bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance-Enhancing Drugs I: Understanding the Basics of Testing for Banned Substances
Authors: Cadwallader Amy B. , Murray Bob
Published: February 2015

Whenever athletes willfully or accidentally ingest performance-enhancing drugs or other banned substances (such as drugs of abuse), markers of those drugs can be detected in biological samples (e.g., biofluids: urine, saliva, blood); in the case of some drugs, that evidence can be apparent for many weeks following the last exposure to the drug. In addition to the willful use of prohibited drugs, athletes can accidentally ingest banned substances in contaminated dietary supplements or foods and inadvertently fail a drug test that could mean the end of an athletic career and the loss of a good reputation. The proliferation of performance-enhancing drugs and methods has required a corresponding increase in the analytical tools and methods required to identify the presence of banned substances in biofluids. Even though extraordinary steps have been taken by organizations such as the World Anti-Doping Agency to limit the use of prohibited substances and methods by athletes willing to cheat, it is apparent that some athletes continue to avoid detection by using alternative doping regimens or taking advantage of the limitations in testing methodologies. This article reviews the testing standards and analytical techniques underlying the procedures used to identify banned substances in biological samples, setting the stage for future summaries of the testing required to establish the use of steroids, stimulants, diuretics, and other prohibited substances.
Time-To-Contact Analysis of Gait Stability in the Swing Phase of Walking in People With Multiple Sclerosis
Authors: Remelius Jebb G. , van Emmerik Richard E.A.
Published: February 2015

This study investigated timing and coordination during the swing phase of swing leg, body center of mass (CoM) and head during walking people with multiple sclerosis (MS; n = 19) and controls (n = 19). The MS group showed differences in swing phase timing at all speeds. At imposed but not preferred speeds, the MS group had less time to prepare for entry into the unstable equilibrium, as the CoM entered this phase of swing earlier. Time-to-contact coupling, quantifying the coordination between the CoM and the swing foot, was not different between groups. The projection of head motion on the ground occurred earlier after toeoff and was positioned closer to the body in the MS group, illustrating increased reliance on visual exproprioception in which vision of the body in relation to the surface of support is established. Finally, prospective control, linking head movements to the swing foot time-to-contact and next step landing area, was impaired in the MS group at higher gait speeds.
Rethinking the marine carbon cycle: Factoring in the multifarious lifestyles of microbes
Authors: Worden Alexandra Z. , Follows Michael J. , Giovannoni Stephen J. , Wilken Susanne , Zimmerman Amy E. , Keeling Patrick J.
Published: February 2015

Changing tastes in marine microbe food webs

Protists are single-celled organisms complete with nuclei, organelles, and symbionts, and possess a multiplicity of physiological talents. They are ubiquitous, abundant, and often neglected by science. Worden
et al.
review the challenges of understanding the role protists play in geochemical cycling in the oceans. These organisms can photosynthesize like plants, graze on bacteria and archaea, parasitize each other and bigger creatures, have sex, and sometimes do all these things serially as conditions change. Their activities may have a significant influence on carbon cycling, and research efforts need to be amplified to understand their functional importance in marine ecosystems.

Science
, this issue
10.1126/science.1257594
Evolutionary development in basal mammaliaforms as revealed by a docodontan
Authors: Luo Zhe-Xi , Meng Qing-Jin , Ji Qiang , Liu Di , Zhang Yu-Guang , Neander April I.
Published: February 2015

Taking advantage of new neighborhoods

Mammals are one of the most morphologically diverse organisms, with adaptation to unique ecological conditions creating a wide array of forms, from mice to whales. Two new basal mammals from the mid-Jurassic period suggest that this diversification was well under way millions of years earlier than previously thought. Luo
et al.
describe a burrowing species with limb and digit modifications similar to those of current burrowers and identify the likely genes and developmental pathways involved. Meng
et al.
describe an arboreal species with modifications for climbing and that possessed teeth clearly adapted for a herbivorous diet, including the consumption of sap.

Science
, this issue p.
760
, p.
764
Ebola drug trials lurch ahead
Authors: Kupferschmidt Kai , Cohen Jon
Published: February 2015

Changing epidemiology and hints of success alter studies of experimental treatments.
Sustainable goals from U.N. under fire
Authors: Stokstad Erik
Published: February 2015

Scientific review labels development targets as vague, weak, or meaningless.
Fund climate intervention research, study says
Authors: Kintisch Eli
Published: February 2015

U.S. needs more science to understand sun-blocking, carbon-removal technologies.
Models predict longer, deeper U.S. droughts
Authors: Underwood Emily
Published: February 2015

Future western “megadroughts” could be worse than ever.
Who are the Tibetans?
Authors: Qiu Jane
Published: February 2015

China and some scientists say they are Chinese. But others see a richer picture.
Built for tough conditions
Authors: Politi Yael , Weaver James C.
Published: February 2015

High-resolution structural data help to explain the mechanical properties of rodent teeth

[Also see Report by

Gordon
et al.

]
Harnessing weak interactions for enantioselective catalysis
Authors: Lu Tongxiang , Wheeler Steven E.
Published: February 2015

The traditional tools of physical organic chemistry benefit from modern data analysis techniques

[Also see Research Article by

Milo
et al.

]
Breaking the intestinal barrier to deliver drugs
Authors: Artursson Per , Knight Stefan D.
Published: February 2015

The structure of a tight junction protein bound to a disruptive toxin may guide drug delivery strategies

[Also see Report by

Saitoh
et al.

]
Give soils their due
Authors: Wall Diana H. , Six Johan
Published: February 2015

We are not paying enough attention to the world's soils, a “nearly forgotten resource” and our “silent ally,” 33% of which are in a state of degradation.
*
We can't breathe, eat, drink, or be healthy without sustainably managing soils. So in recognizing 2015 as the International Year of Soils, the United Nations (UN) is focusing global attention on the increasing pressures on soils and their ripple effect on other global challenges.
Species Typing in Dermal Leishmaniasis
Authors: Van der Auwera Gert , Dujardin Jean-Claude
Published: February 2015

Leishmaniais an infectious protozoan parasite related to African and American trypanosomes. AllLeishmaniaspecies that are pathogenic to humans can cause dermal disease. When one is confronted with cutaneous leishmaniasis, identification of the causative species is relevant in both clinical and epidemiological studies, case management, and control. This review gives an overview of the currently existing and most used assays for species discrimination, with a critical appraisal of the limitations of each technique. The consensus taxonomy for the genus is outlined, including debatable species designations. Finally, a numerical literature analysis is presented that describes which methods are most used in various countries and regions in the world, and for which purposes.
Assessment of the IgA Immunosorbent Agglutination Assay for the Diagnosis of Congenital Toxoplasmosis on a Series of 145 Toxoplasmic Seroconversions
Authors: Murat J. B. , Souvignet A. , Fricker-Hidalgo H. , Brenier-Pinchart M. P. , Bost-Bru C. , Pelloux H.
Published: February 2015

A retrospective analysis of 145 medical records from our teaching hospital laboratory showed an overall specificity of greater than 97% for the IgA immunosorbent agglutination assay (ISAGA A) performed on the sera of babies to diagnose congenital toxoplasmosis (CT). These actualized data emphasize the ability of this test to confirm a diagnosis of congenital toxoplasmosis.
H9N2 Influenza Whole Inactivated Virus Combined with Polyethyleneimine Strongly Enhances Mucosal and Systemic Immunity after Intranasal Immunization in Mice
Authors: Qin Tao , Yin Yinyan , Huang Lulu , Yu Qinghua , Yang Qian
Published: February 2015

Influenza whole inactivated virus (WIV) is more immunogenic and induces protective antibody responses compared with other formulations, like split virus or subunit vaccines, after intranasal mucosal delivery. Polyethyleneimine (PEI), an organic polycation, is widely used as a reagent for gene transfection and DNA vaccine delivery. Although PEI recently has demonstrated potent mucosal adjuvant activity for viral subunit glycoprotein antigens, its immune activity with H9N2 WIV is not well demonstrated. Here, mice were immunized intranasally with H9N2 WIV combined with PEI, and the levels of local respiratory tract and systemic immune responses were measured. Compared to H9N2 WIV alone, antigen-specific IgA levels in the local nasal cavity, trachea, and lung, as well as levels of IgG and its subtypes (IgG1 and IgG2a) in the serum, were strongly enhanced with the combination. Similarly, the activation and proliferation of splenocytes were markedly increased. In addition, PEI is superior as an H9N2 WIV delivery system due to its ability to greatly increase the viral adhesion to mucosal epithelial cells and to enhance the cellular uptake and endosomal escape of antigens in dendritic cells (DCs) and further significantly activate DCs to mature. Taken together, these results provided more insights that PEI has potential as an adjuvant for H9N2 particle antigen intranasal vaccination.
Impact of a Rapid Microarray-Based Assay for Identification of Positive Blood Cultures for Treatment Optimization for Patients with Streptococcal and Enterococcal Bacteremia
Authors: Roshdy Danya G. , Tran Anthony , LeCroy Nicholas , Zeng Donglin , Ou Fang-shu , Daniels Lindsay M. , Weber David J. , Alby Kevin , Miller Melissa B.
Published: February 2015

Implementation of the Verigene Gram-positive blood culture test led to reductions in time to acceptable antibiotic overall (1.9 versus 13.2 h, respectively;
P
= 0.04) and time to appropriate antibiotic for patients with vancomycin-resistant
Enterococcus
(4.2 versus 43.7 h;
P
= 0.006) and viridans group
Streptococcus
(0.2 versus 7.1 h;
P
= 0.02).
Commentaries: Integration of Whole-Genome Sequencing into Infection Control Practices: the Potential and the Hurdles
Authors: Robilotti Elizabeth , Kamboj Mini
Published: February 2015

Microbial whole-genome sequencing (WGS) is poised to transform many of the currently used approaches in medical microbiology. Recent reports on the application of WGS to understand genetic evolution and reconstruct transmission pathways have provided valuable information that will influence infection control practices. While this technology holds great promise, obstacles to full implementation remain. Two articles in this issue of the Journal of Clinical Microbiology (
S. Octavia, Q. Wang, M. M. Tanaka, S. Kaur, V. Sintchenko, and R. Lan
, J Clin Microbiol 53:1063–1071, 2015, doi:
10.1128/JCM.03235-14
, and
S. J. Salipante, D. J. SenGupta, L. A. Cummings, T. A. Land, D. R. Hoogestraat, and B. T. Cookson
, J Clin Microbiol 53:1072–1079, 2015, doi:
10.1128/JCM.03385-14
) describe the breadth of application of WGS to the field of clinical epidemiology.
Bacteremia Caused by Arcobacter butzleri in an Immunocompromised Host
Authors: Arguello Esther , Otto Caitlin C. , Mead Peter , Babady N. Esther
Published: February 2015

Arcobacter butzleri
is an emerging pathogen that has been implicated as the causative agent of persistent watery diarrhea. We describe a case involving a patient with chronic lymphocytic leukemia who developed invasive
A. butzleri
bacteremia. This case illustrates the unique challenges involved in diagnosing infections caused by emerging gastrointestinal pathogens.
Cellular Profiles of Bronchoalveolar Lavage Fluid and Their Prognostic Significance for Non-HIV-Infected Patients with Pneumocystis jirovecii Pneumonia
Authors: Lee Ju Young , Park Hyun Jung , Kim Yong Kyun , Yu Shinae , Chong Yong Pil , Kim Sung-Han , Sung Heungsup , Lee Sang-Oh , Kim Mi-Na , Lim Chae-Man , Kim Yang Soo , Koh Younsuck , Woo Jun Hee , Choi Sang-Ho
Published: February 2015

The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in non-human immunodeficiency virus (HIV)-infected patients with
Pneumocystis jirovecii
pneumonia (PCP) has not been adequately evaluated. The objective of this study was to analyze the cellular profiles of BAL fluid and to evaluate their prognostic significance in non-HIV-infected patients with PCP. A 7-year retrospective cohort study of 166 non-HIV-infected adult patients with PCP who underwent BAL was performed in a tertiary care hospital. The median total BAL fluid white blood cell count was 180/μl (interquartile range, 80 to 330) and was unaffected by the severity of PCP. The median percentages of BAL fluid neutrophils, lymphocytes, and alveolar macrophages were 13.1%, 31.7%, and 30.2%, respectively. The median percentage of BAL fluid neutrophils was significantly higher in severe than in mild-to-moderate PCP (20.4% versus 6.0%,
P
< 0.001), as was the absolute neutrophil count (24/μl versus 13/μl,
P
= 0.001). The percentage of BAL fluid neutrophils was an independent predictor of 30-day (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI], 1.01 to 1.03) and 60-day (aOR, 1.02; 95% CI, 1.01 to 1.04) mortalities. The 30-day and 60-day mortalities increased at rates of 15% (
P
= 0.006) and 21% (
P
< 0.001) per 10% increment of BAL fluid neutrophil levels, respectively. The degree of BAL fluid pleocytosis was relatively low without regard to the severity of PCP. The percentage of BAL fluid neutrophils can be used as a prognostic marker in non-HIV-infected patients with PCP.
Toscana Virus Encephalitis in a Traveler Returning to the United States
Authors: Howell Benjamin A. , Azar Marwan M. , Landry Marie L. , Shaw Albert C.
Published: February 2015

In Italy, Toscana virus is the most common cause of meningitis from May to October. Though only a few cases have been reported in U.S. travelers returning from Europe, most cases are likely unrecognized due to lack of familiarity with the disease. Here, we describe the case of an 82-year-old man presenting with fever, profound weakness, and hearing loss after returning to the United States following a 2-week summertime vacation in southern Italy who was ultimately diagnosed with Toscana virus encephalitis. This case should alert clinicians to the possibility of Toscana virus infection in returning travelers and provides information on how to obtain testing if Toscana virus is suspected.
Domestic Pigs Are Susceptible to Infection with Influenza B Viruses
Authors: Ran Zhiguang , Shen Huigang , Lang Yuekun , Kolb Elizabeth A. , Turan Nuri , Zhu Laihua , Ma Jingjiao , Bawa Bhupinder , Liu Qinfang , Liu Haixia , Quast Megan , Sexton Gabriel , Krammer Florian , Hause Ben M. , Christopher-Hennings Jane , Nelson Eric A. , Richt Juergen , Li Feng , Ma Wenjun
Published: February 2015

Influenza B virus (IBV) causes seasonal epidemics in humans. Although IBV has been isolated from seals, humans are considered the primary host and reservoir of this important pathogen. It is unclear whether other animal species can support the replication of IBV and serve as a reservoir. Swine are naturally infected with both influenza A and C viruses. To determine the susceptibility of pigs to IBV infection, we conducted a serological survey for U.S. Midwest domestic swine herds from 2010 to 2012. Results of this study showed that antibodies to IBVs were detected in 38.5% (20/52) of sampled farms, and 7.3% (41/560) of tested swine serum samples were positive for IBV antibodies. Furthermore, swine herds infected with porcine reproductive and respiratory syndrome virus (PRRSV) showed a higher prevalence of IBV antibodies in our 2014 survey. In addition, IBV was detected in 3 nasal swabs collected from PRRSV-seropositive pigs by real-time RT-PCR and sequencing. Finally, an experimental infection in pigs, via intranasal and intratracheal routes, was performed using one representative virus from each of the two genetically and antigenically distinct lineages of IBVs: B/Brisbane/60/2008 (Victoria lineage) and B/Yamagata/16/1988 (Yamagata lineage). Pigs developed influenza-like symptoms and lung lesions, and they seroconverted after virus inoculation. Pigs infected with B/Brisbane/60/2008 virus successfully transmitted the virus to sentinel animals. Taken together, our data demonstrate that pigs are susceptible to IBV infection; therefore, they warrant further surveillance and investigation of swine as a potential host for human IBV.

IMPORTANCE
IBV is an important human pathogen, but its ability to infect other species, for example, pigs, is not well understood. We showed serological evidence that antibodies to two genetically and antigenically distinct lineages of IBVs were present among domestic pigs, especially in swine herds previously infected with PRRSV, an immunosuppressive virus. IBV was detected in 3 nasal swabs from PRRSV-seropositive pigs by real-time reverse transcription-PCR and sequencing. Moreover, both lineages of IBV were able to infect pigs under experimental conditions, with transmissibility of influenza B/Victoria lineage virus among pigs being observed. Our results demonstrate that pigs are susceptible to IBV infections, indicating that IBV is a swine pathogen, and swine may serve as a natural reservoir of IBVs. In addition, pigs may serve as a model to study the mechanisms of transmission and pathogenesis of IBVs.
A Triple-Arginine Motif in the Amino-Terminal Domain and Oligomerization Are Required for HIV-1 Inhibition by Human MX2
Authors: Goujon Caroline , Greenbury Rebecca A. , Papaioannou Stelios , Doyle Tomas , Malim Michael H.
Published: February 2015

We have employed molecular genetic approaches to understand the domain organization of the HIV-1 resistance factor myxovirus resistance 2 (MX2). First, we describe an essential triple-arginine motif in the amino-terminal domain. Second, we demonstrate that this 91-residue domain mediates antiviral activity when appended to heterologous proteins, and we provide genetic evidence that protein oligomerization is required for MX2 function. These insights will facilitate future work aiming to elucidate MX2's mechanism of action.
Hepatitis C Virus Attenuates Mitochondrial Lipid β-Oxidation by Downregulating Mitochondrial Trifunctional-Protein Expression
Authors: Amako Yutaka , Munakata Tsubasa , Kohara Michinori , Siddiqui Aleem , Peers Chris , Harris Mark
Published: February 2015

The course of hepatitis C virus (HCV) infection and disease progression involves alterations in lipid metabolism, leading to symptoms such as hypocholesterolemia and steatosis. Steatosis can be induced by multiple mechanisms, including increases in lipid biosynthesis and uptake, impaired lipoprotein secretion, and/or attenuation of lipid β-oxidation. However, little is known about the effects of HCV on lipid β-oxidation. A previous proteomics study revealed that HCV interacted with both the α- and β-subunits of the mitochondrial trifunctional protein (MTP), an enzyme complex which catalyzes the last 3 steps of mitochondrial lipid β-oxidation for cellular energy production. Here we show that in HCV-infected Huh7.5 cells, lipid β-oxidation was significantly attenuated. Consistently with this, MTP protein and mRNA levels were suppressed by HCV infection. A loss-of-function study showed that MTP depletion rendered cells less responsive to alpha interferon (IFN-α) treatment by impairing IFN-stimulated gene expression. These aspects of host-virus interaction explain how HCV alters host energy homeostasis and how it may also contribute to the establishment of persistent infection in the liver.

IMPORTANCE
HCV infection triggers metabolic alterations, which lead to significant disease outcomes, such as fatty liver (steatosis). This study revealed that HCV impairs mitochondrial lipid β-oxidation, which results in low lipid combustion. On the other hand, the HCV-induced defects in metabolic status played an important role in the control of the type I interferon system. Under the conditions of impaired lipid β-oxidation, host cells were less responsive to the ability of exogenously added IFN-α to suppress HCV replication. This suggests that interference with lipid β-oxidation may assist the virus in the establishment of a long-term, persistent infection. Further understanding of this aspect of virus-host interaction may lead to improvements in the current standard therapy.
The Glycosylation Status of PrP
C
Is a Key Factor in Determining Transmissible Spongiform Encephalopathy Transmission between Species
Authors: Wiseman Frances K. , Cancellotti Enrico , Piccardo Pedro , Iremonger Kayleigh , Boyle Aileen , Brown Deborah , Ironside James W. , Manson Jean C. , Diack Abigail B.
Published: February 2015

The risk of transmission of transmissible spongiform encephalopathies (TSE) between different species has been notoriously unpredictable because the mechanisms of transmission are not fully understood. A transmission barrier between species often prevents infection of a new host with a TSE agent. Nonetheless, some TSE agents are able to cross this barrier and infect new species, with devastating consequences. The host PrP
C
misfolds during disease pathogenesis and has a major role in controlling the transmission of agents between species, but sequence compatibility between host and agent PrP
C
does not fully explain host susceptibility. PrP
C
is posttranslationally modified by the addition of glycan moieties which have an important role in the infectious process. Here, we show
in vivo
that glycosylation of the host PrP
C
has a significant impact on the transmission of TSE between different host species. We infected mice carrying different glycosylated forms of PrP
C
with two human agents (sCJDMM2 and vCJD) and one hamster strain (263K). The absence of glycosylation at both or the first PrP
C
glycosylation site in the host results in almost complete resistance to disease. The absence of the second site of N-glycan has a dramatic effect on the barrier to transmission between host species, facilitating the transmission of sCJDMM2 to a host normally resistant to this agent. These results highlight glycosylation of PrP
C
as a key factor in determining the transmission efficiency of TSEs between different species.

IMPORTANCE
The risks of transmission of TSE between different species are difficult to predict due to a lack of knowledge over the mechanisms of disease transmission; some strains of TSE are able to cross a species barrier, while others do not. The host protein, PrP
C
, plays a major role in disease transmission. PrP
C
undergoes posttranslational glycosylation, and the addition of these glycans may play a role in disease transmission. We infected mice that express different forms of glycosylated PrP
C
with three different TSE agents. We demonstrate that changing the glycosylation status of the host can have profound effects on disease transmission, changing host susceptibility and incubation times. Our results show that PrP
C
glycosylation is a key factor in determining risks of TSE transmission between species.
A Novel Rhabdovirus Isolated from the Straw-Colored Fruit Bat Eidolon helvum, with Signs of Antibodies in Swine and Humans
Authors: Binger Tabea , Annan Augustina , Drexler Jan Felix , Müller Marcel Alexander , Kallies René , Adankwah Ernest , Wollny Robert , Kopp Anne , Heidemann Hanna , Dei Dickson , Agya-Yao Festus Courage , Junglen Sandra , Feldt Torsten , Kurth Andreas , Oppong Samuel , Adu-Sarkodie Yaw , Drosten Christian
Published: February 2015

Bats have been implicated as reservoirs of emerging viruses. Bat species forming large social groups and roosting in proximity to human communities are of particular interest. In this study, we sampled a colony of ca. 350,000 individuals of the straw-colored fruit bat
Eidolon helvum
in Kumasi, the second largest city of Ghana. A novel rhabdovirus (Kumasi rhabdovirus [KRV]) was isolated in
E. helvum
cell cultures and passaged to Vero cells as well as interferon-competent human and primate cells (A549 and MA104). Genome composition was typical for a rhabdovirus. KRV was detected in 5.1% of 487 animals, showing association with the spleen but not the brain. Antibody prevalence was 11.5% by immunofluorescence and 6.4% by plaque reduction virus neutralization test (PRNT). Detection throughout 3 sampling years was pronounced in both annual wet seasons, of which only one overlaps the postparturition season. Juvenile bats showed increased viral prevalence. No evidence of infection was obtained in 1,240 female mosquitos (6 different genera) trapped in proximity to the colony to investigate potential vector association. Antibodies were found in 28.9% (5.4% by PRNT) of 107 swine sera but not in similarly large collections of sheep, goat, or cattle sera. The antibody detection rate in human subjects with occupational exposure to the bat colony was 11% (5/45 persons), which was significantly higher than in unexposed adults (0.8% [1/118]; chi square,
P
< 0.001). KRV is a novel bat-associated rhabdovirus potentially transmitted to humans and swine. Disease associations should be investigated.

IMPORTANCE
Bats are thought to carry a huge number of as-yet-undiscovered viruses that may pose epidemic threats to humans and livestock. Here we describe a novel dimarhabdovirus which we isolated from a large colony of the straw-colored fruit bat
Eidolon helvum
in Ghana. As these animals are exposed to humans and several livestock species, we looked for antibodies indicating infection in humans, cattle, swine, sheep, and goats. Signs of infection were found in swine and humans, with increased antibody findings in humans who are occupationally exposed to the bat colony. Our data suggest that it is worthwhile to look for diseases caused by the novel virus in humans and livestock.
A(H7N9) Virus Results in Early Induction of Proinflammatory Cytokine Responses in both Human Lung Epithelial and Endothelial Cells and Shows Increased Human Adaptation Compared with Avian H5N1 Virus
Authors: Zeng Hui , Belser Jessica A. , Goldsmith Cynthia S. , Gustin Kortney M. , Veguilla Vic , Katz Jacqueline M. , Tumpey Terrence M.
Published: February 2015

Similar to H5N1 viruses, A(H7N9) influenza viruses have been associated with severe respiratory disease and fatal outcomes in humans. While high viral load, hypercytokinemia, and pulmonary endothelial cell involvement are known to be hallmarks of H5N1 virus infection, the pathogenic mechanism of the A(H7N9) virus in humans is largely unknown. In this study, we assessed the ability of A(H7N9) virus to infect, replicate, and elicit innate immune responses in both human bronchial epithelial cells and pulmonary microvascular endothelial cells, compared with the abilities of seasonal H3N2, avian H7N9, and H5N1 viruses. In epithelial cells, A(H7N9) virus replicated efficiently but did not elicit robust induction of cytokines like that observed for H5N1 virus. In pulmonary endothelial cells, A(H7N9) virus efficiently initiated infection; however, no released infectious virus was detected. The magnitudes of induction of host cytokine responses were comparable between A(H7N9) and H5N1 virus infection. Additionally, we utilized differentiated human primary bronchial and tracheal epithelial cells to investigate cellular tropism using transmission electron microscopy and the impact of temperature on virus replication. Interestingly, A(H7N9) virus budded from the surfaces of both ciliated and mucin-secretory cells. Furthermore, A(H7N9) virus replicated to a significantly higher titer at 37°C than at 33°C, with improved replication capacity at 33°C compared to that of H5N1 virus. These findings suggest that a high viral load from lung epithelial cells coupled with induction of host responses in endothelial cells may contribute to the severe pulmonary disease observed following H7N9 virus infection. Improved adaptation of A(H7N9) virus to human upper airway poses an important threat to public health.

IMPORTANCE
A(H7N9) influenza viruses have caused over 450 documented human infections with a 30% fatality rate since early 2013. However, these novel viruses lack many molecular determinants previously identified with mammalian pathogenicity, necessitating a closer examination of how these viruses elicit host responses which could be detrimental. This study provides greater insight into the interaction of this virus with host lung epithelial cells and endothelial cells, which results in high viral load, epithelial cell death, and elevated immune response in the lungs, revealing the mechanism of pathogenesis and disease development among A(H7N9)-infected patients. In particular, we characterized the involvement of pulmonary endothelial cells, a cell type in the human lung accessible to influenza virus following damage of the epithelial monolayer, and its potential role in the development of severe pneumonia caused by A(H7N9) infection in humans.
Characterization of Herpes Simplex Virus 2 Primary MicroRNA Transcript Regulation
Authors: Tang Shuang , Bosch-Marce Marta , Patel Amita , Margolis Todd P. , Krause Philip R.
Published: February 2015

In order to understand factors that may influence latency-associated transcription and latency-associated transcript (LAT) phenotypes, we studied the expression of the herpes simplex virus 2 (HSV-2) LAT-associated microRNAs (miRNAs). We mapped the transcription initiation sites of all three primary miRNA transcripts and identified the ICP4-binding sequences at the transcription initiation sites of both HSV-2 LAT (pri-miRNA for miR-I and miR-II, which target ICP34.5, and miR-III, which targets ICP0) and L/ST (a pri-miRNA for miR-I and miR-II) but not at that of the primary miR-H6 (for which the target is unknown). We confirmed activity of the putative HSV-2 L/ST promoter and found that ICP4
trans
-activates the L/ST promoter when the ICP4-binding site at its transcription initiation site is mutated, suggesting that ICP4 may play a dual role in regulating transcription of L/ST and, consequently, of miR-I and miR-II. LAT exon 1 (containing LAT enhancer sequences), together with the LAT promoter region, comprises a bidirectional promoter required for the expression of both LAT-encoded miRNAs and miR-H6 in latently infected mouse ganglia. The ability of ICP4 to suppress ICP34.5-targeting miRNAs and to activate lytic viral genes suggests that ICP4 could play a key role in the switch between latency and reactivation.

IMPORTANCE
The HSV-2 LAT and viral miRNAs expressed in the LAT region are the most abundant viral transcripts during HSV latency. The balance between the expression of LAT and LAT-associated miRNAs and the expression of lytic viral transcripts from the opposite strand appears to influence whether individual HSV-infected neurons will be latently or productively infected. The outcome of neuronal infection may thus depend on regulation of gene expression of the corresponding primary miRNAs. In the present study, we characterize promoter sequences responsible for miRNA expression, including identification of the primary miRNA 5′ ends and evaluation of ICP4 response. These findings provide further insight into the virus' strategy to tightly control expression of lytic cycle genes (especially the neurovirulence factor, ICP34.5) and suggest a mechanism (via ICP4) for the transition from latency to reactivated productive infection.
The
MET
Gene Is a Common Integration Target in Avian Leukosis Virus Subgroup J-Induced Chicken Hemangiomas
Authors: Justice James , Malhotra Sanandan , Ruano Miguel , Li Yingying , Zavala Guillermo , Lee Nathan , Morgan Robin , Beemon Karen
Published: February 2015

Avian leukosis virus subgroup J (ALV-J) is a simple retrovirus that can cause hemangiomas and myeloid tumors in chickens and is currently a major economic problem in Asia. Here we characterize ALV-J strain PDRC-59831, a newly studied U.S. isolate of ALV-J. Five-day-old chicken embryos were infected with this virus, and the chickens developed myeloid leukosis and hemangiomas within 2 months after hatching. To investigate the mechanism of pathogenesis, we employed high-throughput sequencing to analyze proviral integration sites in these tumors. We found expanded clones with integrations in the
MET
gene in two of the five hemangiomas studied. This integration locus was not seen in previous work characterizing ALV-J-induced myeloid leukosis.
MET
is a known proto-oncogene that acts through a diverse set of signaling pathways and is involved in many neoplasms. We show that tumors harboring
MET
integrations exhibit strong overexpression of
MET
mRNA.

IMPORTANCE
These data suggest that ALV-J induces oncogenesis by insertional mutagenesis, and integrations in the
MET
oncogene can drive the overexpression of
MET
and contribute to the development of hemangiomas.
Structure and Receptor Binding Preferences of Recombinant Hemagglutinins from Avian and Human H6 and H10 Influenza A Virus Subtypes
Authors: Yang Hua , Carney Paul J. , Chang Jessie C. , Villanueva Julie M. , Stevens James
Published: February 2015

During 2013, three new avian influenza A virus subtypes, A(H7N9), A(H6N1), and A(H10N8), resulted in human infections. While the A(H7N9) virus resulted in a significant epidemic in China across 19 provinces and municipalities, both A(H6N1) and A(H10N8) viruses resulted in only a few human infections. This study focuses on the major surface glycoprotein hemagglutinins from both of these novel human viruses. The detailed structural and glycan microarray analyses presented here highlight the idea that both A(H6N1) and A(H10N8) virus hemagglutinins retain a strong avian receptor binding preference and thus currently pose a low risk for sustained human infections.

IMPORTANCE
Human infections with zoonotic influenza virus subtypes continue to be a great public health concern. We report detailed structural analysis and glycan microarray data for recombinant hemagglutinins from A(H6N1) and A(H10N8) viruses, isolated from human infections in 2013, and compare them with hemagglutinins of avian origin. This is the first structural report of an H6 hemagglutinin, and our results should further the understanding of these viruses and provide useful information to aid in the continuous surveillance of these zoonotic influenza viruses.
Endovascular treatment of jugular bulb diverticula causing debilitating pulsatile tinnitus
Authors: Mortimer Alex M , Harrington Tim , Steinfort Brendan , Faulder Ken
Published: February 2015

We describe the case of a patient who presented with debilitating pulsatile tinnitus in association with two jugular bulb diverticula. The diverticula were treated with stenting of the jugular bulb and coil embolization of the diverticula over two procedures. This resulted in successful resolution of symptoms and at 10 months follow-up the patient is asymptomatic. The technique is discussed with regard to similar published cases and surrogate measures of safety taken from the literature pertaining to idiopathic intracranial hypertension.
High renal regional oxygen saturation in femoral arteriovenous fistula after neonatal cardiac surgery
Authors: Tremblay-Roy Jean-Sébastien , Harrington Karen , Vobecky Suzanne , Emeriaud Guillaume
Published: February 2015

The use of an indwelling arterial catheter is standard practice in the postoperative monitoring of paediatric cardiac surgery patients. Arteriovenous fistula related to this procedure can be difficult to diagnose. Regional haemoglobin oxygen saturation (rSO2) using near-infrared spectroscopy and central venous oxygen saturation (ScvO2) are monitored to follow the balance between oxygen consumption and delivery. Low values of these parameters are a sign of low cardiac output. High rSO2and high ScvO2are less frequently described. We report the discovery of an iatrogenic arteriovenous fistula in a neonate after cardiac surgery who had unexpectedly high values of renal rSO2and femoral ScvO2. High renal rSO2after femoral instrumentation should alert the physician to the possibility of arteriovenous fistula.
Pulmonary leucostasis in a patient with chronic lymphocytic leukaemia
Authors: Awad Christina , Parikh Rajul , Fardous Yara
Published: February 2015

A 71-year-old woman with no chronic medical problems presented to the emergency room with a 24-month history of chronic non-productive cough, malaise, increasing fatigue and weight loss. On physical examination, she had significant cervical and axillary lymphadenopathy with no organomegaly. She was diagnosed with chronic lymphocytic leukaemia (CLL) due to her lymphocyte count of 1789.4×109/L on admission. A few days after hospitalisation, she developed respiratory failure requiring intubation. A chest X-ray showed interstitial markings. The abnormally high number of mature lymphocytes could have caused leucostasis in the lungs of this patient with CLL.
Retinal pseudoangiitis after intravitreal triamcinolone
Authors: García-Campos Jose Manuel , García-Basterra Ignacio , Kamal-Salah Radua , Baquero-Aranda Isabel
Published: February 2015

We present a case of a 40-year-old woman with a fundus image similar to frosted retinal angiitis after undergoing pars plana vitrectomy and intravitreal triamcinolone injection. The patient with diabetic retinopathy was referred to our hospital with vision loss in her right eye secondary to vitreous haemorrhage. After pars plana vitrectomy and injection of triamcinolone acetonide a funduscopy examination revealed deposits of triamcinolone along the retinal vessels simulating a frosted retinal angiitis. Triamcinolone deposits along blood vessels could be the result of the reabsorption process of these crystals by the perivascular macrophages. Further studies are needed.
A patient presenting with stress-induced epigastric pain
Authors: Duckheim Martin , Geisler Tobias , Zuern Christine Stefanie , Gawaz Meinrad
Published: February 2015

The median arcuate ligament passes the truncus coeliacus superior to its ostium. If it is thickened and located too low, it can cause external compression and stenosis of the truncus coeliacus, leading to postprandial abdominal pain and vomiting. This combination of symptoms is called median arcuate ligament syndrome. We report the case of a 79-year-old patient who suffered from chronic epigastric pain, which was initially assumed to be caused by either coronary artery disease or atherosclerotic stenosis of the coeliac artery. Angiography excluded coronary artery disease, but showed severe external stenosis of the truncus. The patient underwent laparoscopic release of the median arcuate ligament, which resulted in relief of his symptoms. The median arcuate ligament syndrome should be considered in patients with epigastric stress-induced pain. Further underlying pathologies, especially coronary artery disease, as life-threatening diagnosis have to be initially excluded.
The quality of hospital work environments and missed nursing care is linked to heart failure readmissions: a cross-sectional study of US hospitals
Authors: Brooks Carthon J Margo , Lasater Karen B , Sloane Douglas M , Kutney-Lee Ann
Published: February 2015

Introduction

Threats to quality and patient safety may exist when necessary nursing care is omitted. Empirical research is needed to determine how missed nursing care is associated with patient outcomes.

Aim

The aim of this study was to examine the relationship between missed nursing care and hospital readmissions.

Methods

Cross-sectional examination, using three linked data sources—(1) nurse survey, (2) patient discharge data from three states (California, New Jersey and Pennsylvania) and (3) administrative hospital data— from 2005 to 2006. We explored the incidence of 30-day readmission for 160 930 patients with heart failure in 419 acute care hospitals in the USA. Logistic regression was used to assess the effect of missed care on the odds of readmission, adjusting for patient and hospital characteristics.

Results

The most frequently missed nursing care activities across all hospitals in our sample included talking to and comforting patients (42.0%), developing and updating care plans (35.8%) and educating patients and families (31.5%). For 4 of the 10 studied care activities, each 10 percentage-point increase in the number of nurses reporting having missed the activity was associated with an increase in the odds of readmission by 2–8% after adjusting for patient and hospital characteristics. However, missed nursing care was no longer a significant predictor of readmission once adjusting for the nurse work environment, except in the case of the delivery of treatments and procedures (OR 1.08, 95% CI 1.02 to 1.14).

Conclusions

Missed care is an independent predictor of heart failure readmissions. However, once adjusting for the quality of the nurse work environment, this relationship is attenuated. Improvements in nurses’ working conditions may be one strategy to reduce care omissions and improve patient outcomes.
Improving the quality of discharge summaries for elective surgical procedures at North Bristol NHS Trust
Authors: Ladds Emma , Betteridge Frederica , Yamamoto Sarah , Gupta-Jessop Thomas
Published: February 2015

Following elective surgical procedures, hospital discharge summaries are essential in the handover to primary care. The information provided varies between institutions and is highly user-dependent. Various interventions have focused on improving information transfer to patients and primary care physicians including the development of electronic templates, electronic transmission to primary care, and training initiatives for junior doctors.

An evaluation of the urological patient’s journey at Southmead Hospital revealed a need for improved discharge summary advice. Urology specialists developed "gold standard" templates for elective urological procedures. Following a new rotation of junior doctors, discharge summaries were audited for one week. The templates were then made available on the urology ward, a teaching session was employed to encourage compliance, and the hospital electronic discharge summary template was edited. Following each intervention, summaries for one week of urology procedures were audited to assess the quality of advice provided to patients.

At baseline, 18% of discharge summaries contained sufficient patient advice, this reduced to 10% after templates were made available on the wards, increasing to 45% following the education session and 84% once the electronic discharge summary proforma was edited. We conclude that discharge summaries are an effective time point for intervening to provide patients with specific post-operative information and this may be optimised for different elective procedures via the introduction of electronically-distributed standardised templates.
Dilemmas of a rota: Google's solution
Authors: Qureshi Jibran S , Javaid Fatimah
Published: February 2015

Doctors take many forms of leave to further career training. Many hospital rotas omit these and are not updated frequently to reflect swaps in on-call duties. As a result, confusion arises with reduced staffing levels leading to sub-optimal patient care. Using Google Sheets, rota’s can be modified to be team specific, remotely accessed, and edited by any device with an internet connection and web browser. A qualitative pre and post-implementation questionnaire assessed the usefulness of the online rota.

The rota was trialled on a surgical and medical team containing foundation year, core medical, core surgical, and registrar trainees. The respective surgical and medical rotas were copied, modified and pasted into a Google Sheet to contain only team specific information including all forms of leave. A link was emailed allowing teams to access and edit the rota. Post-implementation questionnaire 90% (n=10) stated they could access it remotely and 100% felt the new rota was very easy to use. Finally, 80% stated the Google Doc rota was a definite improvement on the old trust rota.

The rota was then trialled on an ITU SHO rota (n=8). The results were reproducible with 88% feeling it addressed their requirements and stating it was an improvement on their old rota. As a result of the implementation appropriate staffing levels were maintained on the ward. The key advantages of the Google rota are that it included all forms of leave and helped ensure adequate staffing levels on the ward. The remote nature means easy access even if off-site and can be viewed easier on smart phones. The different privacy settings ensure security of document. The rota is updated in real-time giving an accurate representation of staffing levels – vital for service managers. The software is free to use, allowing it to work within current hospital IT framework.
Improving venous thromboembolism (VTE) prophylaxis in acute urological admissions during out of hours through the introduction of a urological admission proforma
Authors: Gerakopoulos Efstratios
Published: February 2015

Venous thromboembolism (VTE) kills more people than breast cancer, road traffic accidents, and AIDS combined, accounting for approximately 25,000 in-hospital deaths in England annually. The cost to the NHS is estimated at £640 million/annum. The most important element of VTE risk assessment strategy in England is to risk assess all patients for VTE on admission.

The aim of our quality improvement programme (QIP) was to monitor our practice regarding VTE prophylaxis of the patients' admitted urgently in our department, and then implement a measure to increase compliance if found to be poor. Our standards were based on the National Institute for Health and Care Excellence (NICE) guidelines which state that all urgently admitted patients must have a completed VTE assessment form within 24 hours of admission and receive appropriate VTE prophylaxis including low molecular weight heparin (LMWH) and/or TED stockings.

Our initial audit was conducted over a period of five weeks. All adult patients acutely admitted out of hours (5pm to 8am) were included. We then introduced a specially designed urological admissions proforma and organised several teaching sessions for junior doctors who facilitated acute admissions. Re-audit was performed using the same methods and timescale measuring improvement. Second re-audit six months after the introduction of the proforma, following the induction of the new cohort of junior doctors.

- Primary audit: n=44. Proportion of: completed VTE form=56%, LMWH appropriately prescribed=65%,TEDS=35%. VTE related complications=3

- 1st re-audit: n=42. Proportion of: completed VTE form=93%, LMWH appropriately prescribed=83%,TEDS=64%. VTE related complications=0

- 2nd re-audit:n=43. Proportion of: completed VTE form=92%, LMWH prescribed=84%, TEDS=76%. VTE related complications=1

There has been a significant increase of compliance with the NICE guidelines regarding VTE prophylaxis within our department through introducing the specially designed urological admissions proforma and delivering teaching sessions for junior doctors. The implementation of the proforma also led to decreased prevalence of VTE related complications and their subsequent morbidity and mortality.