bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron status in infants with alloimmune haemolytic disease in the first three months of life
Authors: Rath M. E. A. , Smits‐Wintjens V. E. H. J. , Oepkes D. , Walther F. J. , Lopriore E. 
Published: June 2013

Background and ObjectivesFerritin levels are often highly elevated at birth in neonates with alloimmune haemolytic disease of the fetus and newborn (HDFN). Data on ferritin levels in these infants in the first 3 months of life are lacking. Objective of this study was to examine the course of iron status and incidence of iron deficiency and overload in neonates with alloimmune HDFN up to 3 months of age. Secondary objective was to analyse bilirubin levels, liver enzymes and red‐blood‐cell indices in the same time period and the association with intrauterine transfusion (IUT).Materials and MethodsObservational study of neonates with alloimmune HDFN admitted to our centre between November 2010 and March 2012. Data on iron status, bilirubin levels, liver enzymes and red‐blood‐cell indices up to 3 months of age were routinely collected and compared between neonates treated with and without IUT.ResultsThirty‐five infants with alloimmune HDFN were included. Iron overload occurred in 70% of neonates at birth and in 50% and 18% at the age of 1 and 3 months, respectively. No cases of iron deficiency at birth and only one case of iron deficiency at 3 months of age were found. No infants received iron therapy. Infants who received IUT had a significantly lower haemoglobin level and reticulocyte count and higher ferritin level at birth.ConclusionThe vast majority of neonates with alloimmune HDFN have iron overload at birth. Incidence of iron overload gradually decreases within the first 3 months without iron supplementation.
Allergic transfusion reactions to platelets are more commonly associated with prepooled than apheresis components
Authors: Xiao W. , Tormey C. A. , Capetillo A. , Maitta R. W. 
Published: June 2013

Background and ObjectivesTransfusions of pooled or apheresis platelets are seen as equally effective in increasing platelet counts with similar rates of transfusion reactions. It has been suggested that allergic transfusion reactions (ATRs) to platelets are associated with recipient and donor factors. In this study, we assessed differences in ATR rates among individuals who received platelet components at two academic medical centres.Materials and MethodsA total of 45 189 leukoreduced platelet products were transfused during the study period of which 31 748 were apheresis units and 13 441 were pooled units.ResultsTransfusion reactions were reported in 0·6% (277 of 45 189) of platelet transfusions. The reaction rate was significantly higher in pooled (102 of 13 441) than in apheresis (175 of 31 748) (0·76% vs. 0·55%, respectively, P = 0·01) components. However, an analysis of reactions by categories indicated that only the ATR rate was significantly higher in pooled (55 of 13 441) products as compared with apheresis (76 of 31 748) (0·41% vs. 0·24%, respectively, P = 0·0029) platelets. Moreover, there was no difference in the rate of ABO mismatch between pooled and apheresis products.ConclusionOur data indicate that pooled platelet components are associated with higher ATR rates than apheresis platelets, suggesting that these components may not be completely equivalent from the standpoint of adverse events. Further investigation is needed to address whether differences in ATRs are related to the pooling process or the extent of donor antigen exposure.
MICRONODULAR ULTRASOUND LESIONS IN THE COLONIC SUBMUCOSA OF 42 DOGS AND 14 CATS
Authors: Citi Simonetta , Chimenti Tommaso , Marchetti Veronica , Millanta Francesca , Mannucci Tommaso 
Published: June 2013

Micronodular ultrasound lesions have been detected in the colonic submucosa of dogs and cats at our hospital. The lesions had rounded/oval shapes, measured 1–3 mm in size, and exhibited a hypo/anechoic ultrasonographic pattern. To our knowledge, these lesions have not been previously reported in human or veterinary patients. The purpose of this retrospective study was to determine whether micronodular lesions were associated with other abdominal ultrasound abnormalities or clinical findings. Medical records of dogs and cats with sonographic reports describing micronodular lesions within the colonic submucosa were reviewed. Concurrent ultrasonographic abnormalities were recorded and compared with clinical sidgns and follow‐up data. A total of 42 dogs and 14 cats met inclusion criteria. Concurrent sonographic abnormalities included the following: increased colon wall thickness (12.5%); small bowel wall thickening, altered layering, and/or hyperechoic mucosa (45%); abdominal effusion (29%); caudal mesenteric lymphadenopathy (46%); mesenteric lymphadenopathy (27%); and pericolic peritoneal fat reactivity (9%). Fifty of 56 animals presented with diarrhea. Twenty‐seven cases had clinical signs of colitis and ultrasonographic lesions were limited to the colonic submucosa. In nine cases, follow‐up examination at 6–8 weeks showed resolution of clinical and ultrasonographic signs. Ultrasonographic and clinical examinations in 17 patients at 12–18 months and in 20 patients at 18–30 months from initial diagnosis showed resolution of submucosal lesions and clinical signs of enteropathy. The authors propose that micronodular submucosal ultrasound lesions may represent reactive intraparietal lymphoid follicles and may be indicators of colonic inflammatory diseases in dogs and cats.
Genetic Distribution of Noncapsular Meningococcal Group B Vaccine Antigens in Neisseria lactamica
Authors: Lucidarme Jay , Gilchrist Stefanie , Newbold Lynne S. , Gray Stephen J. , Kaczmarski Edward B. , Richardson Lynne , Bennett Julia S. , Maiden Martin C. J. , Findlow Jamie , Borrow Ray 
Published: June 2013

ABSTRACT

The poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp),
Neisseria
adhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (
Neisseria meningitidis
); however, many subcapsular antigens are shared with nonpathogenic members of the genus
Neisseria
that also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal,
Neisseria lactamica
. All the isolates possessed
nhba
but were devoid of
fhbp
and
nadA
. The
nhba
alleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented.
Role of Antilipopolysaccharide Antibodies in Serum Bactericidal Activity against Salmonella enterica Serovar Typhimurium in Healthy Adults and Children in the United States
Authors: Trebicka Estela , Jacob Susan , Pirzai Waheed , Hurley Bryan P. , Cherayil Bobby J. 
Published: June 2013

ABSTRACTRecent observations from Africa have rekindled interest in the role of serum bactericidal antibodies in protecting against systemic infection withSalmonella entericaserovar Typhimurium. To determine whether the findings are applicable to other populations, we analyzed serum samples collected from healthy individuals in the United States. We found that all but 1 of the 49 adult samples tested had robust bactericidal activity againstS. Typhimurium in a standardin vitroassay. The activity was dependent on complement and could be reproduced by immunoglobulin G (IgG) purified from the sera. The bactericidal activity was inhibited by competition with soluble lipopolysaccharide (LPS) fromS. Typhimurium but not fromEscherichia coli, consistent with recognition of a determinant in the O-antigen polysaccharide. Sera from healthy children aged 10 to 48 months also had bactericidal activity, although it was significantly less than in the adults, correlating with lower levels of LPS-specific IgM and IgG. The lone sample in our collection that lacked bactericidal activity was able to inhibit killing ofS. Typhimurium by the other sera. The inhibition correlated with the presence of an LPS-specific IgM and was associated with decreased complement deposition on the bacterial surface. Our results indicate that healthy individuals can have circulating antibodies to LPS that either mediate or inhibit killing ofS. Typhimurium. The findings contrast with the observations from Africa, which linked bactericidal activity to antibodies against anS. Typhimurium outer membrane protein and correlated the presence of inhibitory anti-LPS antibodies with human immunodeficiency virus infection.
Evaluation of a New Automated Homogeneous PCR Assay, GenomEra C. difficile, for Rapid Detection of Toxigenic Clostridium difficile in Fecal Specimens
Authors: Hirvonen Jari J. , Mentula Silja , Kaukoranta Suvi-Sirkku 
Published: June 2013

ABSTRACT

We evaluated a new automated homogeneous PCR assay to detect toxigenic
Clostridium difficile
, the GenomEra
C. difficile
assay (Abacus Diagnostica, Finland), with 310 diarrheal stool specimens and with a collection of 33 known clostridial and nonclostridial isolates. Results were compared with toxigenic culture results, with discrepancies being resolved by the GeneXpert
C. difficile
PCR assay (Cepheid). Among the 80 toxigenic culture-positive or GeneXpert
C. difficile
assay-positive fecal specimens, 79 were also positive with the GenomEra
C. difficile
assay. Additionally, one specimen was positive with the GenomEra assay but negative with the confirmatory methods. Thus, the sensitivity and specificity were 98.8% and 99.6%, respectively. With the culture collection, no false-positive or -negative results were observed. The analytical sensitivity of the GenomEra
C. difficile
assay was approximately 5 CFU per PCR test. The short hands-on (<5 min for 1 to 4 samples) and total turnaround (<1 h) times, together with the high positive and negative predictive values (98.8% and 99.6%, respectively), make the GenomEra
C. difficile
assay an excellent option for toxigenic
C. difficile
detection in fecal specimens.
New Rapid Scheme for Distinguishing the Subspecies of the Mycobacterium abscessus Group and Identifying Mycobacterium massiliense Isolates with Inducible Clarithromycin Resistance
Authors: Shallom Shamira J. , Gardina Paul J. , Myers Timothy G. , Sebastian Yinong , Conville Patricia , Calhoun Leslie B. , Tettelin Hervé , Olivier Kenneth N. , Uzel Gulbu , Sampaio Elizabeth P. , Holland Steven M. , Zelazny Adrian M. 
Published: June 2013

ABSTRACT

Mycobacterium abscessus
(
M. abscessus
sensu lato, or the
M. abscessus
group) comprises three closely related taxa whose taxonomic statuses are under revision, i.e.,
M. abscessus
sensu stricto,
Mycobacterium bolletii
, and
Mycobacterium massiliense
. We describe here a simple, robust, and cost-effective PCR-based method for distinguishing among
M. abscessus
,
M. massiliense
, and
M. bolletii
. Based on the
M. abscessus
ATCC 19977
T
genome, regions that discriminated between
M. abscessus
and
M. massiliense
were identified through array-based comparative genomic hybridization. A typing scheme using PCR primers designed for four of these locations was applied to 46 well-characterized clinical isolates comprising 29
M. abscessus
, 15
M. massiliense
, and 2
M. bolletii
isolates previously identified by multitarget sequencing. Interestingly, 2 isolates unequivocally identified as
M. massiliense
were shown to have a full-length
erm
(41) gene instead of the expected gene deletion and showed inducible clarithromycin resistance after 14 days. We propose using this PCR-based typing scheme combined with
erm
(41) PCR for straightforward identification of
M. abscessus
,
M. massiliense
, and
M. bolletii
and the assessment of inducible clarithromycin resistance. This method can be easily integrated into a routine workflow to provide subspecies-level identification within 24 h after isolation of the
M. abscessus
group.
Complex Reassortment of Multiple Subtypes of Avian Influenza Viruses in Domestic Ducks at the Dongting Lake Region of China
Authors: Deng Guohua , Tan Dan , Shi Jianzhong , Cui Pengfei , Jiang Yongping , Liu Liling , Tian Guobin , Kawaoka Yoshihiro , Li Chengjun , Chen Hualan 
Published: June 2013

ABSTRACT
To gain insight into the ecology of avian influenza viruses (AIV), we conducted active influenza virus surveillance in domestic ducks on farms located on the flyway of migratory birds in the Dongting Lake region of Hunan Province, China, from winter 2011 until spring 2012. Specimens comprising 3,030 duck swab samples and 1,010 environmental samples were collected from 101 duck farms. We isolated AIV of various HA subtypes, including H3, H4, H5, H6, H9, H10, H11, and H12. We sequenced the entire coding sequences of the genomes of 28 representative isolates constituting 13 specific subtypes. When the phylogenetic relationships among these isolates were examined, we observed that extensive reassortment events had occurred. Among the 28 Dongting Lake viruses, 21 genotypes involving the six internal genes were identified. Furthermore, we identified viruses or viral genes introduced from other countries, viral gene segments of unknown origin, and a novel HA/NA combination. Our findings emphasize the importance of farmed domestic ducks in the Dongting Lake region to the genesis and evolution of AIV and highlight the need for continued surveillance of domestic ducks in this region.
A Cholesterol Tag at the N Terminus of the Relatively Broad-Spectrum Fusion Inhibitory Peptide Targets an Earlier Stage of Fusion Glycoprotein Activation and Increases the Peptide's Antiviral Potency
In Vivo
Authors: Li Chuan-Gen , Tang Wang , Chi Xiao-Jing , Dong Zhi-Ming , Wang Xi-Xi , Wang Xiao-Jia 
Published: June 2013

ABSTRACT

In previous work, we designed peptides that showed potent inhibition of Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) infections in chicken embryos. In this study, we demonstrate that peptides modified with cholesterol or 3 U of polyethylene glycol (PEG
3
) conjugated to the peptides' N termini showed even more promising antiviral activities when tested in animal models. Both cholesterol- and cholesterol-PEG
3
-tagged peptides were able to protect chicken embryos from infection with different serotypes of NDV and IBV when administered 12 h prior to virus inoculation. In comparison, the untagged peptides required intervention closer to the time of viral inoculation to achieve a similar level of protection. Intramuscular injection of cholesterol-tagged peptide at 1.6 mg/kg 1 day before virus infection and then three times at 3-day intervals after viral inoculation protected 70% of the chickens from NDV infection. We further demonstrate that the cholesterol-tagged peptide has an
in vivo
half-life greater than that of untagged peptides. It also has the potential to cross the blood-brain barrier to enter the avian central nervous system (CNS). Finally, we show that the cholesterol-tagged peptide could play a role before the viral fusion peptide's insertion into the host cell and thereby target an earlier stage of fusion glycoprotein activation. Our findings are of importance for the further development of antivirals with broad-spectrum protective effects.
Latent HIV-1 Can Be Reactivated by Cellular Superinfection in a Tat-Dependent Manner, Which Can Lead to the Emergence of Multidrug-Resistant Recombinant Viruses
Authors: Donahue Daniel A. , Bastarache Sophie M. , Sloan Richard D. , Wainberg Mark A. 
Published: June 2013

ABSTRACT
The HIV-1 latent reservoir represents an important source of genetic diversity that could contribute to viral evolution and multidrug resistance following latent virus reactivation. This could occur by superinfection of a latently infected cell. We asked whether latent viruses might be reactivated when their host cells are superinfected, and if so, whether they could contribute to the generation of recombinant viruses. Using populations of latently infected Jurkat cells, we found that latent viruses were efficiently reactivated upon superinfection. Pathways leading to latent virus reactivation via superinfection might include gp120-CD4/CXCR4-induced signaling, modulation of the cellular environment by Nef, and/or the activity of Tat produced upon superinfection. Using a range of antiviral compounds and genetic approaches, we show that gp120 and Nef are not required for latent virus reactivation by superinfection, but this process depends on production of functional Tat by the superinfecting virus. In a primary cell model of latency in unstimulated CD4 T cells, superinfection also led to latent virus reactivation. Drug-resistant latent viruses were also reactivated following superinfection in Jurkat cells and were able to undergo recombination with the superinfecting virus. Under drug-selective pressure, this generated multidrug-resistant recombinants that were identified by unique restriction digestion band patterns and by population-level sequencing. During conditions of poor drug adherence, treatment interruption or treatment failure, or in drug-impermeable sanctuary sites, reactivation of latent viruses by superinfection or other means could provide for the emergence or spread of replicatively fit viruses in the face of strong selective pressures.
Lichen monitoring as a potential tool in environmental forensics: case study of the Cu smelter and former mining town of Karabash, Russia
Authors: Purvis O. W. , Williamson B. J. , Spiro B. , Udachin V. , Mikhailova I. N. , Dolgopolova A. 
Published: June 2013

Abstract

The aim of this paper is to showcase the use of lichens in environmental forensics from an assessment of atmospheric deposition in and around the Cu smelter and former mining town of Karabash, Ural Mountains of Russia.
Hypogymnia physodes
was collected on its bark substrate in July 2001 from a ‘reference’ site (
c.
25 km SW of Karabash) and transplanted to 10 stations along an approximately 60 km SSW–NNE transect centred on Karabash. Transplants were collected after 2 and 3 month exposure periods. The elemental compositions of
Hypogymnia
and potential sources of particulates in the study area (smelter blast furnace and converter dusts, wastes, tailings, road dusts, metallurgical slags and top soils) were determined by inductively coupled plasma optical emission spectrometry (ICP-OES) and quadrupole ICP mass spectrometry (ICP-MS), and the Pb isotope compositions of the lichens and smelter dusts by multicollector ICP-MS. Particulates on lichen surfaces were analysed by scanning electron microscopy with energy-dispersive X-ray analysis (SEM-EDX).

The method of lichen transplantation, combined with multi-element and surface particle elemental analysis, high-precision Pb isotope ratio determinations and modelling, was shown to be useful for the tracing of the smelter signal, and components from different smelter processes, for more than 25 km from Karabash town. The lichen monitoring methodology is discrete and comparatively low cost, enabling atmospheric deposition from natural and anthropogenic sources to be determined over short (<3 month) periods, and is therefore a valuable qualitative tool for environmental forensics.
S49076 Is a Novel Kinase Inhibitor of MET, AXL, and FGFR with Strong Preclinical Activity Alone and in Association with Bevacizumab
Authors: Burbridge Mike F. , Bossard Céline J. , Saunier Carine , Fejes Imre , Bruno Alain , Léonce Stéphane , Ferry Gilles , Da Violante Georges , Bouzom François , Cattan Valérie , Jacquet-Bescond Anne , Comoglio Paolo M. , Lockhart Brian P. , Boutin Jean A. , Cordi Alex , Ortuno Jean-Claude , Pierré Alain , Hickman John A. , Cruzalegui Francisco H. , Depil Stéphane 
Published: June 2013

AbstractAberrant activity of the receptor tyrosine kinases MET, AXL, and FGFR1/2/3 has been associated with tumor progression in a wide variety of human malignancies, notably in instances of primary or acquired resistance to existing or emerging anticancer therapies. This study describes the preclinical characterization of S49076, a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3. S49076 potently blocked cellular phosphorylation of MET, AXL, and FGFRs and inhibited downstream signaling in vitro and in vivo. In cell models, S49076 inhibited the proliferation of MET- and FGFR2-dependent gastric cancer cells, blocked MET-driven migration of lung carcinoma cells, and inhibited colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 was established and correlated well with impact on tumor growth. MET, AXL, and the FGFRs have all been implicated in resistance to VEGF/VEGFR inhibitors such as bevacizumab. Accordingly, combination of S49076 with bevacizumab in colon carcinoma xenograft models led to near total inhibition of tumor growth. Moreover, S49076 alone caused tumor growth arrest in bevacizumab-resistant tumors. On the basis of these preclinical studies showing a favorable and novel pharmacologic profile of S49076, a phase I study is currently underway in patients with advanced solid tumors. Mol Cancer Ther; 12(9); 1749–62. ©2013 AACR.
Tissue factor expressed by microparticles is associated with mortality but not with thrombosis in cancer patients
Authors: Hernández Carmen , Orbe Josune , Roncal Carmen , Alvarez-Hernandez Maria , de Lizarrondo Sara Martinez , Alves Maria T. , Mata Jesus García , Páramo José A. 
Published: June 2013

SummaryA prothrombotic state is one of the hallmarks of malignancy and a major contributor to morbidity and mortality in cancer patients. Tissue factor (TF) is often overexpressed in malignancy and is a prime candidate in predicting the hypercoagulable state. Moreover, increased number of TF-exposing microparticles (MPs) in cancer patients may contribute to venous thromboembolism (VTE). We have conducted a prospective cohort study to determine whether elevated TF antigen, TF activity and TF associated to MPs (MPs-TF) are predictive of VTE and mortality in cancer patients. The studied population consisted of 252 cancer patients and 36 healthy controls. TF antigen and activity and MPs-TF were determined by ELISA and chromogenic assays. During a median follow-up of 10 months, 40 thrombotic events were recorded in 34 patients (13.5%), and 73 patients (28.9%) died. TF antigen and activity were significantly higher in patients than in controls (p<0.01) mainly in patients with advanced stages, whereas no differences were observed for TF activity of isolated MPs. We did not find a statistically significant association of TF variables with the risk of VTE. Multivariate analysis adjusting for age, sex, type of cancer and other confounding variables showed that TF activity (p<0.01) and MPs-TF activity (p<0.05) were independently associated with mortality. In conclusion, while TF variables were not associated with future VTE in cancer patients, we found a strong association of TF and MPs-TF activity with mortality, thus suggesting they might be good prognostic markers in cancer patients.