bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordination between respiration and swallowing during non‐invasive positive pressure ventilation
Authors: Hori Ryuji , Isaka Masaaki , Oonishi Kazuhiko , Yabe Toru , Oku Yoshitaka 
Published: March 2016

AbstractBackground and objectiveThe purpose of this study was to test the hypothesis that the risk of silent aspiration is increased in non‐invasive positive pressure ventilation.MethodsWe analysed the coordination between respiration and swallowing, in 12 young volunteers and 10 elder volunteers, by simultaneously monitoring respiratory flow, laryngeal movement and swallowing sound in three different conditions: control, continuous positive airway pressure (CPAP), and bi‐level positive airway pressure (BiPAP). A step‐wise multiple regression analysis was performed with the occurrence rate of inspiration after swallows as the dependent variable and various correlated variables as the independent variables.ResultsIn both subject groups, the occurrence rate of inspiration after swallow was greater with BiPAP compared with control and CPAP conditions. Repetitive saliva swallowing test count and swallow non‐inspiratory flow occurrence rate were extracted as predictor variables for risk of inspiration after swallows during BiPAP treatment.ConclusionWe found that the occurrence rate of inspiration after swallow is increased with BiPAP use irrespective of age. The results suggest that swallow non‐inspiratory flow may trigger inspiratory support in the BiPAP mode, resulting in a risk of aspiration.
Zircon U–Pb and Molybdenite Re–Os Ages of the Lakange Porphyry Cu–Mo Deposit, Gangdese Porphyry Copper Belt, Southern Tibet, China
Authors: Leng Qiu‐Feng , Tang Ju‐Xing , Zheng Wen‐bao , Lin Bin , Tang Pan , Wang Hao , Li Hai‐Feng 
Published: March 2016

AbstractThe Lakange porphyry Cu–Mo deposit within the Gangdese metallogenic belt of Tibet is located in the southern–central part of the eastern Lhasa block, in the Tibetan Tethyan tectonic domain. This deposit is one of the largest identified by a joint Qinghai–Tibetan Plateau geological survey project undertaken in recent years. Here, we present the results of the systematic logging of drillholes and provide new petrological, zircon U–Pb age, and molybdenite Re–Os age data for the deposit. The ore‐bearing porphyritic granodiorite contains elevated concentrations of silica and alkali elements but low concentrations of MgO and CaO. It is metaluminous to weakly peraluminous and has A/CNK values of 0.90–1.01. The samples contain low total REE concentrations and show light REE/heavy REE (LREE/HREE) ratios of 17.51–19.77 and (La/Yb)N values of 29.65–41.05. The intrusion is enriched in the large‐ion lithophile elements (LILE) and depleted in the HREE and high field‐strength elements (HFSE). The ore‐bearing porphyritic granodiorite yielded a Miocene zircon U–Pb crystallization age of 13.58 ± 0.42 Ma, whereas the mineralization within the Lakange deposit yielded Miocene molybdenite Re–Os ages of 13.20 ± 0.20 and 13.64 ± 0.21, with a weighted mean of 13.38 ± 0.15 Ma and an isochron age of 13.12 ± 0.44 Ma. This indicates that the crystallization and mineralization of the Lakange porphyry were contemporaneous. The ore‐bearing porphyritic granodiorite yielded zircon εHf(t) values between −3.99 and 4.49 (mean, −0.14) and two‐stage model ages between 1349 and 808 Myr (mean, 1103 Myr). The molybdenite within the deposit contains 343.6–835.7 ppm Re (mean, 557.8 ppm). These data indicate that the mineralized porphyritic granodiorite within the Lakange deposit is adakitic and formed from parental magmas derived mainly from juvenile crustal material that partly mixed with older continental crust during the evolution of the magmas. The Lakange porphyry Cu–Mo deposit and numerous associated porphyry–skarn deposits in the eastern Gangdese porphyry copper belt (17–13 Ma) formed in an extensional tectonic setting during the India–Asia continental collision.
Oral health services within community‐based organizations for young children with special health care needs
Authors: Cruz Stephanie , Chi Donald L. , Huebner Colleen E. 
Published: March 2016

ABSTRACTPurposeTo identify the types of oral health services offered by community‐based organizations to young children with special health care needs (CSHCN) and the barriers and facilitators to the provision of these in a nonfluoridated community.MethodsThirteen key informant interviews with representatives from early intervention agencies, advocacy groups, and oral health programs who provide services to CSHCN in Spokane county, Washington. We used a content analysis to thematically identify oral health services as proactive or incidental and the barriers and facilitators to their provision.ResultsWe identified four types of oral health services: screenings, parent education, preventive dental care, and dental referrals. Barriers to providing all four services included limited agency resources, restrictive administrative and system‐level policies, and low demand from parents. A barrier to providing education and preventive dental care was community disagreement regarding fluoride. A barrier to providing dental referrals was the perceived lack of dentists who could treat CSHCN. Facilitators included community partnerships among the organizations and utilization of the statewide oral health program.ConclusionsOral health services for young CSHCN are limited and often delivered in response to oral health problems. Coordinated efforts between community‐based organizations, health providers, and advocates are necessary to ensure the provision of comprehensive care, including preventive and restorative services, to all young CSHCN.
Reduced alloimmunization in mice following repeated transfusion with pathogen‐reduced platelets
Authors: Muench Marcus O. , Heitman John W. , Inglis Heather , Fomin Marina E. , Marschner Susanne , Goodrich Raymond P. , Norris Philip J. , Jackman Rachael P. 
Published: March 2016

BACKGROUNDAllogeneic transfusion can result in alloimmunization, leading to platelet (PLT) refractoriness and rejection of solid organ transplants. Previously we demonstrated that pathogen reduction using UV light and riboflavin (UV + R) eliminates the immunogenicity of white blood cells (WBCs) in vitro, blocks alloimmunization from transfusion in mice, and results in reduced ex vivo cytokine responses to subsequent untreated transfusions. We sought to determine if repeated transfusion with pathogen‐reduced PLT‐rich plasma (PRP) would eventually cause breakthrough alloimmunization or enhanced tolerance.STUDY DESIGN AND METHODSBALB/cJ mice were transfused weekly for 2, 4, or 8 weeks with C57Bl/6J PRP that was either untreated or pathogen reduced with UV + R and leukoreduced or not. Alloimmunization was determined by measuring donor antibody levels, ex vivo cytokine responses, and 24‐hour donor PLT recovery. The role of donor antibodies in PLT refractoriness was also assessed by transfer of diluted immune sera into naïve recipients.RESULTSDonor antibody levels increased with the number of transfusions, but levels were significantly reduced using either UV + R or leukoreduction, and combining UV + R and leukoreduction gave the best protection. Priming of ex vivo cytokine responses required WBCs and remained suppressed with repeated UV + R–treated transfusion. PLT recovery was reduced with UV + R in naïve mice, and multiply transfused mice had poor PLT recovery even when antibody levels were relatively low. Approximately 1/100 dose of serum from a multiply transfused mouse was sufficient for complete rejection of donor PLTs.CONCLUSIONSPathogen reduction significantly reduces alloimmunization in repeatedly transfused mice and combined with leukoreduction provides a high level of protection from alloimmunization.
Myocardial triggers involved in activation of remote ischaemic preconditioning
Authors: Donato Martín , Goyeneche María A. , Garces Mariana , Marchini Timoteo , Pérez Virginia , del Mauro Julieta , Höcht Christian , Rodríguez Manuel , Evelson Pablo , Gelpi Ricardo J. 
Published: March 2016

New Findings
What is the central question of this study?
Ischaemia–reperfusion of peripheral tissues protects the heart from subsequent myocardial ischaemia–reperfusion injury, a phenomenon referred to as remote ischaemic preconditioning (rIPC). This study evaluated the possible myocardial triggers of rIPC.
What is the main finding and its importance?
Remote ischaemic preconditioning reduces infarct size through a vagal pathway and a mechanism involving phosphorylation of Akt and endothelial nitric oxide synthase, opening of mitochondrial ATP‐dependent K+ channels and an increase in mitochondrial H2O2 production. All these phenomena occur before the myocardial ischaemia; hence, they could act as ‘triggers’ of rIPC.It has been proposed that remote ischaemic preconditioning (rIPC) activates a parasympathetic neural pathway. However, the myocardial intracellular mechanism of rIPC remains unclear. Here, we characterized some of the intracellular signals participating as rIPC triggers. Isolated rat hearts were subjected to 30 min of global ischaemia and 120 min of reperfusion (Non‐rIPC group). In a second group, before the isolation of the heart, an rIPC protocol (three cycles of hindlimb ischaemia–reperfusion) was performed. The infarct size was measured with tetrazolium staining. Expression/phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) and mitochondrial H2O2 production were evaluated at the end of the rIPC protocol, before myocardial ischaemia–reperfusion. The rIPC significantly decreased the infarct size and induced Akt and eNOS phosphorylation. The protective effect on infarct size was abolished by cervical vagal section, l‐NAME (an NO synthesis inhibitor) and 5‐hydroxydecanoate (a mitochondrial ATP‐dependent K+ channel blocker). Mitochondrial production of H2O2 was increased by rIPC, whereas it was abolished by cervical vagal section, l‐NAME and 5‐hydroxydecanoate. We conclude that rIPC activates a parasympathetic vagal pathway and a mechanism involving the phosphorylation of Akt and eNOS, the opening of mitochondrial ATP‐dependent K+ channels and the release of H2O2 by the mitochondria. All these phenomena occur before myocardial ischaemia and could act as triggers of rIPC.
Auto-Assembling Detoxified Staphylococcus aureus Alpha-Hemolysin Mimicking the Wild-Type Cytolytic Toxin
Authors: Fiaschi Luigi , Di Palo Benedetta , Scarselli Maria , Pozzi Clarissa , Tomaszewski Kelly , Galletti Bruno , Nardi-Dei Vincenzo , Arcidiacono Letizia , Mishra Ravi P. N. , Mori Elena , Pallaoro Michele , Falugi Fabiana , Torre Antonina , Fontana Maria Rita , Soriani Marco , Bubeck Wardenburg Juliane , Grandi Guido , Rappuoli Rino , Ferlenghi Ilaria , Bagnoli Fabio 
Published: March 2016

ABSTRACT

Staphylococcus aureus
alpha-hemolysin (Hla) assembles into heptameric pores on the host cell membrane, causing lysis, apoptosis, and junction disruption. Herein, we present the design of a newly engineered
S. aureus
alpha-toxin, HlaPSGS, which lacks the predicted membrane-spanning stem domain. This protein is able to form heptamers in aqueous solution in the absence of lipophilic substrata, and its structure, obtained by transmission electron microscopy and single-particle reconstruction analysis, resembles the cap of the wild-type cytolytic Hla pore. HlaPSGS was found to be impaired in binding to host cells and to its receptor ADAM10 and to lack hemolytic and cytotoxic activity. Immunological studies using human sera as well as sera from mice convalescent from
S. aureus
infection suggested that the heptameric conformation of HlaPSGS mimics epitopes exposed by the cytolytic Hla pore during infection. Finally, immunization with this newly engineered Hla generated high protective immunity against staphylococcal infection in mice. Overall, this study provides unprecedented data on the natural immune response against Hla and suggests that the heptameric HlaPSGS is a highly valuable vaccine candidate against
S. aureus
.
Diagnostic Accuracy of the Small Membrane Filtration Method for Diagnosis of Pulmonary Tuberculosis in a High-HIV-Prevalence Setting
Authors: Boum Yap , Kim Soyeon , Orikiriza Patrick , Acuña-Villaorduña Carlos , Vinhas Solange , Bonnet Maryline , Nyehangane Dan , Mwanga-Amumpaire Juliet , Fennelly Kevin P. , Jones-López Edward C. 
Published: March 2016

ABSTRACT
Sputum acid-fast bacilli (AFB) smear microscopy has suboptimal sensitivity but remains the most commonly used laboratory test to diagnose pulmonary tuberculosis (TB). We prospectively evaluated the small membrane filtration (SMF) method that concentrates AFB in a smaller area to facilitate detection to improve the diagnostic performance of microscopy. We enrolled adults with suspicion of pulmonary TB from health facilities in southwestern Uganda. Clinical history, physical examination, and 3 sputum samples were obtained for direct fluorescent AFB smear, SMF, Xpert MTB/RIF, and MGIT culture media. Sensitivity and specificity were estimated for SMF, AFB smear, and Xpert MTB/RIF, using MGIT as the reference standard. The analysis was stratified according to HIV status. From September 2012 to April 2014, 737 participants were included in the HIV-infected stratum (146 [20.5%] were culture positive) and 313 were in the HIV-uninfected stratum (85 [28%] were culture positive). In HIV-infected patients, the sensitivity of a single SMF was 67.4% (95% confidence interval [CI], 59.9% to 74.1%); for AFB, 68.0% (95% CI, 60.6% to 74.6%); and for Xpert MTB/RIF, 91.0% (95% CI, 85.0% to 94.8%). In HIV-uninfected patients, the corresponding sensitivities were 72.5% (95% CI, 62.1% to 80.9%), 80.3% (95% CI, 70.8% to 87.2%), and 93.5% (95% CI, 85.7% to 97.2%). The specificity for all 3 tests in both HIV groups was ≥96%. In this setting, the SMF method did not improve the diagnostic accuracy of sputum AFB. The Xpert MTB/RIF assay performed well in both HIV-infected and -uninfected groups.
Anatomic, Geographic, and Taxon-Specific Relative Risks of Carbapenem Resistance in the Health Care System of the U.S. Department of Defense
Authors: Lesho Emil , Chukwuma Uzo , Sparks Michael , Neumann Charlotte , Richesson Douglas , Clifford Robert , Gierhart Sarah , Waterman Paige , Hinkle Mary 
Published: March 2016

ABSTRACT

Carbapenem-resistant
Pseudomonas
aeruginosa,
Acinetobacter
spp., and
Enterobacteriaceae
pose urgent public health threats. The differential burden, relative risks, associations with antimicrobial consumption, and temporal trends of those taxa in large, geographically diverse U.S. health systems remain under reported. Electronic records of all patients in a geographically dispersed 280-hospital managed-care system from 2005 to 2014 were reviewed. Carbapenem-resistant strains were identified based on Clinical and Laboratory Standards Institute guidelines and breakpoints. A total of 360,000 potentially carbapenem-resistant strains were identified from 14.7 million cultures (80% infecting and 20% surveillance). Isolation of bacteria overseas or isolation from the bloodstream was associated with a higher relative risks of carbapenem resistance (CR;
P
< 0.0001).
Enterobacteriaceae
were isolated 11 times more frequently than
P. aeruginosa
and
Acinetobacter
spp. However, compared to
Enterobacteriaceae
, the CR levels were 73-fold and 210-fold higher in P. aeruginosa and
Acinetobacter
spp., respectively. Significant differences in the relative risk of CR between taxa, anatomic, and geographic locations persisted after adjustment for other variables, the biggest differences occurring between taxa. Overall, CR rates increased for
Enterobacteriaceae
(
P
= 0.03) and decreased for Acinetobacter spp. and P. aeruginosa (
P
< 0.0001). These data provide a useful baseline for resistance trending and have implications for surveillance. Infections acquired overseas and bloodstream infections are particularly important areas for continued monitoring.
Identification of the Fusion Peptide-Containing Region in Betacoronavirus Spike Glycoproteins
Authors: Ou Xiuyuan , Zheng Wangliang , Shan Yiwei , Mu Zhixia , Dominguez Samuel R. , Holmes Kathryn V. , Qian Zhaohui 
Published: March 2016

ABSTRACT

The fusion peptides (FP) play an essential role in fusion of viral envelope with cellular membranes. The location and properties of the FPs in the spike (S) glycoproteins of different coronaviruses (CoV) have not yet been determined. Through amino acid sequence analysis of S proteins of representative CoVs, we identified a common region as a possible FP (pFP) that shares the characteristics of FPs of class I viral fusion proteins, including high Ala/Gly content, intermediate hydrophobicity, and few charged residues. To test the hypothesis that this region contains the CoV FP, we systemically mutated every residue in the pFP of Middle East respiratory syndrome betacoronavirus (MERS-CoV) and found that 11 of the 22 residues in the pFP (from G953 to L964, except for A956) were essential for S protein-mediated cell-cell fusion and virus entry. The synthetic MERS-CoV pFP core peptide (
955
IAGVGWTAGL
964
) induced extensive fusion of liposome membranes, while mutant peptide failed to induce any lipid mixing. We also selectively mutated residues in pFPs of two other β-CoVs, severe acute respiratory syndrome coronavirus (SARS-CoV) and mouse hepatitis virus (MHV). Although the amino acid sequences of these two pFPs differed significantly from that of MERS-CoV and each other, most of the pFP mutants of SARS-CoV and MHV also failed to mediate membrane fusion, suggesting that these pFPs are also the functional FPs. Thus, the FPs of 3 different lineages of β-CoVs are conserved in location within the S glycoproteins and in their functions, although their amino acid sequences have diverged significantly during CoV evolution.

IMPORTANCE
Within the class I viral fusion proteins of many enveloped viruses, the FP is the critical mediator of fusion of the viral envelope with host cell membranes leading to virus infection. FPs from within a virus family, like influenza viruses or human immunodeficiency viruses (HIV), tend to share high amino acid sequence identity. In this study, we determined the location and amino acid sequences of the FPs of S glycoproteins of 3 β-CoVs, MERS-CoV, SARS-CoV, and MHV, and demonstrated that they were essential for mediating cell-cell fusion and virus entry. Interestingly, in marked contrast to the FPs of influenza and HIV, the primary amino acid sequences of the FPs of β-CoVs in 3 different lineages differed significantly. Thus, during evolution the FPs of β-CoVs have diverged significantly in their primary sequences while maintaining the same essential biological functions. Our findings identify a potential new target for development of drugs against CoVs.
Quantitation of Productively Infected Monocytes and Macrophages of Simian Immunodeficiency Virus-Infected Macaques
Authors: Avalos Claudia R. , Price Sarah L. , Forsyth Ellen R. , Pin Julia N. , Shirk Erin N. , Bullock Brandon T. , Queen Suzanne E. , Li Ming , Gellerup Dane , O'Connor Shelby L. , Zink M. Christine , Mankowski Joseph L. , Gama Lucio , Clements Janice E. 
Published: March 2016

ABSTRACT

Despite the success of combined antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains a lifelong infection because of latent viral reservoirs in infected patients. The contribution of CD4
+
T cells to infection and disease progression has been extensively studied. However, during early HIV infection, macrophages in brain and other tissues are infected and contribute to tissue-specific diseases, such as encephalitis and dementia in brain and pneumonia in lung. The extent of infection of monocytes and macrophages has not been rigorously assessed with assays comparable to those used to study infection of CD4
+
T cells and to evaluate the number of CD4
+
T cells that harbor infectious viral genomes. To assess the contribution of productively infected monocytes and macrophages to HIV- and simian immunodeficiency virus (SIV)-infected cells
in vivo
, we developed a quantitative virus outgrowth assay (QVOA) based on similar assays used to quantitate CD4
+
T cell latent reservoirs in HIV- and SIV-infected individuals in whom the infection is suppressed by ART. Myeloid cells expressing CD11b were serially diluted and cocultured with susceptible cells to amplify virus. T cell receptor β RNA was measured as a control to assess the potential contribution of CD4
+
T cells in the assay. Virus production in the supernatant was quantitated by quantitative reverse transcription-PCR. Productively infected myeloid cells were detected in blood, bronchoalveolar lavage fluid, lungs, spleen, and brain, demonstrating that these cells persist throughout SIV infection and have the potential to contribute to the viral reservoir during ART.

IMPORTANCE
Infection of CD4
+
T cells and their role as latent reservoirs have been rigorously assessed; however, the frequency of productively infected monocytes and macrophages
in vivo
has not been similarly studied. Myeloid cells, unlike lymphocytes, are resistant to the cytopathic effects of HIV. Moreover, tissue-resident macrophages have the ability to self-renew and persist in the body for months to years. Thus, tissue macrophages, once infected, have the characteristics of a potentially stable viral reservoir. A better understanding of the number of productively infected macrophages is crucial to further evaluate the role of infected myeloid cells as a potential viral reservoir. In the study described here we compared the frequency of productively infected CD4
+
T cells and macrophages in an SIV-infected macaque model. We developed a critical assay that will allow us to quantitate myeloid cells containing viral genomes that lead to productive infection in SIV-infected macaques and assess the role of macrophages as potential reservoirs.
A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks Viral Pathogenesis and Prevents Corneal Immunopathology via Humoral Immunity
Authors: Royer Derek J. , Gurung Hem R. , Jinkins Jeremy K. , Geltz Joshua J. , Wu Jennifer L. , Halford William P. , Carr Daniel J. J. 
Published: March 2016

ABSTRACTCorrelates of immunologic protection requisite for an efficacious herpes simplex virus 1 (HSV-1) vaccine remain unclear with respect to viral pathogenesis and clinical disease. In the present study, mice were vaccinated with a novel avirulent, live attenuated virus (0ΔNLS) or an adjuvanted glycoprotein D subunit (gD-2) similar to that used in several human clinical trials. Mice vaccinated with 0ΔNLS showed superior protection against early viral replication, neuroinvasion, latency, and mortality compared to that of gD-2-vaccinated or naive mice following ocular challenge with a neurovirulent clinical isolate of HSV-1. Moreover, 0ΔNLS-vaccinated mice exhibited protection against ocular immunopathology and maintained corneal mechanosensory function. Vaccinated mice also showed suppressed T cell activation in the draining lymph nodes following challenge. Vaccine efficacy correlated with serum neutralizing antibody titers. Humoral immunity was identified as the correlate of protection against corneal neovascularization, HSV-1 shedding, and latency through passive immunization. Overall, 0ΔNLS affords remarkable protection against HSV-1-associated ocular sequelae by impeding viral replication, dissemination, and establishment of latency.IMPORTANCEHSV-1 manifests in a variety of clinical presentations ranging from a rather benign “cold sore” to more severe forms of infection, including necrotizing stromal keratitis and herpes simplex encephalitis. The present study was undertaken to evaluate a novel vaccine to ocular HSV-1 infection not only for resistance to viral replication and spread but also for maintenance of the visual axis. The results underscore the necessity to reconsider strategies that utilize attenuated live virus as opposed to subunit vaccines against ocular HSV-1 infection.