bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Isolates of Salmonella enterica Serovar Agona Producing NDM-1 Metallo-β-Lactamase: First Report from Pakistan
Authors: Irfan Seema , Khan Erum , Jabeen Kauser , Bhawan Pushpa , Hopkins Katie L. , Day Martin , Nasir Amna , Meunier Daniele , Woodford Neil 
Published: November 2014

ABSTRACT

We report two cases of infantile diarrhea due to multidrug-resistant, NDM-1 metallo-β-lactamase-producing
Salmonella enterica
serovar Agona from Pakistan. This study alerts toward possible risk of NDM-1 transmission to enteric fever pathogens and encourages microbiologists to consider active screening of carbapenem resistance in nontyphoidal
Salmonella
isolates.
Laboratory Evaluation of a Dual Rapid Immunodiagnostic Test for HIV and Syphilis Infection
Authors: Bristow Claire C. , Leon Segundo R. , Ramos Lourdes B. , Vargas Silver K. , Flores Juan A. , Konda Kelika A. , Caceres Carlos F. , Klausner Jeffrey D. 
Published: November 2014

ABSTRACT
New dual tests for HIV and syphilis have been developed. Our study aimed to evaluate the laboratory performance of a dual rapid immunodiagnostic test for HIV and syphilis. Our evaluation showed high performance of this dual rapid test, which should be considered for implementation to increase screening coverage and efficiency.
Evidence of Lymphocytic Choriomeningitis Virus (LCMV) in Domestic Mice in Gabon: Risk of Emergence of LCMV Encephalitis in Central Africa
Authors: N′Dilimabaka Nadine , Berthet Nicolas , Rougeron Virginie , Mangombi Joa Braïthe , Durand Patrick , Maganga Gael D. , Bouchier Christiane , Schneider Bradley S. , Fair Joseph , Renaud François , Leroy Eric M. 
Published: November 2014

ABSTRACT

Lymphocytic choriomeningitis virus (LCMV) can cause acute fatal disease on all continents but was never detected in Africa. We report the first detection of LCMV RNA in a common European house mouse (
Mus musculus
domesticus
) in Africa. Phylogenetic analyses show a close relationship with North American strains. These findings suggest that there is a risk of the appearance of LCMV acute encephalitis cases. This is a perfect example of virus dissemination by its natural host that may have dramatic public health consequences.
MicroRNA miR-21 Attenuates Human Cytomegalovirus Replication in Neural Cells by Targeting Cdc25a
Authors: Fu Ya-Ru , Liu Xi-Juan , Li Xiao-Jun , Shen Zhang-zhou , Yang Bo , Wu Cong-Cong , Li Jia-Fu , Miao Ling-Feng , Ye Han-Qing , Qiao Guan-Hua , Rayner Simon , Chavanas Stéphane , Davrinche Christian , Britt William J. , Tang Qiyi , McVoy Michael , Mocarski Edward , Luo Min-Hua 
Published: November 2014

ABSTRACTCongenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily manifesting as neurological disorders. HCMV infection alters expression of cellular microRNAs (miRs) and induces cell cycle arrest, which in turn modifies the cellular environment to favor virus replication. Previous observations found that HCMV infection reduces miR-21 expression in neural progenitor/stem cells (NPCs). Here, we show that infection of NPCs and U-251MG cells represses miR-21 while increasing the levels of Cdc25a, a cell cycle regulator and known target of miR-21. These opposing responses to infection prompted an investigation of the relationship between miR-21, Cdc25a, and viral replication. Overexpression of miR-21 in NPCs and U-251MG cells inhibited viral gene expression, genome replication, and production of infectious progeny, while shRNA-knockdown of miR-21 in U-251MG cells increased viral gene expression. In contrast, overexpression of Cdc25a in U-251MG cells increased viral gene expression and production of infectious progeny and overcame the inhibitory effects of miR-21 overexpression. Three viral gene products—IE1, pp71, and UL26—were shown to inhibit miR-21 expression at the transcriptional level. These results suggest that Cdc25a promotes HCMV replication and elevation of Cdc25a levels after HCMV infection are due in part to HCMV-mediated repression of miR-21. Thus, miR-21 is an intrinsic antiviral factor that is modulated by HCMV infection. This suggests a role for miR-21 downregulation in the neuropathogenesis of HCMV infection of the developing CNS.IMPORTANCEHuman cytomegalovirus (HCMV) is a ubiquitous pathogen and has very high prevalence among population, especially in China, and congenital HCMV infection is a major cause for birth defects. Elucidating virus-host interactions that govern HCMV replication in neuronal cells is critical to understanding the neuropathogenesis of birth defects resulting from congenital infection. In this study, we confirm that HCMV infection downregulates miR-21 but upregulates Cdc25a. Further determined the negative effects of cellular miRNA miR-21 on HCMV replication in neural progenitor/stem cells and U-251MG glioblastoma/astrocytoma cells. More importantly, our results provide the first evidence that miR-21 negatively regulates HCMV replication by targeting Cdc25a, a vital cell cycle regulator. We further found that viral gene products of IE1, pp71, and UL26 play roles in inhibiting miR-21 expression, which in turn causes increases in Cdc25a and benefits HCMV replication. Thus, miR-21 appears to be an intrinsic antiviral factor that represents a potential target for therapeutic intervention.
Short Conserved Sequences of HIV-1 Are Highly Immunogenic and Shift Immunodominance
Authors: Yang Otto O. , Ali Ayub , Kasahara Noriyuki , Faure-Kumar Emmanuelle , Bae Jin Young , Picker Louis J. , Park Haesun 
Published: November 2014

ABSTRACT

Cellular immunity is pivotal in HIV-1 pathogenesis but is hampered by viral sequence diversity. An approach to minimize this diversity is to focus immunity on conserved proteome sequences; therefore, we selected four relatively conserved regions (Gag amino acids 148 to 214 and 250 to 335, Env amino acids 521 to 606, and Nef amino acids 106 to 148), each created in three mosaics, to provide better coverage of M-group HIV-1 sequences. A conserved-region vaccine (CRV) delivering genes for these four regions as equal mixtures of three mosaics each (each region at a separate injection site) was compared to a whole-protein vaccine (WPV) delivering equimolar amounts of genes for whole Gag, Env, and Nef as clade B consensus sequences (separate injection sites). Three rhesus macaques were vaccinated via three DNA primes and a recombinant adenovirus type 5 boost (weeks 0, 4, 8, and 24, respectively). Although CRV inserts were about one-fifth that of WPV, the CRV generated comparable-magnitude blood CD4
+
and CD8
+
T lymphocyte responses against Gag, Env, and Nef. WPV responses preferentially targeted proteome areas outside the selected conserved regions in direct proportion to sequence lengths, indicating similar immunogenicities for the conserved regions and the outside regions. The CRV yielded a conserved-region targeting density that was approximately 5-fold higher than that of the WPV. A similar pattern was seen for bronchoalveolar lymphocytes, but with quadruple the magnitudes seen in blood. Overall, these findings demonstrate that the selected conserved regions are highly immunogenic and that anatomically isolated vaccinations with these regions focus immunodominance compared to the case for full-length protein vaccination.

IMPORTANCE
HIV-1 sequence diversity is a major barrier limiting the capability of cellular immunity to contain infection and the ability of vaccines to match circulating viral sequences. To date, vaccines tested in humans have delivered whole proteins or genes for whole proteins, and it is unclear whether including only conserved sequences would yield sufficient cellular immunogenicity. We tested a vaccine delivering genes for four small conserved HIV-1 regions compared to a control vaccine with genes for whole Gag, Env, and Nef. Although the conserved regions ranged from 43 to 86 amino acids and comprised less than one-fifth of the whole Gag/Env/Nef sequence, the vaccines elicited equivalent total magnitudes of both CD4
+
and CD8
+
T lymphocyte responses. These data demonstrate the immunogenicity of these small conserved regions and the potential for a vaccine to steer immunodominance toward conserved epitopes.
Complete Genome Characterization of Recent and Ancient Belgian Pig Group A Rotaviruses and Assessment of Their Evolutionary Relationship with Human Rotaviruses
Authors: Theuns Sebastiaan , Heylen Elisabeth , Zeller Mark , Roukaerts Inge D. M. , Desmarets Lowiese M. B. , Van Ranst Marc , Nauwynck Hans J. , Matthijnssens Jelle 
Published: November 2014

ABSTRACT
Group A rotaviruses (RVAs) are an important cause of diarrhea in young pigs and children. An evolutionary relationship has been suggested to exist between pig and human RVAs. This hypothesis was further investigated by phylogenetic analysis of the complete genomes of six recent (G2P[27], G3P[6], G4P[7], G5P[7], G9P[13], and G9P[23]) and one historic (G1P[7]) Belgian pig RVA strains and of all completely characterized pig RVAs from around the globe. In contrast to the large diversity of genotypes found for the outer capsid proteins VP4 and VP7, a relatively conserved genotype constellation (I5-R1-C1-M1-A8-N1-T7-E1-H1) was found for the other 9 genes in most pig RVA strains. VP1, VP2, VP3, NSP2, NSP4, and NSP5 genes of porcine RVAs belonged to genotype 1, which is shared with human Wa-like RVAs. However, for most of these gene segments, pig strains clustered distantly from human Wa-like RVAs, indicating that viruses from both species have entered different evolutionary paths. However, VP1, VP2, and NSP3 genes of some archival human strains were moderately related to pig strains. Phylogenetic analysis of the VP6, NSP1, and NSP3 genes, as well as amino acid analysis of the antigenic regions of VP7, further confirmed this evolutionary segregation. The present results also indicate that the species barrier is less strict for pig P[6] strains but that chances for successful spread of these strains in the human population are hampered by the better adaptation of pig RVAs to pig enterocytes. However, future surveillance of pig and human RVA strains is warranted.

IMPORTANCE
Rotaviruses are an important cause of diarrhea in many species, including pigs and humans. Our understanding of the evolutionary relationship between rotaviruses from both species is limited by the lack of genomic data on pig strains. In this study, recent and ancient Belgian pig rotavirus isolates were sequenced, and their evolutionary relationship with human Wa-like strains was investigated. Our data show that Wa-like human and pig strains have entered different evolutionary paths. Our data indicate that pig P[6] strains form the most considerable risk for interspecies transmission to humans. However, efficient spread of pig strains in the human population is most likely hampered by the adaptation of some crucial viral proteins to the cellular machinery of pig enterocytes. These data allow a better understanding of the risk for direct interspecies transmission events and the emergence of pig rotaviruses or pig-human reassortants in the human population.
Mutations in HIV-1 Envelope That Enhance Entry with the Macaque CD4 Receptor Alter Antibody Recognition by Disrupting Quaternary Interactions within the Trimer
Authors: Boyd David F. , Peterson Dylan , Haggarty Beth S. , Jordan Andrea P. O. , Hogan Michael J. , Goo Leslie , Hoxie James A. , Overbaugh Julie 
Published: November 2014

ABSTRACTChimeric simian immunodeficiency virus (SIV)/human immunodeficiency virus (HIV) (SHIV) infection of macaques is commonly used to model HIV type 1 (HIV-1) transmission and pathogenesis in humans. Despite the fact that SHIVs encode SIV antagonists of the known macaque host restriction factors, these viruses require additional adaptation for replication in macaques to establish a persistent infection. Additional adaptation may be required in part because macaque CD4 (mCD4) is a suboptimal receptor for most HIV-1 envelope glycoprotein (Env) variants. This requirement raises the possibility that adaptation of HIV-1 Env to the macaque host leads to selection of variants that lack important biological and antigenic properties of the viruses responsible for the HIV-1 pandemic in humans. Here, we investigated whether this adaptation process leads to changes in the antigenicity and structure of HIV-1 Env. For this purpose, we examined how two independent mutations that enhance mCD4-mediated entry, A204E and G312V, impact antibody recognition in the context of seven different parental HIV-1 Env proteins from diverse subtypes. We also examined HIV-1 Env variants from three SHIVs that had been adapted for increased replication in macaques. Our results indicate that these different macaque-adapted variants had features in common, including resistance to antibodies directed to quaternary epitopes and sensitivity to antibodies directed to epitopes in the variable domains (V2 and V3) that are buried in the parental, unadapted Env proteins. Collectively, these findings suggest that adaptation to mCD4 results in conformational changes that expose epitopes in the variable domains and disrupt quaternary epitopes in the native Env trimer.IMPORTANCEThese findings indicate the antigenic consequences of adapting HIV-1 Env to mCD4. They also suggest that to best mimic HIV-1 infection in humans when using the SHIV/macaque model, HIV-1 Env proteins should be identified that use mCD4 as a functional receptor and preserve quaternary epitopes characteristic of HIV-1 Env.
Two Classes of Broadly Neutralizing Antibodies within a Single Lineage Directed to the High-Mannose Patch of HIV Envelope
Authors: Doores Katie J. , Kong Leopold , Krumm Stefanie A. , Le Khoa M. , Sok Devin , Laserson Uri , Garces Fernando , Poignard Pascal , Wilson Ian A. , Burton Dennis R. 
Published: November 2014

ABSTRACT
The high-mannose patch of human immunodeficiency virus (HIV) envelope (Env) elicits broadly neutralizing antibodies (bnAbs) during natural infection relatively frequently, and consequently, this region has become a major target of vaccine design. However, it has also become clear that antibody recognition of the region is complex due, at least in part, to variability in neighboring loops and glycans critical to the epitopes. bnAbs against this region have some shared features and some distinguishing features that are crucial to understand in order to design optimal immunogens that can induce different classes of bnAbs against this region. Here, we compare two branches of a single antibody lineage, in which all members recognize the high-mannose patch. One branch (prototype bnAb PGT128) has a 6-amino-acid insertion in CDRH2 that is crucial for broad neutralization. Antibodies in this branch appear to favor a glycan site at N332 on gp120, and somatic hypermutation is required to accommodate the neighboring V1 loop glycans and glycan heterogeneity. The other branch (prototype bnAb PGT130) lacks the CDRH2 insertion. Antibodies in this branch are noticeably effective at neutralizing viruses with an alternate N334 glycan site but are less able to accommodate glycan heterogeneity. We identify a new somatic variant within this branch that is predominantly dependent on N334. The crystal structure of PGT130 offers insight into differences from PGT128. We conclude that different immunogens may be required to elicit bnAbs that have the optimal characteristics of the two branches of the lineage described.

IMPORTANCE
Development of an HIV vaccine is of vital importance for prevention of new infections, and it is thought that elicitation of HIV bnAbs will be an important component of an effective vaccine. Increasingly, bnAbs that bind to the cluster of high-mannose glycans on the HIV envelope glycoprotein, gp120, are being highlighted as important templates for vaccine design. In particular, bnAbs from IAVI donor 36 (PGT125 to PGT131) have been shown to be extremely broad and potent. Combination of these bnAbs enhanced neutralization breadth considerably, suggesting that an optimal immunogen should elicit several antibodies from this family. Here we study the evolution of this antibody family to inform immunogen design. We identify two classes of bnAbs that differ in their recognition of the high-mannose patch and show that different immunogens may be required to elicit these different classes.
Physician user satisfaction with an electronic medical records system in primary healthcare centres in Al Ain: a qualitative study
Authors: Al Alawi Shamma , Al Dhaheri Aysha , Al Baloushi Durra , Al Dhaheri Mouza , Prinsloo Engela A M 
Published: November 2014

ObjectivesTo explore physician satisfaction with an electronic medical records (EMR) system, to identify and explore the main limitations of the system and finally to submit recommendations to address these limitations.DesignA descriptive qualitative study that entailed three focus group interviews was performed among physicians using open-ended questions. The interviews were audiotaped, documented and transcribed verbatim. The themes were explored and analysed in different categories.SettingThe study was conducted in primary healthcare centres (PHC) in Al Ain, United Arab Emirates (UAE).ParticipantsA total of 23 physicians, all using the same EMR system, attended one of three focus groups held in PHC in Al Ain Medical District. Each focus group consisted of 7–9 physicians working in PHC as family medicine specialists, residents or general practitioners.Primary outcome measurePhysician satisfaction with the EMR system.ResultsKey themes emerged and were categorised as physician-dependent, patient-related and system-related factors. In general, physicians were satisfied with the EMR system in spite of initial difficulties with implementation. Most participants identified that the long time required to do the documentation affected their practice and patient communication. Many physicians expressed satisfaction with the orders and results of laboratory and radiology functions and they emphasised that this was the strongest point in the EMR. They were also satisfied with the electronic prescription function, stating that it reduced errors and saved time.ConclusionsPhysicians are satisfied with the EMR and have a positive perception regarding the application of the system. Several themes emerged during this study that need to be considered to enhance the EMR system. Further studies need to be conducted among other healthcare practitioners and patients to explore their attitude and perception about the EMR.
Evaluation of electronic prescription implementation in polymedicated users of Catalonia, Spain: a population-based longitudinal study
Authors: Lizano-Díez Irene , Modamio Pilar , López-Calahorra Pilar , Lastra Cecilia F , Segú Jose L , Gilabert-Perramon Antoni , Mariño Eduardo L 
Published: November 2014

ObjectivesTo assess whether electronic prescribing is a comprehensive health management tool that may contribute to rational drug use, particularly in polymedicated patients receiving 16 or more medications in the public healthcare system in the Barcelona Health Region (BHR).Design16 months of retrospective study followed by 12 months of prospective monitoring.SettingPrimary healthcare in BHR, Catalonia, Spain.ParticipantsAll insured patients, especially those who are polymedicated in six basic health areas (BHA). Polymedicated patients were those with a consumption of ≥16 drugs/month.InterventionsMonitoring demographic and consumption variables obtained from the records of prescriptions dispensed in pharmacies and charged to the public health system, as well as the resulting drug use indicators. Territorial variables related to implementation of electronic prescribing were also described and were obtained from the institutional data related to the deployment of the project.Main outcome measuresTrend in drug use indicators (number of prescriptions per polymedicated user, total cost per polymedicated user and total cost per prescription) according to e-prescription implementation.ResultsThere was a significant upward trend in the number of polymedicated users, number of prescriptions and total cost (p<0.05), which seemed independent from the implementation of electronic prescribing when comparing the preimplementation and postimplementation period. Prescriptions per user and cost per user showed a decrease between the preimplementation and postimplementation period, being significant in two BHAs (p<0.05).ConclusionsResults suggest that after the implementation of electronic prescribing, the rationality of prescribing in polymedicated patients improved. In addition, this study provides a very valuable approach for future impact assessment.
Project JOINTS: What factors affect bundle adoption in a voluntary quality improvement campaign?
Authors: Khodyakov Dmitry , Ridgely M Susan , Huang Christina , DeBartolo Katherine O , Sorbero Melony E , Schneider Eric C 
Published: November 2014

BackgroundDiffusion and adoption of effective evidence-based clinical practices can be slow, especially if complex changes are required to implement new practices.ObjectiveTo examine how hospital adherence to quality improvement (QI) methods and hospital engagement with a large-scale QI campaign could facilitate the adoption of an enhanced prevention bundle designed to reduce surgical site infection (SSI) rates after orthopaedic surgery (hip and knee arthroplasty).MethodsWe conducted telephone interviews with hospital QI leaders from 73 of the 109 hospitals (67% response rate) in five states that participated in Project JOINTS (JoiningOrganizationsIN TacklingSSIs), a QI campaign run by Institute for Healthcare Improvement (IHI). Using QI methods grounded in the IHI Model for Improvement, this campaign encouraged hospitals to implement an enhanced SSI prevention bundle. Hospital QI leaders reported on their hospital's adherence to the Project JOINTS QI methods; their level of engagement with Project JOINTS activities; and adoption of the SSI prevention bundle components. Interview data were analysed quantitatively and qualitatively.ResultsBoth adherence to the QI methods and hospital engagement were positively associated with complete bundle adoption. Hospital engagement, especially the use of project materials and tools, was also positively associated with the initiation of and improved adherence to individual bundle components.ConclusionsOur findings suggest that greater adherence to the QI methods and active hospital engagement in a QI campaign facilitate adoption of evidence-based patient safety bundles in orthopaedic practice.
Molecular pathology analyses of two fatal human infections of avian influenza A(H7N9) virus
Authors: Feng Yanling , Hu Lvyin , Lu Shuihua , Chen Qingguo , Zheng Ye , Zeng Dong , Zhang Jun , Zhang Anli , Chen Liang , Hu Yunwen , Zhang Zhiyong 
Published: November 2014

AimsTo investigate the histopathological manifestations of two fatal cases of H7N9 influenza A virus infection.MethodsPulmonary and hepatic specimens from two fatal cases of H7N9 influenza virus infection were examined using H&E staining. Additionally, in situ hybridisation was performed with probes (ViewRNA) targeting H7N9 RNA and IP-10, interleukin (IL)-6 mRNA. The distribution of surfactant protein A (SP-A), surfactant protein B (SP-B), CD3, CD4, CD8, CD68 and C4d were determined with immunohistochemistry.Results Apart from the typical diffuse alveolar damage and hyaline membrane observed in severe influenza infection, we detected H7N9 RNA and massive intrapulmonary production of IP-10 and IL-6 mRNA using in situ hybridisation. Hyperplasia of type II pneumocytes was observed by H&E staining and immunohistochemistry. Proliferating macrophages and clustered neutrophils in the infected lungs were observed, whereas T lymphocytes, especially CD4T helper cells, were markedly depleted. No obvious complement deposition was found in lung tissues.Conclusions Our findings suggest that H7N9 influenza virus induced an immunological response towards overt pulmonary inflammation and systemic lymphopenia which led to intense alveolar damage and respiratory failure.