. parapsilosis
is the most prevalent species in Spain, followed by
C. albicans
and
C. tropicalis
. Resistance to azole and echinocandin agents is extremely rare among
Candida
species. The fluconazole resistance rate in Spain has decreased in the last 10 years.
Validation of 24-Hour Flucytosine MIC Determination by Comparison with 48-Hour Determination by the Clinical and Laboratory Standards Institute M27-A3 Broth Microdilution Reference Method
Authors: Lockhart Shawn R. , Bolden Carol B. , Iqbal Naureen , Kuykendall Randall J. 
Published: October 2011

ABSTRACT

Flucytosine and itraconazole are the only antifungal agents for which the Clinical Laboratory and Standards Institute recommendations include MIC breakpoint readings at 48 h only. Here we show good essential and categorical agreement between the flucytosine MIC readings at 48 and 24 h for
Candida
species.
Down-Modulation of CD8αβ Is a Fundamental Activity of Primate Lentiviral Nef Proteins
Authors: Heigele Anke , Schindler Michael , Gnanadurai Clement W. , Leonard Jolie A. , Collins Kathleen L. , Kirchhoff Frank 
Published: October 2011

ABSTRACTIt is well established that the Nef proteins of human and simian immunodeficiency viruses (HIV and SIV) modulate major histocompatibility complex class I (MHC-I) cell surface expression to protect infected cells against lysis by cytotoxic T lymphocytes (CTLs). Recent data supported the observation that Nef also manipulates CTLs directly by down-modulating CD8αβ (J. A. Leonard, T. Filzen, C. C. Carter, M. Schaefer, and K. L. Collins, J. Virol. 85:6867–6881, 2011), but it remained unknown whether this Nef activity is conserved between different lineages of HIV and SIV. In this study, we examined a total of 42nefalleles from 16 different primate lentiviruses representing most major lineages of primate lentiviruses, as well as nonpandemic HIV-1 strains and the direct precursors of HIV-1 (SIVcpz and SIVgor). We found that the vast majority of thesenefalleles strongly down-modulate CD8β in human T cells. Primate lentiviral Nefs generally interacted specifically with the cytoplasmic tail of CD8β, and down-modulation of this receptor was dependent on the conserved dileucine-based motif and two adjacent acidic residues (DD/E) in the C-terminal flexible loop of SIV Nef proteins. Both of these motifs are known to be important for the interaction of HIV-1 Nef with AP-2, and they were also shown to be critical for down-modulation of CD4 and CD28, but not MHC-I, by SIV Nefs. Our results show that down-modulation of CD4, CD8β, and CD28 involves largely overlapping (but not identical) domains and is most likely dependent on conserved interactions of primate lentiviral Nefs with cellular adaptor proteins. Furthermore, our data demonstrate that Nef-mediated down-modulation of CD8αβ is a fundamental property of primate lentiviruses and suggest that direct manipulation of CD8+T cells plays a relevant role in viral immune evasion.
A Recombinant Chimeric La Crosse Virus Expressing the Surface Glycoproteins of Jamestown Canyon Virus Is Immunogenic and Protective against Challenge with either Parental Virus in Mice or Monkeys
Authors: Bennett R. S. , Gresko A. K. , Nelson J. T. , Murphy B. R. , Whitehead S. S. 
Published: October 2011

ABSTRACT

La Crosse virus (LACV) and Jamestown Canyon virus (JCV), family
Bunyaviridae
, are mosquito-borne viruses that are endemic in North America and recognized as etiologic agents of encephalitis in humans. Both viruses belong to the California encephalitis virus serogroup, which causes 70 to 100 cases of encephalitis a year. As a first step in creating live attenuated viral vaccine candidates for this serogroup, we have generated a recombinant LACV expressing the attachment/fusion glycoproteins of JCV. The JCV/LACV chimeric virus contains full-length S and L segments derived from LACV. For the M segment, the open reading frame (ORF) of LACV is replaced with that derived from JCV and is flanked by the untranslated regions of LACV. The resulting chimeric virus retained the same robust growth kinetics in tissue culture as observed for either parent virus, and the virus remains highly infectious and immunogenic in mice. Although both LACV and JCV are highly neurovirulent in 21 day-old mice, with 50% lethal dose (LD
50
) values of 0.1 and 0.5 log
10
PFU, respectively, chimeric JCV/LACV is highly attenuated and does not cause disease even after intracerebral inoculation of 10
3
PFU. Parenteral vaccination of mice with 10
1
or 10
3
PFU of JCV/LACV protected against lethal challenge with LACV, JCV, and Tahyna virus (TAHV). The chimeric virus was infectious and immunogenic in rhesus monkeys and induced neutralizing antibodies to JCV, LACV, and TAHV. When vaccinated monkeys were challenged with JCV, they were protected against the development of viremia. Generation of highly attenuated yet immunogenic chimeric bunyaviruses could be an efficient general method for development of vaccines effective against these pathogenic viruses.
Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins
Authors: Li Fang , Ryu Byoung Y. , Krueger Robin L. , Heldt Scott A. , Albritton Lorraine M. 
Published: October 2011

ABSTRACT

Here we report a novel viral glycoprotein created by replacing a natural receptor-binding sequence of the ecotropic Moloney murine leukemia virus envelope glycoprotein with the peptide ligand somatostatin. This new chimeric glycoprotein, which has been named the Sst receptor binding site (Sst-RBS), gives targeted transduction based on three criteria: (i) a gain of the use of a new entry receptor not used by any known virus; (ii) targeted entry at levels comparable to gene delivery by wild-type ecotropic Moloney murine leukemia virus and vesicular stomatitis virus (VSV) G glycoproteins; and (iii) a loss of the use of the natural ecotropic virus receptor. Retroviral vectors coated with Sst-RBS gained the ability to bind and transduce human 293 cells expressing somatostatin receptors. Their infection was specific to target somatostatin receptors, since a synthetic somatostatin peptide inhibited infection in a dose-dependent manner and the ability to transduce mouse cells bearing the natural ecotropic receptor was effectively lost. Importantly, vectors coated with the Sst-RBS glycoprotein gave targeted entry of up to 1 × 10
6
transducing U/ml, a level comparable to that seen with infection of vectors coated with the parental wild-type ecotropic Moloney murine leukemia virus glycoprotein through the ecotropic receptor and approaching that of infection of VSV G-coated vectors through the VSV receptor. To our knowledge, this is the first example of a glycoprotein that gives targeted entry of retroviral vectors at levels comparable to the natural capacity of viral envelope glycoproteins.
The Oral Secretion of Infectious Scrapie Prions Occurs in Preclinical Sheep with a Range of
PRNP
Genotypes
Authors: Gough Kevin C. , Baker Claire A. , Rees Helen C. , Terry Linda A. , Spiropoulos John , Thorne Leigh , Maddison Ben C. 
Published: October 2011

ABSTRACT

Preclinical sheep with the highly scrapie-susceptible VRQ/VRQ
PRNP
genotype secrete prions from the oral cavity. In order to further understand the significance of orally available prions, buccal swabs were taken from sheep with a range of
PRNP
genotypes and analyzed by serial protein misfolding cyclic amplification (sPMCA). Prions were detected in buccal swabs from scrapie-exposed sheep of genotypes linked to high (VRQ/VRQ and ARQ/VRQ) and low (ARR/VRQ and AHQ/VRQ) lymphoreticular system involvement in scrapie pathogenesis. For both groups, the level of prion detection was significantly higher than that for scrapie-resistant ARR/ARR sheep which were kept in the same farm environment and acted as sentinel controls for prions derived from the environment which might contaminate the oral cavity. In addition, sheep with no exposure to the scrapie agent did not contain any measurable prions within the oral cavity. Furthermore, prions were detected in sheep over a wide age range representing various stages of preclinical disease. These data demonstrate that orally available scrapie prions may be a common feature in sheep incubating scrapie, regardless of the
PRNP
genotype and any associated high-level accumulation of PrP
Sc
within lymphoreticular tissues. PrP
Sc
was present in buccal swabs from a large proportion of sheep with
PRNP
genotypes associated with relatively low disease penetrance, indicating that subclinical scrapie infection is likely to be a common occurrence. The significance of positive sPMCA reactions was confirmed by the transmission of infectivity in buccal swab extracts to Tg338 mice, illustrating the likely importance of orally available prions in the horizontal transmission of scrapie.
Herpes Simplex Virus Requires Poly(ADP-Ribose) Polymerase Activity for Efficient Replication and Induces Extracellular Signal-Related Kinase-Dependent Phosphorylation and ICP0-Dependent Nuclear Localization of Tankyrase 1
Authors: Li Zhuan , Yamauchi Yohei , Kamakura Maki , Murayama Tsugiya , Goshima Fumi , Kimura Hiroshi , Nishiyama Yukihiro 
Published: October 2011

ABSTRACT
Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) which localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Poly(ADP-ribosyl)ation of the nuclear mitotic apparatus (NuMA) protein by tankyrase 1 during mitosis is essential for sister telomere resolution and mitotic spindle pole formation. In interphase cells, tankyrase 1 resides in the cytoplasm, and its role therein is not well understood. In this study, we found that herpes simplex virus (HSV) infection induced extensive modification of tankyrase 1 but not tankyrase 2. This modification was dependent on extracellular signal-regulated kinase (ERK) activity triggered by HSV infection. Following HSV-1 infection, tankyrase 1 was recruited to the nucleus. In the early phase of infection, tankyrase 1 colocalized with ICP0 and thereafter localized within the HSV replication compartment, which was blocked in cells infected with the HSV-1 ICP0-null mutant R7910. In the absence of infection, ICP0 interacted with tankyrase 1 and efficiently promoted its nuclear localization. HSV did not replicate efficiently in cells depleted of both tankyrases 1 and 2. Moreover, XAV939, an inhibitor of tankyrase PARP activity, decreased viral titers to 2 to 5% of control values. We concluded that HSV targets tankyrase 1 in an ICP0- and ERK-dependent manner to facilitate its replication.
Reconstitution of the Kaposi's Sarcoma-Associated Herpesvirus Nuclear Egress Complex and Formation of Nuclear Membrane Vesicles by Coexpression of ORF67 and ORF69 Gene Products
Authors: Desai Prashant J. , Pryce Erin N. , Henson Brandon W. , Luitweiler Eric M. , Cothran Jonathan 
Published: October 2011

ABSTRACT
The Kaposi's sarcoma-associated herpesvirus nuclear egress complex is composed of two proteins, ORF67 and ORF69. In this study, we have recapitulated the KSHV complex by coexpression of these two proteins in insect cells using expression from recombinant baculoviruses. The proteins form a complex at the nuclear membrane as judged by live-cell analysis of protein fusions tagged with green fluorescent protein (GFP) and mCherry. Ultrastructural analysis of infected cells showed that ORF67 expression results in reduplication of the nuclear membrane. When the two proteins are expressed together, numerous virion-size nuclear membrane-derived vesicles were evident at the nuclear margins.
The emergency first aid responder system model: using community members to assist life-threatening emergencies in violent, developing areas of need
Authors: Sun Jared H , Wallis Lee A 
Published: October 2011

BackgroundAs many as 90% of all trauma-related deaths occur in developing nations, and this is expected to get worse with modernisation. The current method of creating an emergency care system by modelling after that of a Western nation is too resource-heavy for most developing countries to handle. A cheaper, more community-based model is needed to establish new emergency care systems and to support them to full maturity.MethodsA needs assessment was undertaken in Manenberg, a township in Cape Town with high violence and injury rates. Community leaders and successfully established local services were consulted for the design of a first responder care delivery model. The resultant community-based emergency first aid responder (EFAR) system was implemented, and EFARs were tracked over time to determine skill retention and usage.ResultsThe EFAR system model and training curriculum. Basic EFARs are spread throughout the community with the option of becoming stationed advanced EFARs. All EFARs are overseen by a local organisation and a professional body, and are integrated with the local ambulance response if one exists. On competency examinations, all EFARs tested averaged 28.2% before training, 77.8% after training, 71.3% 4 months after training and 71.0% 6 months after training. EFARs reported using virtually every skill taught them, and further review showed that they had done so adequately.ConclusionThe EFAR system is a low-cost, versatile model that can be used in a developing region both to lay the foundation for an emergency care system or support a new one to maturity.
Should lymph nodes from colorectal cancer resection specimens be processed in their entirety?
Authors: Ervine Aaron , Houghton Joe , Park Richard 
Published: October 2011

AimsTo quantify the benefit of processing each lymph node in its entirety in colorectal cancer specimens.Methods391 consecutive cases were examined retrospectively to assess how often cases were upstaged to node positive disease by examining each node in its entirety.Results7 out of 391 patients were upstaged by this method. However, of those patients, approximately three could have been detected by chance. Therefore, approximately 1% of cases were correctly upstaged. However, six of these seven patients also had at least one additional adverse prognostic factor, and would otherwise have been considered high risk Dukes' B cases.ConclusionsProcessing all slices of each lymph node significantly increases laboratory workload and is of minimal clinical benefit.
P16INK4Aoverexpression predicts lymph node metastasis in cervical carcinomas
Authors: Huang Lee-Wen , Lee Chin-Cheng 
Published: October 2011

BackgroundThe p16INK4Aprotein (p16) is a cyclin-dependent kinase inhibitor that arrests the cell cycle in the G1 phase.AimTo explore the potential of p16 as a predictive marker for lymph node (LN) metastasis and prognosis in cervical carcinomas.Methods145 patients diagnosed with FIGO stage I to IV cervical carcinoma were studied; 95 underwent LN dissection. The expression of p16 protein was studied by immunohistochemistry using tissue microarrays.ResultsOverexpression of p16 was seen in 108 of 145 (74.5%) invasive carcinomas. There was a significant correlation between p16 expression and LN metastasis (p=0.007). Patients with p16 overexpression had poorer survival than patients with p16 underexpression (59.3% vs 83.8% 5-year survival rate, log-rank p=0.015). In univariate analysis, p16 expression was a significant predictor of survival (RR 2.76, p=0.02).ConclusionsResults suggest that p16 expression is an important predictive factor of LN metastasis in cervical cancer patients. Moreover, p16 overexpression is associated with a poor prognosis. Therefore, immunohistochemical evaluation of p16 expression is of potential value for treatment planning in cervical carcinomas.
Why is housing tenure associated with a lower risk of admission to a nursing or residential home? Wealth, health and the incentive to keep ‘my home’
Authors: McCann Mark , Grundy Emily , O'Reilly Dermot 
Published: October 2011

BackgroundPrevious research has shown that home ownership is associated with a reduced risk of admission to institutional care. The extent to which this reflects associations between wealth and health, between wealth and ability to buy in care or increased motivation to avoid admission related to policies on charging is unclear. Taking account of the value of the home, as well as housing tenure, may provide some clarification as to the relative importance of these factors.AimsTo analyse the probability of admission to residential and nursing home care according to housing tenure and house value.MethodsCox regression was used to examine the association between home ownership, house value and risk of care home admissions over 6 years of follow-up among a cohort of 51 619 people aged 65 years or older drawn from the Northern Ireland Longitudinal Study, a representative sample of ≈28% of the population of Northern Ireland.Results4% of the cohort (2138) was admitted during follow-up. Homeowners were less likely than those who rented to be admitted to care homes (HR 0.77, 95% CI 0.70 to 0.85, after adjusting for age, sex, health, living arrangement and urban/rural differences). There was a strong association between house value/tenure and health with those in the highest valued houses having the lowest odds of less than good health or limiting long-term illness. However, there was no difference in probability of admission according to house value; HRs of 0.78 (95% CI 0.67 to 0.90) and 0.81 (95% CI 0.70 to 0.95), respectively, for the lowest and highest value houses compared with renters.ConclusionsThe requirement for people in the UK with capital resources to contribute to their care is a significant disincentive to institutional admission. This may place an additional burden on carers.