bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Double‐Blind Randomized Controlled Trial To Study the Efficacy of Topiramate in a Civilian Sample of PTSD
Authors: Yeh Mary S. L. , Mari Jair Jesus , Costa Mariana Caddrobi Pupo , Andreoli Sergio Baxter , Bressan Rodrigo Affonseca , Mello Marcelo Feijó 
Published: September 2010

SUMMARYObjective: To evaluate the efficacy and tolerability of topiramate in patients with posttraumatic stress disorder (PTSD). Method: We conducted a 12‐week double‐blind, randomized, placebo‐controlled study comparing topiramate to placebo. Men and women aged 18–62 years with diagnosis of PTSD according to DSM‐IV were recruited from the outpatient clinic of the violence program of Federal University of São Paulo Hospital (Prove‐UNIFESP), São Paulo City, between April 2006 and December 2009. Subjects were assessed for the Clinician‐Administered Posttraumatic Stress Scale (CAPS), Clinical Global Impression, and Beck Depression Inventory (BDI). After 1‐week period of washout, 35 patients were randomized to either group. The primary outcome measure was the CAPS total score changes from baseline to the endpoint. Results: 82.35% of patients in the topiramate group exhibited improvements in PTSD symptoms. The efficacy analysis demonstrated that patients in the topiramate group exhibited significant improvements in reexperiencing symptoms: flashbacks, intrusive memories, and nightmares of the trauma (CAPS‐B; P= 0.04) and in avoidance/numbing symptoms associated with the trauma, social isolation, and emotional numbing (CAPS‐C; P= 0.0001). Furthermore, the experimental group demonstrated a significant difference in decrease in CAPS total score (topiramate −57.78; placebo −32.41; P= 0.0076). Mean topiramate dose was 102.94 mg/d. Topiramate was generally well tolerated. Conclusion: Topiramate was effective in improving reexperiencing and avoidance/numbing symptom clusters in patients with PTSD. This study supports the use of anticonvulsants for the improvement of symptoms of PTSD.
Enzyme-Linked Immunosorbent Assay for Detection of Filovirus Species-Specific Antibodies
Authors: Nakayama Eri , Yokoyama Ayaka , Miyamoto Hiroko , Igarashi Manabu , Kishida Noriko , Matsuno Keita , Marzi Andrea , Feldmann Heinz , Ito Kimihito , Saijo Masayuki , Takada Ayato 
Published: September 2010

ABSTRACT
Several enzyme-linked immunosorbent assays (ELISAs) for the detection of filovirus-specific antibodies have been developed. However, diagnostic methods to distinguish antibodies specific to the respective species of filoviruses, which provide the basis for serological classification, are not readily available. We established an ELISA using His-tagged secreted forms of the transmembrane glycoproteins (GPs) of five different Ebola virus (EBOV) species and one Marburg virus (MARV) strain as antigens for the detection of filovirus species-specific antibodies. The GP-based ELISA was evaluated by testing antisera collected from mice immunized with virus-like particles as well as from humans and nonhuman primates infected with EBOV or MARV. In our ELISA, little cross-reactivity of IgG antibodies was observed in most of the mouse antisera. Although sera and plasma from some patients and monkeys showed notable cross-reactivity with the GPs from multiple filovirus species, the highest reactions of IgG were uniformly detected against the GP antigen homologous to the virus species that infected individuals. We further confirmed that MARV-specific IgM antibodies were specifically detected in specimens collected from patients during the acute phase of infection. These results demonstrate the usefulness of our ELISA for diagnostics as well as ecological and serosurvey studies.
Characterization of Pneumonia Due toStreptococcus equisubsp.zooepidemicusin Dogs
Authors: Priestnall Simon L. , Erles Kerstin , Brooks Harriet W. , Cardwell Jacqueline M. , Waller Andrew S. , Paillot Romain , Robinson Carl , Darby Alistair C. , Holden Matthew T. G. , Schöniger Sandra 
Published: September 2010

ABSTRACTStreptococcus equisubsp.zooepidemicushas been linked to cases of acute fatal pneumonia in dogs in several countries. Outbreaks can occur in kenneled dog populations and result in significant levels of morbidity and mortality. This highly contagious disease is characterized by the sudden onset of clinical signs, including pyrexia, dyspnea, and hemorrhagic nasal discharge. The pathogenesis ofS. equisubsp.zooepidemicusinfection in dogs is poorly understood. This study systematically characterized the histopathological changes in the lungs of 39 dogs from a large rehoming shelter in London, United Kingdom; the dogs were infected withS. equisubsp.zooepidemicus. An objective scoring system demonstrated thatS. equisubsp.zooepidemicuscaused pneumonia in 26/39 (66.7%) dogs, and most of these dogs (17/26 [65.4%]) were classified as severe fibrino-suppurative, necrotizing, and hemorrhagic. Three recently described superantigen genes (szeF,szeN, andszeP) were detected by PCR in 17/47 (36.2%) of theS. equisubsp.zooepidemicusisolates; however, there was no association between the presence of these genes and the histopathological score. The lungs ofS. equisubsp.zooepidemicus-infected dogs with severe respiratory signs and lung pathology did however have significantly higher mRNA levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8) than in uninfected controls, suggesting a role for an exuberant host immune response in the pathogenesis of this disease.
Comparison of the
Babesia duncani
(WA1) IgG Detection Rates among Clinical Sera Submitted to a Reference Laboratory for WA1 IgG Testing and Blood Donor Specimens from Diverse Geographic Areas of the United States
Authors: Prince Harry E. , Lapé-Nixon Mary , Patel Hemlata , Yeh Cindy 
Published: September 2010

ABSTRACT

All reported cases of WA1 babesiosis have occurred in the Pacific coast region of the United States, suggesting that WA1 is limited to this geographic area. However, we detected WA1 IgG in 27% of clinical sera sent to our laboratory for WA1 IgG testing from across the United States over a 2-year period, suggesting that exposure to WA1 or a closely related organism occurs outside Pacific coast states. We sought to determine if this high WA1 IgG detection rate among clinical specimens merely reflects WA1 seroprevalence outside the Pacific region. WA1 IgG, as well as
Babesia microti
IgG, was measured in 900 blood donor specimens from 9 states. Overall seroprevalence was 2.0% for WA1 and 0.4% for
B. microti
; regional seroprevalences ranged from 0 to 4% and 0 to 2%, respectively. Additional studies were performed to determine if WA1 IgG reactivity was attributable to polyclonal B-cell activation associated with acute Epstein-Barr virus (EBV) infection; 40 WA1 IgG-positive clinical sera and the 18 WA1 IgG-positive blood donor specimens were all negative for EBV capsid antigen (EBVCA) IgM (a marker of acute EBV infection), and 40 EBVCA IgM-positive sera were all negative for WA1 IgG. These findings indicate that the high WA1 IgG detection rate among clinical specimens does not simply reflect the national WA1 seroprevalence among blood donors or nonspecific reactivity due to acute EBV infection. Rather, the findings suggest that infection with WA1 or a related organism is more common than indicated by the literature and is not limited to Pacific coast states.
A Single, Engineered Protein Therapeutic Agent Neutralizes Exotoxins from BothStaphylococcus aureusandStreptococcus pyogenes
Authors: Wang Ningyan , Mattis Daiva M. , Sundberg Eric J. , Schlievert Patrick M. , Kranz David M. 
Published: September 2010

ABSTRACTStaphylococcus aureusandStreptococcus pyogenessecrete exotoxins that act as superantigens, proteins that cause hyperimmune reactions by binding the variable domain of the T-cell receptor beta chain (Vβ), leading to stimulation of a large fraction of the T-cell repertoire. To develop potential neutralizing agents, we engineered Vβ mutants with high affinity for the superantigens staphylococcal enterotoxin B (SEB), SEC3, and streptococcal pyrogenic exotoxin A (SpeA). Unexpectedly, the high-affinity Vβ mutants generated against SEB cross-reacted with SpeA to a greater extent than they did with SEC3, despite greater sequence similarity between SEB and SEC3. Likewise, the Vβ mutants generated against SpeA cross-reacted with SEB to a greater extent than with SEC3. The structural basis of the high affinity and cross-reactivity was examined by single-site mutational analyses. The cross-reactivity seems to involve only one or two toxin residues. Soluble forms of the cross-reactive Vβ regions neutralized both SEB and SpeAin vivo, suggesting structure-based strategies for generating high-affinity neutralizing agents that can cross-react with multiple exotoxins.
Nested PCR-Linked Capillary Electrophoresis and Single-Strand Conformation Polymorphisms for Detection of Macrolide-Resistant
Mycoplasma pneumoniae
in Beijing, China
Authors: Lin Changying , Li Shaoli , Sun Hongmei , Zhao Hanqing , Feng Yanling , Cao Ling , Yuan Yi , Zhang Ting 
Published: September 2010

ABSTRACT

Mycoplasma pneumoniae
is usually susceptible to macrolides, but macrolide-resistant strains have been found frequently in recent years. Mutations in domain V of the 23S rRNA gene of
M. pneumoniae
interfere with the binding of macrolides to rRNA and mediate macrolide resistance. In this study, we developed a rapid and inexpensive method that combines nested PCR (nPCR), single-strand conformation polymorphisms (SSCPs), and capillary electrophoresis (CE) to detect macrolide-resistant mutants directly from throat swabs. nPCR was used to specifically amplify
M. pneumoniae
23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations, with results confirmed by sequencing. From January to December 2009, 665 throat swabs were collected in Beijing, China, yielding 110 samples that tested positive for
M. pneumoniae
by nPCR and serological testing. We randomly selected 64 positive throat swabs for CE-SSCP analysis. The A2063G mutation was found in 57 samples, and a coexisting T2611C mutation was identified in 1 sample. An A2063T mutation was identified in 1 sample. The total mutation rate was 91%. All mutant samples identified by nPCR-CE-SSCP were sequenced. The nPCR-CE-SSCP method could identify macrolide-resistant mutants directly from clinical samples. This is the first report of an nPCR-CE-SSCP assay for the detection of dominant mutations that confer macrolide resistance on
M. pneumoniae
. This approach would allow clinicians to choose appropriate therapy rapidly and could be used as a screening method for genetic mutations related to antibiotic resistance.
Improved Detection of Five Major Gastrointestinal Pathogens by Use of a Molecular Screening Approach
Authors: de Boer Richard F. , Ott Alewijn , Kesztyüs Barbara , Kooistra-Smid Anna M. D. 
Published: September 2010

ABSTRACT

The detection of bacterial and parasitic gastrointestinal pathogens through culture and microscopy is laborious and time-consuming. We evaluated a molecular screening approach (MSA) for the detection of five major enteric pathogens:
Salmonella enterica
,
Campylobacter jejuni
,
Giardia lamblia
, Shiga toxin-producing
Escherichia coli
(STEC), and
Shigella
spp./enteroinvasive
E. coli
(EIEC), for use in the daily practice of a clinical microbiology laboratory. The MSA consists of prescreening of stool specimens with two real-time multiplex PCR (mPCR) assays, which give results within a single working day, followed by guided culture/microscopy of the positive or mPCR-inhibited samples. In the present 2-year overview, 28,185 stool specimens were included. The MSA was applied to 13,974 stool samples (49.6%), whereas 14,211 samples were tested by conventional methods only (50.4%). The MSA significantly increased the total detection rate compared to that of conventional methods (19.2% versus 6.4%). The detection of all included pathogens, with the exception of
S. enterica
, significantly improved. MSA detection frequencies were as follows:
C. jejuni
, 8.1%;
G. lamblia
, 4.7%;
S. enterica
, 3.0%; STEC, 1.9%; and
Shigella
spp./EIEC, 1.4%. The guided culture/microscopy was positive in 76.8%, 58.1%, 88.9%, 16.8%, and 18.1% of mPCR-positive specimens, respectively. Of all mPCRs, only 1.8% was inhibited. Other findings were that detection of mixed infections was increased (0.9% versus 0.02%) and threshold cycle (

C
T

) values for MSA guided culture/microscopy-positive samples were significantly lower than those for guided culture/microscopy-negative samples. In conclusion, an MSA for detection of gastrointestinal pathogens resulted in markedly improved detection rates and a substantial decrease in time to reporting of (preliminary) results.
Rhino-Orbitocerebral Zygomycosis Caused by
Conidiobolus incongruus
in an Immunocompromised Patient in Germany
Authors: Wüppenhorst Nicole , Lee Mi-Kyung , Rappold Elfriede , Kayser Gian , Beckervordersandforth Jan , de With Katja , Serr Annerose 
Published: September 2010

ABSTRACT

Mucorales
(subphylum
Mucoromycotina
) are well-known agents of invasive mucormycosis, whereas
Entomophthorales
(subphylum
Entomophthoromycotina
) are rarely encountered in human diseases in temperate zones. Here we report a fatal case of invasive rhino-orbitocerebral entomophthoramycosis caused by
Conidiobolus incongruus
in a 78-year-old woman with myelodysplastic syndrome.
Performance of Genotypic Algorithms for Predicting HIV-1 Tropism Measured against the Enhanced-Sensitivity Trofile Coreceptor Tropism Assay
Authors: Sánchez Victoria , Masiá Mar , Robledano Catalina , Padilla Sergio , Ramos José Manuel , Gutiérrez Félix 
Published: September 2010

ABSTRACT

The objectives of this study were to assess the performance of genotypic algorithms for predicting CXCR4-using virus, with enhanced sensitivity Trofile HIV coreceptor tropism assay (ES Trofile) as the reference, and to compare the concordance/accuracy of genotypic tests with ES Trofile and with the original Trofile assay. Paired phenotypic and genotypic determinations of HIV-1 coreceptor usage were compared in plasma samples from HIV-1-infected patients. Sequencing of the third hypervariable (V3) loop of the viral gene and phenotypic assays were performed for each sample. Genotypic rules used to predict tropism were Geno2pheno (false-positive rate at 1 to 20%), position-specific scoring matrix X4R5 (PSSM
X4R5
) and PSSM
sinsi
(where “sinsi” stands for syncytium inducing and non-syncytium inducing), and the 11/25, 11/24/25, and net charge rules. Two hundred forty-four phenotypic and genotypic samples were tested. Coreceptor usage was obtained from ES Trofile for 145 (59%) samples and from Trofile for 99 (41%) samples. The highest concordance (82.6%) was obtained with PSSM
X4R5
when ES Trofile was used as the reference. Geno2pheno at a 20% false-positive rate showed the highest sensitivity (76.7%) for CXCR4-using virus detection with ES Trofile. Samples from naïve subjects and those with CD4 cell counts between 200 and 500 cells/mm
3
showed the best predictive performance. Overall, the accuracy of the bioinformatics tools to detect CXCR4-using virus was similar for ES Trofile and Trofile; however, the negative predictive values for genotypic tools with ES Trofile were slightly higher than they were with Trofile. The accuracy of genotypic algorithms for detecting CXCR4-using viruses is high when using ES Trofile as the reference. Results are similar to those obtained with Trofile. The concordance with ES Trofile is better with higher CD4 cell counts and nonexposure to antiretroviral therapy.
Evolution and Phylogeography of the Nonpathogenic Calicivirus RCV-A1 in Wild Rabbits in Australia
Authors: Jahnke Marlene , Holmes Edward C. , Kerr Peter J. , Wright John D. , Strive Tanja 
Published: September 2010

ABSTRACTDespite its potential importance for the biological control of European rabbits, relatively little is known about the evolution and molecular epidemiology of rabbit calicivirus Australia 1 (RCV-A1). To address this issue we undertook an extensive evolutionary analysis of 36 RCV-A1 samples collected from wild rabbit populations in southeast Australia between 2007 and 2009. Based on phylogenetic analysis of the entire capsid sequence, six clades of RCV-A1 were defined, each exhibiting strong population subdivision. Strikingly, our estimates of the time to the most recent common ancestor of RCV-A1 coincide with the introduction of rabbits to Australia in the mid-19th century. Subsequent divergence events visible in the RCV-A1 phylogenies likely reflect key moments in the history of the European rabbit in Australia, most notably the bottlenecks in rabbit populations induced by the two viral biocontrol agents used on the Australian continent, myxoma virus and rabbit hemorrhagic disease virus (RHDV). RCV-A1 strains therefore exhibit strong phylogeographic separation and may constitute a useful tool to study recent host population dynamics and migration patterns, which in turn could be used to monitor rabbit control in Australia.
Influenza A Virus Replication Induces Cell Cycle Arrest in G
0
/G
1
Phase
Authors: He Yuan , Xu Ke , Keiner Bjoern , Zhou Jianfang , Czudai Volker , Li Tianxian , Chen Ze , Liu Jinhua , Klenk Hans-Dieter , Shu Yue Long , Sun Bing 
Published: September 2010

ABSTRACT

Many viruses interact with the host cell division cycle to favor their own growth. In this study, we examined the ability of influenza A virus to manipulate cell cycle progression. Our results show that influenza A virus A/WSN/33 (H1N1) replication results in G
0
/G
1
-phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from G
0
/G
1
phase into S phase. Consistent with the G
0
/G
1
-phase accumulation, the amount of hyperphosphorylated retinoblastoma protein, a necessary active form for cell cycle progression through late G
1
into S phase, decreased after infection with A/WSN/33 (H1N1) virus. In addition, other key molecules in the regulation of the cell cycle, such as p21, cyclin E, and cyclin D1, were also changed and showed a pattern of G
0
/G
1
-phase cell cycle arrest. It is interesting that increased viral protein expression and progeny virus production in cells synchronized in the G
0
/G
1
phase were observed compared to those in either unsynchronized cells or cells synchronized in the G
2
/M phase. G
0
/G
1
-phase cell cycle arrest is likely a common strategy, since the effect was also observed in other strains, such as H3N2, H9N2, PR8 H1N1, and pandemic swine H1N1 viruses. These findings, in all, suggest that influenza A virus may provide favorable conditions for viral protein accumulation and virus production by inducing a G
0
/G
1
-phase cell cycle arrest in infected cells.
BST-2 Diminishes HIV-1 Infectivity
Authors: Zhang Jianyong , Liang Chen 
Published: September 2010

ABSTRACT
Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin/CD317/HM1.24) inhibits the release of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses by tethering virus particles to the cell surface. In this study, we provide evidence not only that the yield of cell-free HIV-1 particles is significantly reduced by BST-2 but also that the infectivity of these progeny virions is severely impaired. The lowered virion infectivity is due to the accumulation of pr55 Gag precursor and the p40Gag intermediates as well as to the loss of a mature core in the majority of HIV-1 particles. These data suggest that, in addition to impeding the release of HIV-1 particles from host cells, BST-2 may also interfere with the activation of viral protease and, as a result, impairs viral Gag processing as well as maturation of HIV-1 particles.
Cellular Immediate-Early Gene Expression Occurs Kinetically Upstream of Epstein-Barr Virus
bzlf1
and
brlf1
following Cross-Linking of the B Cell Antigen Receptor in the Akata Burkitt Lymphoma Cell Line
Authors: Ye Jianjiang , Gradoville Lyndle , Miller George 
Published: September 2010

ABSTRACT

The Epstein-Barr virus (EBV) lytic activator genes
bzlf1
and
brlf1
are conventionally referred to as immediate-early (IE) genes. However, previous studies showed that the earliest expression of these genes was blocked by cycloheximide when the EBV lytic cycle was induced by histone deacetylase (HDAC) inhibitors and protein kinase C agonists. Anti-IgG activates a complex signal transduction pathway that leads to EBV lytic activation in the Akata cell line. Here we demonstrate that in Akata cells, where lytic cycle activation occurs very rapidly after anti-IgG treatment,
de novo
protein synthesis is also required for induction of
bzlf1
and
brlf1
expression. New protein synthesis is required up to 1.25 h after application of anti-IgG;
bzlf1
and
brlf1
mRNAs can be detected 1.5 h after anti-IgG. Five cellular IE genes were shown to be expressed by 1 h after addition of anti-IgG, and their expression preceded that of
bzlf1
and
brlf1
. These include early growth response genes (
egr1
,
egr2
, and
egr3
) and nuclear orphan receptors (
nr4a1
and
nr4a3
). These genes were activated by anti-IgG treatment of Akata cells with and without the EBV genome; therefore, their expression was not dependent on expression of any EBV gene product. EGR1, EGR2, and EGR3 proteins were kinetically upstream of ZEBRA and Rta proteins. Expression of EGR1, ZEBRA, and Rta proteins were inhibited by bisindolylmaleimide X, a selective inhibitor of PKC. The findings suggest a revised model in which the signal transduction cascade activated by cross-linking of the B cell receptor induces expression of cellular IE genes, such as early growth response and nuclear orphan receptor genes, whose products, in turn, regulate
bzlf1
and
brlf1
expression.
Coxsackievirus Infection Induces Autophagy-Like Vesicles and Megaphagosomes in Pancreatic Acinar Cells
In Vivo
Authors: Kemball Christopher C. , Alirezaei Mehrdad , Flynn Claudia T. , Wood Malcolm R. , Harkins Stephanie , Kiosses William B. , Whitton J. Lindsay 
Published: September 2010

ABSTRACT

Autophagy can play an important part in protecting host cells during virus infection, and several viruses have developed strategies by which to evade or even exploit this homeostatic pathway. Tissue culture studies have shown that poliovirus, an enterovirus, modulates autophagy. Herein, we report on
in vivo
studies that evaluate the effects on autophagy of coxsackievirus B3 (CVB3). We show that in pancreatic acinar cells, CVB3 induces the formation of abundant small autophagy-like vesicles and permits amphisome formation. However, the virus markedly, albeit incompletely, limits the fusion of autophagosomes (and/or amphisomes) with lysosomes, and, perhaps as a result, very large autophagy-related structures are formed within infected cells; we term these structures megaphagosomes. Ultrastructural analyses confirmed that double-membraned autophagy-like vesicles were present in infected pancreatic tissue and that the megaphagosomes were related to the autophagy pathway; they also revealed a highly organized lattice, the individual components of which are of a size consistent with CVB RNA polymerase; we suggest that this may represent a coxsackievirus replication complex. Thus, these
in vivo
studies demonstrate that CVB3 infection dramatically modifies autophagy in infected pancreatic acinar cells.