bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Molecular Characteristics of Invasive and Noninvasive Skin and Soft Tissue Infections Caused by Group A Streptococcus
Authors: Lin Jiun-Nong , Chang Lin-Li , Lai Chung-Hsu , Lin Hsi-Hsun , Chen Yen-Hsu 
Published: August 2011

ABSTRACT

The severity of skin and soft tissue infections caused by group A
Streptococcus
(GAS) is variable, and there are only a limited number of studies evaluating the characteristics of these infections in the literature. From May 2005 to November 2007, 73 patients with skin and soft tissue infections caused by group A
Streptococcus
were included in this study. Among these patients, 34 (46.6%) had invasive diseases. Diabetes mellitus, alcoholism, and hypertension were the most common underlying disorders. The overall mortality rate was 6.8%, and the elderly were predisposed to invasive infections (
P
< 0.001). Neutrophil percentages of ≥80, serum creatinine levels of ≥2 mg/dl, and high serum C-reactive protein levels were noted more frequently in patients with invasive infections than in patients with noninvasive infections, as were bacteremia and a high mortality rate. Of the 73 isolates, 93.2%, 97.3%, and 37% exhibited susceptibility to erythromycin, clindamycin, and tetracycline, respectively. The five most prevalent
emm
types were
emm
106 (24.7%),
emm
11 (12.3%),
emm
102 (9.6%),
emm
4 (8.2%), and
emm
12 (8.2%). Compared to other types, the
emm
106 type was significantly more likely to be associated with invasive diseases (
P
= 0.012). Dendrogram analysis showed a unique SmaI-digested pulsed-field gel electrophoresis pattern of the
emm
106 type that was particularly prone to cause invasive skin and soft tissue infections (
P
< 0.001). The results of this study suggest that isolates with the
emm
106 gene may be an emerging group A
Streptococcus
strain that causes invasive skin and soft tissue infections. Further surveillance study to understand the significance of this invasive strain is critical.
Visual Detection of High-Risk Human Papillomavirus Genotypes 16, 18, 45, 52, and 58 by Loop-Mediated Isothermal Amplification with Hydroxynaphthol Blue Dye
Authors: Luo Le , Nie Kai , Yang Meng-Jie , Wang Miao , Li Jin , Zhang Chen , Liu Hong-Tu , Ma Xue-Jun 
Published: August 2011

ABSTRACT
A simple, rapid, sensitive, qualitative, colorimetric loop-mediated isothermal amplification (LAMP) with hydroxynaphthol blue dye (HNB) was established to detect high-risk human papillomavirus (HPV) genotypes 16, 18, 45, 52, and 58. All initial validation studies with the control DNA proved to be type specific. The colorimetric type-specific LAMP assay could achieve a sensitivity of 10 to 100 copies at 63°C for 65 min, comparable to that of real-time PCR. In order to evaluate the reliability of HPV type-specific LAMP, the assay was further evaluated with HPV DNAs from a panel of 294 clinical specimens whose HPV status was previously determined with a novel one-step typing method with multiplex PCR. The tested panel comprised 108 HPV DNA-negative samples and 186 HPV-DNA-positive samples of 14 genotypes. The results showed that the sensitivity of HPV type-specific LAMP for HPV types 16, 18, 45, 52, and 58 was 100%, 100%, 100%, 100%, and 100%, respectively, and the specificity was 100%, 98.5%, 100%, 98.8%, and 99.2%, respectively, compared with a novel one-step typing method with multiplex PCR. No cross-reactivity with other HPV genotypes was observed. In conclusion, this qualitative and colorimetric LAMP assay has potential usefulness for the rapid screening of HPV genotype 16, 18, 45, 52, and 58 infections, especially in resource-limited hospitals or rural clinics of provincial and municipal regions in China.
Predictors of Relapse of Methicillin-Resistant Staphylococcus aureus Bacteremia after Treatment with Vancomycin
Authors: Welsh Kerry J. , Skrobarcek Kimberly A. , Abbott April N. , Lewis Cole T. , Kruzel Mark C. , Lewis Evan M. , Gardiner Jeanelle M. , Mohr John F. , Armitige Lisa Y. , Wanger Audrey 
Published: August 2011

ABSTRACT

The risk factors for relapse of methicillin-resistant
Staphylococcus aureus
(MRSA) bacteremia after vancomycin treatment are unknown. Diversilab typing was used to classify recurrent bacteremia as relapse or reinfection. Bacteremia for >7 days and staphylococcal cassette chromosome
mec
element (SCC
mec
) type II were independently associated with relapse of MRSA bacteremia after vancomycin treatment.
MyD88 Plays an Essential Role in Inducing B Cells Capable of Differentiating into Antibody-Secreting Cells after Vaccination
Authors: Kang Sang-Moo , Yoo Dae-Goon , Kim Min-Chul , Song Jae-Min , Park Min-Kyung , O Eunju , Quan Fu-Shi , Akira Shizuo , Compans Richard W. 
Published: August 2011

ABSTRACTWe investigated the roles of MyD88, an innate adaptor signaling molecule, in inducing protective humoral immunity after vaccination with influenza virus-like particles (VLPs). MyD88 knockout C57BL/6 mice (MyD88−/−mice) vaccinated with influenza VLPs showed significant defects in inducing IgG2a/c isotype antibodies and in generating splenic recall memory B cell responses and antibody-secreting plasma cells in the bone marrow. The protective efficacy of influenza VLP vaccination was lower in MyD88−/−mice than in the wild-type mice. Our findings indicate that MyD88-mediated innate signaling pathways are important for effectively inducing primary and boost immune responses, T helper type 1 isotype-switched antibodies, and gamma interferon (IFN-γ)-secreting T cell responses. In particular, the results in this study demonstrated for the first time that MyD88-mediated immune activation is likely an essential pathway for effective generation of long-lived antibody-secreting plasma cells and highly protective immunity after vaccination with influenza VLPs. This study provides insight into mechanisms by which recombinant viral vaccines induce protective immunity via the MyD88-mediated innate immune signaling pathway.
Inhibition of Hepatitis B Virus Replication by cIAP2 Involves Accelerating the Ubiquitin-Proteasome-Mediated Destruction of Polymerase
Authors: Wang Zekun , Ni Jinjing , Li Jianhua , Shi Bisheng , Xu Yang , Yuan Zhenghong 
Published: August 2011

ABSTRACT
Cellular inhibitor of apoptosis protein 2 (cIAP2) is a potent suppressor of apoptotic cell death. We have shown previously that cIAP2 is involved in the tumor necrosis factor alpha (TNF-α)-induced anti-hepatitis B virus (HBV) response; however, the mechanism for this antiviral effect remains unclear. In the present study, we demonstrate that cIAP2 can significantly reduce the levels of HBV DNA replication intermediates but not the total viral RNA or core protein levels. Domain-mapping analysis revealed that the carboxy-terminal domains of cIAP2 were indispensable for this anti-HBV ability and that an E3 ligase-deficient mutant of cIAP2 (termed cIAP2*) completely lost its antiviral activity. We further identified HBV polymerase as the target of cIAP2. Overexpression of cIAP2 but not cIAP2* reduced polymerase protein levels, while cIAP2 knockdown increased polymerase expression. In addition, we observed that cIAP2 promoted the degradation of the viral polymerase through a proteasome-dependent pathway. Further experiments demonstrated that cIAP2 can bind to polymerase and promote its polyubiquitylation. Finally, we found that cIAP2 downregulated the encapsidation of HBV pregenomic RNA. Taken together, these data reveal a novel mechanism for the inhibition of HBV replication by cIAP2 via acceleration of the ubiquitin-proteasome-mediated decay of polymerase and reduction of the encapsidation of HBV pregenomic RNA, making this mechanism a novel strategy for HBV therapy.
Determinants of Bluetongue Virus Virulence in Murine Models of Disease
Authors: Caporale Marco , Wash Rachael , Pini Attilio , Savini Giovanni , Franchi Paola , Golder Matthew , Patterson-Kane Janet , Mertens Peter , Di Gialleonardo Luigina , Armillotta Gisella , Lelli Rossella , Kellam Paul , Palmarini Massimo 
Published: August 2011

ABSTRACTBluetongue is a major infectious disease of ruminants that is caused by bluetongue virus (BTV). In this study, we analyzed virulence and genetic differences of (i) three BTV field strains from Italy maintained at either a low (L strains) or high (H strains) passage number in cell culture and (ii) three South African “reference” wild-type strains and their corresponding live attenuated vaccine strains. The Italian BTV L strains, in general, were lethal for both newborn NIH-Swiss mice inoculated intracerebrally and adult type I interferon receptor-deficient (IFNAR−/−) mice, while the virulence of the H strains was attenuated significantly in both experimental models. Similarly, the South African vaccine strains were not pathogenic for IFNAR−/−mice, while the corresponding wild-type strains were virulent. Thus, attenuation of the virulence of the BTV strains used in this study is not mediated by the presence of an intact interferon system. No clear distinction in virulence was observed for the South African BTV strains in newborn NIH-Swiss mice. Full genomic sequencing revealed relatively few amino acid substitutions, scattered in several different viral proteins, for the strains found to be attenuated in mice compared to the pathogenic related strains. However, only the genome segments encoding VP1, VP2, and NS2 consistently showed nonsynonymous changes between all virulent and attenuated strain pairs. This study established an experimental platform for investigating the determinants of BTV virulence. Future studies using reverse genetics will allow researchers to precisely map and “weight” the relative influences of the various genome segments and viral proteins on BTV virulence.
H5N1 Virus-Like Particle Vaccine Elicits Cross-Reactive Neutralizing Antibodies That Preferentially Bind to the Oligomeric Form of Influenza Virus Hemagglutinin in Humans
Authors: Khurana Surender , Wu Jian , Verma Nitin , Verma Swati , Raghunandan Ramadevi , Manischewitz Jody , King Lisa R. , Kpamegan Eloi , Pincus Steven , Smith Gale , Glenn Gregory , Golding Hana 
Published: August 2011

ABSTRACT
Transmission of pathogenic avian influenza viruses (AIV) from wild birds to domestic poultry and humans is continuing in multiple countries around the world. In preparation for a potential AIV pandemic, multiple vaccine candidates are under development. In the case of H5N1 AIV, a clear shift in transmission from clade 1 to clade 2 viruses occurred in recent years. The virus-like particle (VLP) represents an economical approach to pandemic vaccine development. In the current study, we evaluated the humoral immune response in humans vaccinated with H5N1 A/Indonesia/05/2005 (clade 2.1) VLP vaccine manufactured in Sf9 insect cells. The VLPs were comprised of the influenza virus hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1) proteins. In an FDA-approved phase I/II human clinical study, two doses of H5N1 VLPs at 15, 45, or 90 μg HA/dose resulted in seroconversion and production of functional antibodies. Moreover, cross-reactivity against other clade 2 subtypes was demonstrated using virus neutralization assays. H5N1 whole-genome fragment phage display libraries (GFPDL) were used to elucidate the antibody epitope repertoire in postvaccination human sera. Diverse epitopes in HA1/HA2 and NA were recognized by postvaccination sera from the two high-dose groups, including large segments spanning the HA1 receptor binding domain. Importantly, the vaccine elicited sera that preferentially bound to an oligomeric form of recombinant HA1 compared with monomeric HA1. The oligomeric/monomeric HA1 binding ratios of the sera correlated with the virus neutralizing titers. Additionally, the two high-dose VLP vaccine groups generated NA-inhibiting antibodies that were associated with binding to a C-terminal epitope close to the sialic acid binding site. These findings represent the first report describing the quality of the antibody responses in humans following AIV VLP immunization and support further development of such vaccines against emerging influenza virus strains.
A Duck Enteritis Virus-Vectored Bivalent Live Vaccine Provides Fast and Complete Protection against H5N1 Avian Influenza Virus Infection in Ducks
Authors: Liu Jinxiong , Chen Pucheng , Jiang Yongping , Wu Li , Zeng Xianying , Tian Guobin , Ge Jinying , Kawaoka Yoshihiro , Bu Zhigao , Chen Hualan 
Published: August 2011

ABSTRACT

Ducks play an important role in the maintenance of highly pathogenic H5N1 avian influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks has important implications for the eradication of the disease in poultry and its prevention in humans. The inactivated influenza vaccine is expensive, labor-intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks. Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used routinely to control lethal DEV infections in many duck-producing areas. Here, we first established a system to generate the DEV vaccine strain by using the transfection of overlapping fosmid DNAs. Using this system, we constructed two recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA) gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck studies indicated that rDEV-us78HA had protective efficacy similar to that of the live DEV vaccine against lethal DEV challenge; importantly, a single dose of 10
6
PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus challenge in as little as 3 days postvaccination. The protective efficacy against both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks was slightly weaker than that provided by rDEV-us78HA. These results demonstrate, for the first time, that recombinant DEV is suitable for use as a bivalent live attenuated vaccine, providing rapid protection against both DEV and H5N1 virus infection in ducks.
Inhibition of Dengue Virus by Targeting Viral NS4B Protein
Authors: Xie Xuping , Wang Qing-Yin , Xu Hao Ying , Qing Min , Kramer Laura , Yuan Zhiming , Shi Pei-Yong 
Published: August 2011

ABSTRACT

We report a novel inhibitor that selectively suppresses dengue virus (DENV) by targeting viral NS4B protein. The inhibitor was identified by screening a 1.8-million-compound library using a luciferase replicon of DENV serotype 2 (DENV-2). The compound specifically inhibits all four serotypes of DENV (50% effective concentration [EC
50
], 1 to 4 μM; and 50% cytotoxic concentration [CC
50
], >40 μM), but it does not inhibit closely related flaviviruses (West Nile virus and yellow fever virus) or nonflaviviruses (Western equine encephalomyelitis virus, Chikungunya virus, and vesicular stomatitis virus). A mode-of-action study suggested that the compound inhibits viral RNA synthesis. Replicons resistant to the inhibitor were selected in cell culture. Sequencing of the resistant replicons revealed two mutations (P104L and A119T) in the viral NS4B protein. Genetic analysis, using DENV-2 replicon and recombinant viruses, demonstrated that each of the two NS4B mutations alone confers partial resistance and double mutations confer additive resistance to the inhibitor in mammalian cells. In addition, we found that a replication defect caused by a lethal NS4B mutation could be partially rescued through
trans
complementation. The ability to complement NS4B in
trans
affected drug sensitivity when a single cell was coinfected with drug-sensitive and drug-resistant viruses. Mechanistically, NS4B was previously shown to interact with the viral NS3 helicase domain; one of the two NS4B mutations recovered in our resistance analysis—P104L—abolished the NS3-NS4B interaction (I. Umareddy, A. Chao, A. Sampath, F. Gu, and S. G. Vasudevan, J. Gen. Virol. 87:2605-2614, 2006). Collectively, the results suggest that the identified inhibitor targets the DENV NS4B protein, leading to a defect in viral RNA synthesis.
Improved Knockout Methodology Reveals That Frog Virus 3 Mutants Lacking either the
18K
Immediate-Early Gene or the Truncated
vIF-2
α Gene Are Defective for Replication and Growth
In Vivo
Authors: Chen Guangchun , Ward Brian M. , Yu Kwang H. , Chinchar V. Gregory , Robert Jacques 
Published: August 2011

ABSTRACT

To better assess the roles of frog virus 3 (FV3; genus
Ranavirus
, family
Iridoviridae
) genes in virulence and immune evasion, we have developed a reliable and efficient method to systematically knock out (KO) putative virulence genes by site-specific integration into the FV3 genome. Our approach utilizes a dual selection marker consisting of the puromycin resistance gene fused in frame with the enhanced green fluorescent protein (EGFP) reporter (Puro-EGFP cassette) under the control of the FV3 immediate-early (IE)
18K
promoter. By successive rounds of selection for puromycin resistance and GFP expression, we have successfully constructed three recombinant viruses. In one, a “knock-in” mutant was created by inserting the Puro-EGFP cassette into a noncoding region of the FV3 genome (FV3-Puro/GFP). In the remaining two, KO mutants were constructed by replacement of the truncated viral homolog of
eIF-2α
(FV3-ΔvIF-2α) or the
18K
IE gene (FV3-Δ18K) with the Puro-EGFP cassette. The specificity of recombination and the clonality of each mutant were confirmed by PCR, sequencing, and immunofluorescence microscopy. Viral replication of each recombinant in cell culture was similar to that of parental FV3; however, infection in
Xenopus laevis
tadpoles revealed that FV3-ΔvIF-2α and FV3-Δ18K replicated less and resulted in lower mortality than did GFP-FV3 and wild-type FV3. Our results suggest that
18K
, which is conserved in all ranaviruses, and the truncated
vIF-2α
gene contribute to virulence. In addition, our study describes a powerful methodology that lays the foundation for the discovery of potentially new ranaviral genes involved in virulence and immune escape.
Impact of integrating a physical activity counsellor into the primary health care team: physical activity and health outcomes of the Physical Activity Counselling randomized controlled trial
Authors: Fortier Michelle S. , Hogg William , O’Sullivan Tracey L. , Blanchard Christopher , Sigal Ronald J. , Reid Robert D. , Boulay Pierre , Doucet Éric , Bisson Étienne , Beaulac Julie , Culver Diane 
Published: August 2011

The purpose of this paper was to report the physical activity and health outcomes results from the Physical Activity Counselling (PAC) trial. Patients (n = 120, mean age 47.3 ± 11.1 years, 69.2% female) who reported less than 150 min of physical activity per week were recruited from a large community-based Canadian primary care practice. After receiving brief physical activity counselling from their provider, they were randomized to receive 6 additional patient-centered counselling sessions over 3 months from a physical activity counsellor (intensive-counselling group; n = 61), or no further intervention (brief-counselling group; n = 59). Physical activity (self-reported and accelerometer) was measured every 6 weeks up to 25 weeks (12 weeks postintervention). Quality of life was also assessed, and physical and metabolic outcomes were evaluated in a randomly selected subset of patients (33%). In the intent-to-treat analyses of covariance, the intensive-counselling group self-reported significantly higher levels of physical activity at 6 weeks (p = 0.009) and 13 weeks (p = 0.01). There were no differences in self-reported physical activity between the groups after the intervention in the follow-up period, nor was there any increase in accelerometer-measured physical activity. Finally, the intensive-counselling patients showed greater decreases in percent body fat and total fat mass from 13 weeks to 25 weeks. Results for physical activity depended on the method used, with positive short-term results with self-report and no effects with the accelerometers. Between-group differences were found for body composition in that the intensive-counselling patients decreased more. A multisite randomized controlled trial with a longer intensive intervention and follow-up is warranted.
Step-based translation of physical activity guidelines in the Lower Mississippi Delta
Authors: Harrington Deirdre M. , Tudor-Locke Catrine , Champagne Catherine M. , Broyles Stephanie T. , Harsha David W. , Kennedy Betty M. , Johnson William D. , Allen Ray , Katzmarzyk Peter T. 
Published: August 2011

To determine how many steps·day–1 equate to current moderate-to-vigorous physical activity (MVPA) guidelines in a population from the Lower Mississippi Delta (LMD) of the United States, 58 overweight adults wore an Actigraph accelerometer (GT3X) for up to 2 weeks. Min·day–1 in MVPA was a good predictor of steps·day–1 (r2 = 0.62; p < 0.001; linear regression), such that 30 min of daily MVPA equated to 9154 steps·day–1 (mixed-model approach). Using receiver operating characteristic analysis, sensitivity and specificity were optimized at 8357 steps·day–1. Results indicate that overweight residents of the LMD should be accumulating at least 8300–9100 steps·day–1 to meet the recommendation of 30 min·day–1 MVPA.
Benign multiple sclerosis: a new definition of this entity is needed
Authors: Correale Jorge , Peirano Isabel , Romano Lucas 
Published: August 2011

Background: To study a cohort of benign multiple sclerosis (BMS) patients beyond physical disability, including the evaluation of cognitive and social function, as well as fatigue, pain and MRI studies. Methods: A cohort of 342 patients was prospectively followed for 10.9 ± 0.71 years. Forty-three patients (12.5%) met the BMS diagnosis criteria [Expanded Disability Status Scale (EDSS) < 3 after at least 10 years’ disease duration], undergoing full neurological examination every 6 months. Neuropsychological status, pain, fatigue, social functioning and work-related disability, as well as brain MRIs, were assessed yearly. Results: By the end of follow-up, 20 of 43 BMS patients (47%) had suffered cognitive impairment and 23 (53.3%) referred depression. Furthermore, 21 (48.8%) reported significant changes in pain intensity, with fatigue and environmental severity scores significantly increasing over time in 33–35% of patients. Finally, 32 BMS patients (74%) showed significant increase in the number of new or enlarging T2 lesions, gadolinium-enhanced lesions, and persistent black holes, without changes in EDSS. Thirty-five of 43 patients (81%) fulfilling the BMS diagnostic criteria showed significant worsening of cognitive function, fatigue, pain or depression during the 10-year follow-up. Conclusions: Currently accepted criteria for BMS diagnosis may cause overestimation of true prevalence, underscoring the need for routine monitoring of non-motor symptoms and imaging studies, to help physicians improve diagnostic accuracy as well as therapeutic decision-making in this subgroup of MS patients.