bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetanus Immunity among Women Aged 15 to 39 Years in Cambodia: a National Population-Based Serosurvey, 2012
Authors: Scobie Heather M. , Mao Bunsoth , Buth Sokhal , Wannemuehler Kathleen A. , Sørensen Charlotte , Kannarath Chheng , Jenks M. Harley , Moss Delynn M. , Priest Jeffrey W. , Soeung Sann Chan , Deming Michael S. , Lammie Patrick J. , Gregory Christopher J. 
Published: April 2016

ABSTRACT

To monitor progress toward maternal and neonatal tetanus elimination (MNTE) in Cambodia, we conducted a nationwide serosurvey of tetanus immunity in 2012. Multistage cluster sampling was used to select 2,154 women aged 15 to 39 years. Tetanus toxoid antibodies in serum samples were measured by gold-standard double-antigen enzyme-linked immunosorbent assay (DAE) and a novel multiplex bead assay (MBA). Antibody concentrations of ≥0.01 IU/ml by DAE or the equivalent for MBA were considered seroprotective. Estimated tetanus seroprotection was 88% (95% confidence interval [CI], 86 to 89%); 64% (95% CI, 61 to 67%) of women had antibody levels of ≥1.0 IU/ml. Seroprotection was significantly lower (
P
< 0.001) among women aged 15 to 19 years (63%) and 20 to 24 years (87%) than among those aged ≥25 years (96%), among nulliparous women than among parous women (71 versus 97%), and among those living in the western region than among those living in other regions (82 versus 89%). The MBA showed high sensitivity (99% [95% CI, 98 to 99%]) and specificity (92% [95% CI, 88 to 95%]) compared with DAE. Findings were compatible with MNTE in Cambodia (≥80% protection). Tetanus immunity gaps should be addressed through strengthened routine immunization and targeted vaccination campaigns. Incorporating tetanus testing in national serosurveys using MBAs, which can measure immunity to multiple pathogens simultaneously, may be beneficial for monitoring MNTE.
Performance of the New Version (v2.0) of the GenoType MTBDR
sl
Test for Detection of Resistance to Second-Line Drugs in Multidrug-Resistant Mycobacterium tuberculosis Complex Strains
Authors: Brossier Florence , Guindo David , Pham Anne , Reibel Florence , Sougakoff Wladimir , Veziris Nicolas , Aubry Alexandra 
Published: April 2016

ABSTRACT

Detecting resistance to fluoroquinolones (FQ) and second-line injectable drugs (amikacin [AMK], kanamycin [KAN], and capreomycin [CAP]) is crucial given the worldwide increase in the incidence of extensively drug-resistant tuberculosis (XDR-TB). A new version of the GenoType MTBDR
sl
test (v2.0) has been developed to improve the detection of resistance to FQ (involving
gyrA
and
gyrB
mutations) and to second-line injectable drugs (involving
rrs
and
eis
promoter mutations) in
Mycobacterium tuberculosis
. A collection of 127 multidrug-resistant (MDR)
M. tuberculosis
complex strains was tested using the first (v1) and second (v2.0) versions of the MTBDR
sl
test, as well as DNA sequencing. The specificities in resistance detection of v1 and v2.0 were similar throughout, whereas the levels of sensitivity of v2.0 were superior for FQ (94.8% versus 89.6%) and KAN (90.5% versus 59.5%) but similar for AMK (91.3%) and CAP (83.0%). The sensitivity and specificity of v2.0 were superior to those of v1 for the detection of pre-XDR strains (83.3% versus 75.0% and 88.6% versus 67.1%, respectively), whereas the sensitivity of v2.0 was superior to that of v1 only for the detection of XDR strains (83.0% versus 49.1%). In conclusion, MTBDR
sl
v2.0 is superior to MTBDR
sl
v1 and efficiently detects the most common mutations involved in resistance to FQ and aminoglycosides/CAP. However, due to mutations not recognized by v2.0 or to the presence of resistance mechanisms not yet characterized (particularly mechanisms related to monoresistance to aminoglycosides or CAP), the results for wild-type strains obtained with MTBDR
sl
v2.0 should be confirmed by further DNA sequencing and phenotypic drug susceptibility testing.
Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?
Authors: Abras Alba , Gállego Montserrat , Llovet Teresa , Tebar Silvia , Herrero Mercedes , Berenguer Pere , Ballart Cristina , Martí Carmen , Muñoz Carmen 
Published: April 2016

ABSTRACT

Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity with
Leishmania
spp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity with
Leishmania
species. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.
In Vitro
Comparison of Ertapenem, Meropenem, and Imipenem against Isolates of Rapidly Growing Mycobacteria and Nocardia by Use of Broth Microdilution and Etest
Authors: Brown-Elliott Barbara A. , Killingley Jessica , Vasireddy Sruthi , Bridge Linda , Wallace Richard J. 
Published: April 2016

ABSTRACT

We compared the activities of the carbapenems ertapenem, meropenem, and imipenem against 180 isolates of rapidly growing mycobacteria (RGM) and 170 isolates of
Nocardia
using the Clinical and Laboratory Standards Institute (CLSI) guidelines. A subset of isolates was tested using the Etest. The rate of susceptibility to ertapenem and meropenem was limited and less than that to imipenem for the RGM. Analysis of major and minor discrepancies revealed that >90% of the isolates of
Nocardia
had higher MICs by the broth microdilution method than by Etest, in contrast to the lower broth microdilution MICs seen for >80% of the RGM. Imipenem remains the most active carbapenem against RGM, including
Mycobacterium abscessus
subsp.
abscessus
. For
Nocardia
, imipenem was significantly more active only against
Nocardia farcinica
. Although there may be utility in testing the activities of the newer carbapenems against
Nocardia
, their activities against the RGM should not be routinely tested. Testing by Etest is not recommended by the CLSI.
Evaluation of Multiple Methods for Detection of Gastrointestinal Colonization of Carbapenem-Resistant Organisms from Rectal Swabs
Authors: Simner Patricia J. , Martin Isabella , Opene Belita , Tamma Pranita D. , Carroll Karen C. , Milstone Aaron M. 
Published: April 2016

ABSTRACT

Rectal swabs from high-risk patients were screened for carbapenem-resistant organisms (CROs) using several methods. The direct MacConkey plate method was the most sensitive for CROs (95%), while chromID CARBA and the Check-Direct CPE screen assay were the most sensitive for the detection of carbapenemase-producing organisms (CPOs) (100%; all
bla
KPC
). All methods had a specificity of >90% for CROs, and for CPOs, the specificity ranged from 85 to 98%. Broth enrichment methods performed poorly compared to direct inoculation methods, negating the need for the broth enrichment step.
Defining the Clinical Significance of Alloscardovia omnincolens in the Urinary Tract
Authors: Brown Melanie K. , Forbes Betty A. , Stitley Kristin , Doern Christopher D. 
Published: April 2016

ABSTRACT

The clinical significance of
Alloscardovia omnincolens
in the urinary tract has not been thoroughly evaluated. In this study, 15 patients with
A. omnincolens
present in their urine cultures were identified.
A. omnincolens
is only rarely associated with urinary tract symptoms and in some patients may play a commensal role.
Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses
Authors: Yang Hua , Carney Paul J. , Mishin Vasiliy P. , Guo Zhu , Chang Jessie C. , Wentworth David E. , Gubareva Larisa V. , Stevens James 
Published: April 2016

ABSTRACT
During 2014, a subclade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around the world. In late 2014/early 2015, the virus was detected in wild birds in Canada and the United States, and these viruses also gave rise to reassortant progeny, composed of viral RNA segments (vRNAs) from both Eurasian and North American lineages. In particular, viruses were found with N1, N2, and N8 neuraminidase vRNAs, and these are collectively referred to as H5Nx viruses. In the United States, more than 48 million domestic birds have been affected. Here we present a detailed structural and biochemical analysis of the surface antigens of H5N1, H5N2, and H5N8 viruses in addition to those of a recent human H5N6 virus. Our results with recombinant hemagglutinin reveal that these viruses have a strict avian receptor binding preference, while recombinantly expressed neuraminidases are sensitive to FDA-approved and investigational antivirals. Although H5Nx viruses currently pose a low risk to humans, it is important to maintain surveillance of these circulating viruses and to continually assess future changes that may increase their pandemic potential.

IMPORTANCE
The H5Nx viruses emerging in North America, Europe, and Asia pose a great public health concern. Here we report a molecular and structural study of the major surface proteins of several H5Nx influenza viruses. Our results improve the understanding of these new viruses and provide important information on their receptor preferences and susceptibilities to antivirals, which are central to pandemic risk assessment.
Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine
Authors: Kristensen Anne B. , Lay William N. , Ana-Sosa-Batiz Fernanda , Vanderven Hillary A. , Madhavi Vijaya , Laurie Karen L. , Carolan Louise , Wines Bruce D. , Hogarth Mark , Wheatley Adam K. , Kent Stephen J. 
Published: April 2016

ABSTRACT
This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV-positive group had detectable but reduced functional Ab responses to both vaccine and nonvaccine influenza antigens. TIV enhanced Fc-mediated Ab responses in both HIV-positive and HIV-negative groups. A larger rise was generally observed in the HIV-positive group, such that there was no difference in functional Ab responses between the two groups after vaccination. The 2015 TIV enhanced functional influenza-specific Ab responses in both HIV-negative and HIV-positive subjects to a range of influenza HA proteins. The increase in functional Ab responses in the HIV-positive group supports recommendations to immunize this at-risk group.

IMPORTANCE
Infection with HIV is associated with increasing disease severity following influenza infections, and annual influenza vaccinations are recommended for this target group. However, HIV-infected individuals respond relatively poorly to vaccination compared to healthy individuals, particularly if immunodeficient. There is therefore a need to increase our understanding of immunity to influenza in the context of underlying HIV infection. While antibodies can mediate direct virus neutralization, interactions with cellular Fc receptors may be important for anti-influenza immunity
in vivo
by facilitating antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent phagocytosis (ADP). The ability of seasonal influenza vaccines to induce antibody responses with potent Fc-mediated antiviral activity is currently unclear. Probing the ADCC and ADP responses to influenza vaccination has provided important new information in the quest to improve immunity to influenza.
Transmembrane Domains of NS2B Contribute to both Viral RNA Replication and Particle Formation in Japanese Encephalitis Virus
Authors: Li Xiao-Dan , Deng Cheng-Lin , Ye Han-Qing , Zhang Hong-Lei , Zhang Qiu-Yan , Chen Dong-Dong , Zhang Pan-Tao , Shi Pei-Yong , Yuan Zhi-Ming , Zhang Bo 
Published: April 2016

ABSTRACT
Flavivirus nonstructural protein 2B (NS2B) is a transmembrane protein that functions as a cofactor for viral NS3 protease. The cytoplasmic region (amino acids 51 to 95) alone of NS2B is sufficient for NS3 protease activity, whereas the role of transmembrane domains (TMDs) remains obscure. Here, we demonstrate for the first time that flavivirus NS2B plays a critical role in virion assembly. Using Japanese encephalitis virus (JEV) as a model, we performed a systematic mutagenesis at the flavivirus conserved residues within the TMDs of NS2B. As expected, some mutations severely attenuated (L38A and R101A) or completely destroyed (G12L) viral RNA synthesis. Interestingly, two mutations (G37L and P112A) reduced viral RNA synthesis and blocked virion assembly. None of the mutations affected NS2B-NS3 protease activity. Because mutations G37L and P112A affected virion assembly, we selected revertant viruses for these two mutants. For mutant G37L, replacement with G37F, G37H, G37T, or G37S restored virion assembly. For mutant P112A, insertion of K at position K127 (leading to K127KK) of NS2B rescued virion assembly. A biomolecular fluorescent complementation (BiFC) analysis demonstrated that (i) mutation P112A selectively weakened NS2B-NS2A interaction and (ii) the adaptive mutation K127KK restored NS2B-NS2A interaction. Collectively, our results demonstrate that, in addition to being a cofactor for NS3 protease, flavivirus NS2B also functions in viral RNA replication, as well as virion assembly.

IMPORTANCE
Many flaviviruses are important human pathogens. Understanding the molecular mechanisms of the viral infection cycle is essential for vaccine and antiviral development. In this study, we demonstrate that the TMDs of JEV NS2B participate in both viral RNA replication and virion assembly. A viral genetic study and a BiFC assay demonstrated that interaction between NS2B and NS2A may participate in modulating viral assembly in the flavivirus life cycle. Compensatory-mutation analysis confirmed that there was a correlation between viral assembly and NS2B-NS2A interaction. TMDs of NS2B may serve as novel antiviral targets to prevent flavivirus infection, and the structure determination of NS2B will help us to understand the functional mechanism of NS2B in viral RNA replication and assembly. The results have uncovered a new function of flavivirus NS2B in virion assembly, possibly through interaction with the NS2A protein.
Intracellular Distribution of Capsid-Associated pUL77 of Human Cytomegalovirus and Interactions with Packaging Proteins and pUL93
Authors: Köppen-Rung Pánja , Dittmer Alexandra , Bogner Elke 
Published: April 2016

ABSTRACT
DNA packaging into procapsids is a common multistep process during viral maturation in herpesviruses. In human cytomegalovirus (HCMV), the proteins involved in this process are terminase subunits pUL56 and pUL89, which are responsible for site-specific cleavage and insertion of the DNA into the procapsid via portal protein pUL104. However, additional viral proteins are required for the DNA packaging process. We have shown previously that the plasmid that encodes capsid-associated pUL77 encodes another potential player during capsid maturation. Pulse-chase experiments revealed that pUL77 is stably expressed during HCMV infection. Time course analysis demonstrated that pUL77 is expressed in the early late part of the infectious cycle. The sequence of pUL77 was analyzed to find nuclear localization sequences (NLSs), revealing monopartite NLSm at the N terminus and bipartite NLSb in the middle of pUL77. The potential NLSs were inserted into plasmid pHM829, which encodes a chimeric protein with β-galactosidase and green fluorescent protein. In contrast to pUL56, neither NLSm nor NLSb was sufficient for nuclear import. Furthermore, we investigated by coimmunoprecipitation whether packaging proteins, as well as pUL93, the homologue protein of herpes simplex virus 1 pUL17, are interaction partners of pUL77. The interactions between pUL77 and packaging proteins, as well as pUL93, were verified.

IMPORTANCE
We showed that the capsid-associated pUL77 is another potential player during capsid maturation of HCMV. Protein UL77 (pUL77) is a conserved core protein of HCMV. This study demonstrates for the first time that pUL77 has early-late expression kinetics during the infectious cycle and an intrinsic potential for nuclear translocation. According to its proposed functions in stabilization of the capsid and anchoring of the encapsidated DNA during packaging, interaction with further DNA packaging proteins is required. We identified physical interactions with terminase subunits pUL56 and pUL89 and another postulated packaging protein, pUL93, in infected, as well as transfected, cells.
Commandeering the Ribosome: Lessons Learned from Dicistroviruses about Translation
Authors: Kerr Craig H. , Jan Eric 
Published: April 2016

ABSTRACT

To replicate, all viruses depend entirely on the enslavement of host cell ribosomes for their own advantage. To this end, viruses have evolved a multitude of translational strategies to usurp the ribosome. RNA-based structures known as internal ribosome entry sites (IRESs) are among the most notable mechanisms employed by viruses to seize host ribosomes. In this article, we spotlight the intergenic region IRES from the
Dicistroviridae
family of viruses and its importance as a model for IRES-dependent translation and in understanding fundamental properties of translation.
Entry Sites of Venezuelan and Western Equine Encephalitis Viruses in the Mouse Central Nervous System following Peripheral Infection
Authors: Phillips Aaron T. , Rico Amber B. , Stauft Charles B. , Hammond Sean L. , Aboellail Tawfik A. , Tjalkens Ronald B. , Olson Ken E. 
Published: April 2016

ABSTRACT

Venezuelan and western equine encephalitis viruses (VEEV and WEEV;
Alphavirus
;
Togaviridae
) are mosquito-borne pathogens causing central nervous system (CNS) disease in humans and equids. Adult CD-1 mice also develop CNS disease after infection with VEEV and WEEV. Adult CD-1 mice infected by the intranasal (i.n.) route, showed that VEEV and WEEV enter the brain through olfactory sensory neurons (OSNs). In this study, we injected the mouse footpad with recombinant WEEV (McMillan) or VEEV (subtype IC strain 3908) expressing firefly luciferase (fLUC) to simulate mosquito infection and examined alphavirus entry in the CNS. Luciferase expression served as a marker of infection detected as bioluminescence (BLM) by
in vivo
and
ex vivo
imaging. BLM imaging detected WEEV and VEEV at 12 h postinoculation (hpi) at the injection site (footpad) and as early as 72 hpi in the brain. BLM from WEEV.McM-fLUC and VEEV.3908-fLUC injections was initially detected in the brain's circumventricular organs (CVOs). No BLM activity was detected in the olfactory neuroepithelium or OSNs. Mice were also injected in the footpad with WEEV.McM expressing DsRed (
Discosoma
sp.) and imaged by confocal fluorescence microscopy. DsRed imaging supported our BLM findings by detecting WEEV in the CVOs prior to spreading along the neuronal axis to other brain regions. Taken together, these findings support our hypothesis that peripherally injected alphaviruses enter the CNS by hematogenous seeding of the CVOs followed by centripetal spread along the neuronal axis.

IMPORTANCE
VEEV and WEEV are mosquito-borne viruses causing sporadic epidemics in the Americas. Both viruses are associated with CNS disease in horses, humans, and mouse infection models. In this study, we injected VEEV or WEEV, engineered to express bioluminescent or fluorescent reporters (fLUC and DsRed, respectively), into the footpads of outbred CD-1 mice to simulate transmission by a mosquito. Reporter expression serves as detectable bioluminescent and fluorescent markers of VEEV and WEEV replication and infection. Bioluminescence imaging, histological examination, and confocal fluorescence microscopy were used to identify early entry sites of these alphaviruses in the CNS. We observed that specific areas of the brain (circumventricular organs [CVOs]) consistently showed the earliest signs of infection with VEEV and WEEV. Histological examination supported VEEV and WEEV entering the brain of mice at specific sites where the blood-brain barrier is naturally absent.
Drugs to treat obesity: do they work?
Authors: Kim Sarah 
Published: April 2016

AbstractObesity is a disease that has historically eluded effective medical therapy. Prior to 2012, phentermine and orlistat were the only medications available to treat obesity in the USA, with phentermine approved only for short-term use. However, as of 2015, the repertoire of pharmacological agents available to treat obesity has greatly expanded to include four new drugs: lorcaserin, phentermine/topiramate extended release (ER), naltrexone ER/wellbutrin ER and liraglutide. Each has a unique mechanism of action and all are intended for long-term use. These newer medications share a common strategy to promote weight loss in that they are designed to manipulate the control of hunger and satiety in the central nervous system. Interestingly, the majority of these new agents are combinations of older medications that have been used for conditions other than obesity. The amount of weight loss seen with these agents beyond placebo varies but generally falls in the range of 3–10% of starting weight and requires continual use of the drug in order for weight loss to be sustained. In addition, each drug has a unique side effect profile that should be carefully considered when selecting the best agent for a given individual. This article provides a review of these recently approved medications focusing on efficacy, side effect profiles and appropriate application to the individual patient.