bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating the overlap of obstructive lung disease and obstructive sleep apnoea: OLDOSA syndrome
Authors: Ioachimescu Octavian C. , Teodorescu Mihaela
Published: January 2013

Obstructive lung diseases (OLD) such as asthma and chronic obstructive pulmonary disease (COPD) are very prevalent conditions. Disease phenotypes (e.g. chronic bronchitis, emphysema, etc.) often overlap, and significant confusion exists about their optimal nosologic characterization. Obstructive sleep apnoea (OSA) is also a common condition that features bidirectional interactions with OLD. OSA appears to be more commonly seen in patients with OLD, perhaps as a result of shared risk factors, for example obesity, smoking, increased airway resistance, local and systemic inflammation, anti‐inflammatory therapy. Conversely, OSA is associated with worse clinical outcomes in patients with OLD, and continuous positive airway pressure therapy has potential beneficial effects on this vicious pathophysiological interaction. Possible shared mechanistic links include increased parasympathetic tone, hypoxaemia‐related reflex bronchoconstriction/vasoconstriction, irritation of upper airway neural receptors, altered nocturnal neurohormonal secretion, pro‐inflammatory mediators, within and inter‐breath interactions between upper and lower airways, lung volume‐airway dependence, etc. While the term overlap syndrome has been defined as the comorbid association of COPD and OSA, the interaction between asthma and OSA has not been integrated yet nosologically; in this review, the latter will be called alternative overlap syndrome. In an effort to bolster further investigations in this area, an integrated, lumping nomenclature for OSA in the setting of OLD is proposed here—OLDOSA (obstructive lung disease and obstructive sleep apnoea) syndrome.
European guidelines for prevention and management of influenza in hematopoietic stem cell transplantation and leukemia patients: summary of ECIL‐4 (2011), on behalf of ECIL, a joint venture of EBMT, EORTC, ICHS, and ELN
Authors: Engelhard D. , Mohty B. , de la Camara R. , Cordonnier C. , Ljungman P.
Published: January 2013

Influenza may cause severe disease and mortality in leukemia patients and in hematopoietic stem cell transplantation recipients. The 4th European Conference of Infections in Leukemia (ECIL‐4) has developed evidence‐based guidelines for prevention and management of influenza infections in these patients. Real‐time reverse‐transcription polymerase chain reaction is the diagnostic test of choice, as it is the most sensitive and specific test for influenza. The risks for severe influenza and fatal outcome include lymphopenia, older age, influenza soon after transplantation or chemotherapy, steroid treatment, and lack of early antiviral therapy. Neuraminidase inhibitors (oral oseltamivir or inhalation of zanamivir) are currently the most effective therapeutic agents for influenza. Main preventive measures include annual vaccination of patients, household contacts, and hospital staff. This review summarizes ECIL‐4's main recommendations.
Results of phenol red thread test in clinically normal Syrian hamsters (Mesocricetus auratus)
Authors: Rajaei Seyed Mehdi , Sadjadi Reza , Sabzevari Amin , Ghaffari M. Selk
Published: January 2013

Objective

To determine the normal reference range for phenol red thread test (PRTT) values in clinically normal Syrian hamsters (Mesocricetus auratus).

Animals

Sixteen healthy adult Syrian hamsters (eight males and eight females) were used in this study.

Procedure

Ophthalmic examinations were performed without chemical restraint. PRTT values were evaluated in both eyes of all Syrian hamsters using a commercial PRTT strip of a single lot number.

Results

No statistically significant differences between right and left eyes were found for any of the results. The mean ± SD PRTT values for the study population were 6.8 ± 2.5 mm/15 s with a range from 3 to 11.5 mm/15 s. Mean PRTTs in male animals were 5.1 ± 1.2 mm/15 s, whereas mean PRTTs in female hamsters were 8.5 ± 2.3 mm/15 s. Comparison between mean PRTT values in males and females showed a significant difference (P = 0.004). Mean weights for males and females were 80.9 ± 4.8 and 90.6 ± 8.5 g, respectively. No linear relationship between mean PRTT and body weight was found in female (P = 0.46) and male (P = 0.92) hamsters.

Conclusion

This study provides novel data for normal reference ranges of PRTT values in healthy Syrian hamsters. Results of this study may assist veterinarians in the diagnosis of ocular surface disease and syndromes affecting the tear film in these species.
Wave Propagation in Rapid Granular Flows
Authors: Ahn Hojin
Published: January 2013

One-dimensional wave propagation in granular flow has been investigated using a three-dimensional discrete element model (DEM). Cohesionless, dry, smooth, elastic, hard spheres are randomly distributed in a cylinder-piston system with initial granular temperature and solid fraction. Upon a sudden motion of the piston, subsequent wave propagation in granular materials between two ends of the cylinder is numerically simulated. The simulation results of wave speed normalized by the square root of granular temperature are found to be well correlated as a function of solid fraction. Comparison with several analytical works in the literature shows that the simulated wave speed is in good agreement with the wave speed calculated at the isentropic condition but is higher than that at the constant granular temperature condition. Finally the simulation result is employed to describe shock waves observed in the literature. It has been found that, when particles rapidly flow through an orifice, a shock is formed very near the location of the maximum granular temperature. It has also been observed that a shock can be formed even when the flow does not appear to be choked due to its low density upstream of the orifice.
Temperature dependence of the resistive switching-related currents in ultra-thin high-k based MOSFETs
Authors: Crespo-Yepes Albert , Martin-Martinez Javier , Rodriguez Rosana , Nafria Montse , Aymerich Xavier
Published: January 2013

In this work, the temperature dependence of the resistive switching phenomenon in metal-oxide-semiconductor field-effect-transistor (MOSFETs) with an ultra-thin Hf-based high-k dielectric is studied through analysis of the gate and drain currents for the two dielectric conductivity states. These two different conductive states of the resistive switching have been associated with the dielectric breakdown (BD) and dielectric BD reversibility (R), respectively, and are related to the creation of a BD path through the dielectric that can be understood as a conductive filament. The results of the temperature dependence of the post-BD gate current are in agreement with those obtained from the study of the injected charge to recovery, which is a useful parameter with which to analyze the switch from the high to low conductivity state. The drain current in the MOSFETs for the two conductivity states, for different locations of the BD path along the channel (close to the source and close to the drain), and at several temperatures has also been studied. The results contribute to a better understanding of the resistive switching phenomenon in ultra-thin gate dielectrics. This contribution could be useful for the developing of models to describe BD reversibility.
Graphene-capped InAs/GaAs quantum dots
Authors: Ajlani Hosni , Othmen Riadh , Oueslati Meherzi , Cavanna Antonnella , Madouri Ali
Published: January 2013

Graphene was grown by chemical vapor deposition and successfully transferred onto InAs/GaAs quantum dots (QDs) grown by molecular beam epitaxy on a (001) GaAs substrate. To our knowledge, the hybrid structure of graphene replacing the conventional GaAs layer as a cap layer has not been explored until now. In this work, the authors present the photoluminescence (PL) and Raman spectroscopy study of InAs/GaAs graphene-capped QDs. The Raman measurements show an intense 2D peak at 2704 cm−1 which is the main characteristic indicating the presence of graphene. The recorded PL at temperature T = 300 K shows two sharp peaks located at 1.177 and 1.191 eV, which is attributed to radiative emission from the quantum dots. These peaks, which are generally very weak in InAs/GaAs quantum dots at this temperature, are instead very intense. The enhancement of the PL emission evidenced electron transfer from the graphene layer to the QDs.
Recent Changes in the Ventilation of the Southern Oceans
Authors: Waugh Darryn W. , Primeau Francois , DeVries Tim , Holzer Mark
Published: January 2013

The Change of Winds

As the combined effects of Antarctic stratospheric ozone depletion and climate warming have forced the westerly surface winds in the Southern Hemisphere to shift toward the pole, mixing between the upper ocean and deeper waters has also changed.

Waugh
et al.

(p.
568
) now show that water originating at the surface at subtropical latitudes is mixing into the deeper ocean at a higher rate than 20 years ago, while the reverse is true for those originating at higher latitudes. The summer westerly winds that blow in the Southern Hemisphere have shifted toward the South Pole over the past several decades, but why?
Lee and Feldstein
(p.
563
) show that greenhouse gas forcing and ozone depletion impart different signatures to wind patterns and conclude that ozone depletion has been responsible for more than half of the observed shift.
Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition
Authors: Yu Min , Bardia Aditya , Wittner Ben S. , Stott Shannon L. , Smas Malgorzata E. , Ting David T. , Isakoff Steven J. , Ciciliano Jordan C. , Wells Marissa N. , Shah Ajay M. , Concannon Kyle F. , Donaldson Maria C. , Sequist Lecia V. , Brachtel Elena , Sgroi Dennis , Baselga Jose , Ramaswamy Sridhar , Toner Mehmet , Haber Daniel A. , Maheswaran Shyamala
Published: January 2013

Cells in Transit(ion)

Epithelial-mesenchymal transition (EMT) is a developmental program that converts adherent epithelial cells to a migratory mesenchymal state. This cell-fate change has been linked to tumor metastasis in preclinical models. To investigate whether EMT occurs in human cancer,Yuet al.(p.580) isolated circulating tumor cells (CTCs) from breast cancer patients and analyzed their expression of epithelial and mesenchymal markers by RNA–in situ hybridization and RNA sequencing. Biphenotypic cells expressing both types of markers were rare in primary breast tumors but were enriched among CTCs, as were cells expressing only mesenchymal markers. Serial blood samples from one patient revealed that CTCs in the mesenchymal state declined in number when the patient responded to therapy but rebounded when the disease began to progress—a pattern repeated when a different therapy was administered. Thus, EMT may facilitate tumor cell dissemination in humans.
Uncovering the Protein Translocon at the Chloroplast Inner Envelope Membrane
Authors: Kikuchi Shingo , Bédard Jocelyn , Hirano Minako , Hirabayashi Yoshino , Oishi Maya , Imai Midori , Takase Mai , Ide Toru , Nakai Masato
Published: January 2013

Chloroplast Translocon Revealed

Protein translocation across biological membranes requires supramolecular complexes, called translocons. Chloroplasts require translocons in their double-envelope membranes to import thousands of nucleus-encoded proteins synthesized in the cytosol. However, the identity of the translocon at the inner envelope of the chloroplast (TIC) has long been a matter of debate; two proteins, Tic20 and Tic110, have been proposed to be central to protein translocation across the inner envelope membrane. Using transgenic
Arabidopsis
plants expressing a tagged form of Tic20,

Kikuchi
et al.

(p.
571
) report the isolation of a 1-megadalton complex composed of Tic56, Tic100, and Tic214 involved in protein translocation across the inner envelope. Thorough in vitro biochemical and in vivo genetic experimentation suggest that the isolated translocon contains both nuclear- and organellar-encoded components. Tic110 was not part of the isolated translocon.
Authigenic Carbonate and the History of the Global Carbon Cycle
Authors: Schrag Daniel P. , Higgins John. A. , Macdonald Francis A. , Johnston David T.
Published: January 2013

The Third Way

Because organic carbon contains a larger fraction of the light isotope
12
C than inorganic carbonate, variations in the carbon isotopic record of sedimentary rocks are thought to represent changes in the amount of organic carbon buried as sediments (and thus removed from the rest of the carbon cycle).

Schrag
et al.

(p.
540
; see the Perspective by

Canfield and Kump

) suggest that historically a third component was important: authigenic carbonate. Authigenic carbonate is not produced in any appreciable quantity today, but was much more abundant when the level of atmospheric oxygen was low.
Systematic Identification of Signal-Activated Stochastic Gene Regulation
Authors: Neuert Gregor , Munsky Brian , Tan Rui Zhen , Teytelman Leonid , Khammash Mustafa , van Oudenaarden Alexander
Published: January 2013

Modeling Stress

Much is known about various factors (transcription and epigenetic factors) involved in gene transcription, but it is difficult to predict expression at a quantitative level.

Neuert
et al.

(p.
584
) developed an integrated experimental and computational procedure to capture, predict, and understand the temporal dynamics of signal-activated gene regulation at single-molecule and single-cell resolution. The approach explores models of varying complexity and uses cross-validation analyses to estimate when models are too simple to be accurate or too complex to be precise. These approaches identify and validate a model that describes and predicts the quantitative messenger RNA dynamics of three genes activated by mitogen-activated protein kinase signaling during cellular stress in yeast.
The Psst That Pierced the Sky Is Now Churning the Sea
Authors: Kerr Richard A.
Published: January 2013

Once miraculous, chlorofluorocarbons that caused ozone damage are now helping scientists track its effects on the Southern Ocean.
Tight Budgets Squeeze European Earth Observation
Authors: Clery Daniel
Published: January 2013

The Europe-wide financial crisis and uncertainty over the European Union's future funding are casting shadows over Earth monitoring and science missions.
Outer Surface Protein C Peptide Derived from Borrelia burgdorferi Sensu Stricto as a Target for Serodiagnosis of Early Lyme Disease
Authors: Arnaboldi Paul M. , Seedarnee Rudra , Sambir Mariya , Callister Steven M. , Imparato Josephine A. , Dattwyler Raymond J.
Published: January 2013

Current serodiagnostic assays for Lyme disease are inadequate at detecting early infection due to poor sensitivity and nonspecificity that arise from the use of whole bacteria or bacterial proteins as assay targets; both targets contain epitopes that are cross-reactive with epitopes found in antigens of other bacterial species. Tests utilizing peptides that contain individual epitopes highly specific for
Borrelia burgdorferi
as diagnostic targets are an attractive alternative to current assays. Using an overlapping peptide library, we mapped linear epitopes in OspC, a critical virulence factor of
B. burgdorferi
required for mammalian infection, and confirmed the results by enzyme-linked immunosorbent assay (ELISA). We identified a highly conserved 20-amino-acid peptide epitope, OspC1. Via ELISA, OspC1 detected specific IgM and/or IgG in 60 of 98 serum samples (62.1%) obtained from patients with erythema migrans (early Lyme disease) at the time of their initial presentation. By comparison, the commercially available OspC peptide PepC10 detected antibody in only 48 of 98 serum samples (49.0%). In addition, OspC1 generated fewer false-positive results among negative healthy and diseased (rheumatoid arthritis and positive Rapid Plasma Reagin [RPR+] test result) control populations than did PepC10. Both highly specific and more sensitive than currently available OspC peptides, OspC1 could have value as a component of a multipeptide Lyme disease serological assay with significantly improved capabilities for the diagnosis of early infection.
Identification of Allergenic Component Tyr p 8 from Tyrophagus putrescentiae and Cross-Reactivity with Der p 8
Authors: Liao En-Chih , Lin Yi-Hsueh , Chiu Chih-Liang , Lin Ting-Chu , Tsai Jaw-Ji
Published: January 2013

Group 8 mite allergens exhibit sequence homology to glutathione
S
-transferases (GSTs), such as that from
Dermatophagoides pteronyssinus
(Der p 8). GSTs have been identified as important allergens in studies of allergens from house dust mites, cockroaches, and fungi. Our objective was to purify the native group 8 allergen from
Tyrophagus putrescentiae
(nTyr p 8) and generate recombinant Tyr p 8 (rTyr p 8) for immunological characterization. The allergenicity was determined by antibody recognition, IgE inhibition, and triggering of the basophil-sensitized release of histamine, using
T. putrescentiae
hypersensitivity sera. The results showed that the mRNA transcript of nTyr p 8 is 657 bp long, contains 218 amino acids with a molecular mass of 26 kDa, and exhibits 83% sequence homology to Der p 8. Serum samples from the allergic patients with an IgE-positive response to
T. putrescentiae
were analyzed to determine their IgE response to rTyr p 8. The results showed that the sera of 48 subjects (45.3%) had specific IgE against rTyr p 8. However, sera of only 19 subjects (17.9%) had specific IgE against rTyr p 8 after
D. pteronyssinus
absorption. Histamine release was observed from
T. putrescentiae
-allergic subjects in the presence of rTyr p 8. Both the nTyr p 8 and
T. putrescentiae
crude extract had been demonstrated to possess GST enzymatic activity. Although the specific binding of serum IgE to rTyr p 8 was only 17.9%, which indicates that rTyr p 8 was not a major allergen, the positive response to rTyr p 8 was due to the cross-reactivity with Der p 8. The group 8 mite allergen might be of use in the design of a suitable allergen for diagnosis and for the development of novel immunotherapies.
Complete Genome Sequence of a Rabies Virus Isolate from Cattle in Guangxi, Southern China
Authors: Tang Hai-Bo , He Xiao-Xia , Zhong Yi-Zhi , Liao Su-Huan , Zhong Tao-Zhen , Xie Lin-Juan , Pan Yan , Lu Zhuan-Ling , Wei Xian-Kai , Luo Yang , Luo Ting Rong
Published: February 2013

A street rabies virus (RV) isolate, GXHXN, was obtained from brain tissue of rabid cattle in the Guangxi Zhuang Autonomous Region of China in 2009. GXHXN is the first isolate from cattle in China with its entire genome sequenced and is closely related to BJ2011E from horse in Beijing, WH11 from donkey in the Hubei Province, and isolates from dogs in the Guangxi and Fujian Provinces, with homologies of 97.6% to 99.6%. It is more distantly related to isolates from domestic cat, pig, Chinese ferret badger, and vaccine strains, with homologies of 83.1% to 88.0%.
Identification of Endogenous Coccidioides posadasii Contamination of Commercial Primary Rhesus Monkey Kidney Cells
Authors: Ginocchio Christine C. , Lotlikar Madhavi , Li Xiaojiang , Elsayed Hoda H. , Teng Yu , Dougherty Pamela , Kuhles Daniel J. , Chaturvedi Sudha , St. George Kirsten
Published: January 2013

Here we describe the identification of endogenous
Coccidioides posadasii
contamination in commercial rhesus monkey kidney (RhMK) cells and the subsequent nationwide alert that reduced the risk of laboratory exposure. This extraordinary event highlights the necessity for laboratories to remain vigilant in the use of appropriate biosafety procedures, particularly when working with unknown pathogens.
A Human Papilloma Virus Testing Algorithm Comprising a Combination of the L1 Broad-Spectrum SPF
10
PCR Assay and a Novel E6 High-Risk Multiplex Type-Specific Genotyping PCR Assay
Authors: van Alewijk Dirk , Kleter Bernhard , Vent Maarten , Delroisse Jean-Marc , de Koning Maurits , van Doorn Leen-Jan , Quint Wim , Colau Brigitte
Published: January 2013

Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detection and genotyping systems. To improve HPV detection by PCR, the broad-spectrum L1-based SPF
10
PCR DNA enzyme immunoassay (DEIA) LiPA system and a novel E6-based multiplex type-specific system (MPTS123) that uses Luminex xMAP technology were combined into a new testing algorithm. To evaluate this algorithm, cervical swabs (
n
= 860) and cervical biopsy specimens (
n
= 355) were tested, with a focus on HPV types detected by the MPTS123 assay (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 6, and 11). Among the HPV-positive samples, identifications of individual HPV genotypes were compared. When all MPTS123 targeted genotypes were considered together, good overall agreement was found (κ = 0.801, 95% confidence interval [CI], 0.784 to 0.818) with identification by SPF
10
LiPA, but significantly more genotypes (
P
< 0.0001) were identified by the MPTS123 PCR Luminex assay, especially for HPV types 16, 35, 39, 45, 58, and 59. An alternative type-specific assay was evaluated that is based on detection of a limited number of HPV genotypes by type-specific PCR and a reverse hybridization assay (MPTS12 RHA). This assay showed results similar to those of the expanded MPTS123 Luminex assay. These results confirm the fact that broad-spectrum PCRs are hampered by type competition when multiple HPV genotypes are present in the same sample. Therefore, a testing algorithm combining the broad-spectrum PCR and a range of type-specific PCRs can offer a highly accurate method for the analysis of HPV infections and diminish the rate of false-negative results and may be particularly useful for epidemiological and vaccine studies.
CHROMagar Orientation Medium Reduces Urine Culture Workload
Authors: Manickam Kanchana , Karlowsky James A. , Adam Heather , Lagacé-Wiens Philippe R. S. , Rendina Assunta , Pang Paulette , Murray Brenda-Lee , Alfa Michelle J.
Published: January 2013

Microbiology laboratories continually strive to streamline and improve their urine culture algorithms because of the high volumes of urine specimens they receive and the modest numbers of those specimens that are ultimately considered clinically significant. In the current study, we quantitatively measured the impact of the introduction of CHROMagar Orientation (CO) medium into routine use in two hospital laboratories and compared it to conventional culture on blood and MacConkey agars. Based on data extracted from our Laboratory Information System from 2006 to 2011, the use of CO medium resulted in a 28% reduction in workload for additional procedures such as Gram stains, subcultures, identification panels, agglutination tests, and biochemical tests. The average number of workload units (one workload unit equals 1 min of hands-on labor) per urine specimen was significantly reduced (
P
< 0.0001; 95% confidence interval [CI], 0.5326 to 1.047) from 2.67 in 2006 (preimplementation of CO medium) to 1.88 in 2011 (postimplementation of CO medium). We conclude that the use of CO medium streamlined the urine culture process and increased bench throughput by reducing both workload and turnaround time in our laboratories.
The Value of Combining Blood Culture and SeptiFast Data for Predicting Complicated Bloodstream Infections Caused by Gram-Positive Bacteria or Candida Species
Authors: Fernández-Cruz Ana , Marín Mercedes , Kestler Martha , Alcalá Luis , Rodriguez-Créixems Marta , Bouza Emilio
Published: January 2013

Management of complicated bloodstream infections requires more aggressive treatment than uncomplicated bloodstream infections. We assessed the value of follow-up blood culture in bloodstream infections caused by
Staphylococcus aureus
,
Enterococcus
spp.,
Streptococcus
spp., and
Candida
spp. and studied the value of persistence of DNA in blood (using SeptiFast) for predicting complicated bloodstream infections. Patients with bloodstream infections caused by these microorganisms were enrolled prospectively. After the first positive blood culture, samples were obtained every third day to perform blood culture and SeptiFast analyses simultaneously. Patients were followed to detect complicated bloodstream infection. The study sample comprised 119 patients. One-third of the patients developed complicated bloodstream infections. The values of persistently positive tests to predict complicated bloodstream infections were as follows: SeptiFast positive samples (sensitivity, 56%; specificity, 79.5%; positive predictive value, 54%; negative predictive value, 80.5%; accuracy, 72.3%) and positive blood cultures (sensitivity, 30.5%; specificity, 92.8%; positive predictive value, 64%; negative predictive value, 75.5%; accuracy, 73.9%). Multivariate analysis showed that patients with a positive SeptiFast result between days 3 and 7 had an almost 8-fold-higher risk of developing a complicated bloodstream infection. In
S. aureus
, the combination of both techniques to exclude endovascular complications was significantly better than the use of blood culture alone. We obtained a score with variables selected by the multivariate model. With a cutoff of 7, the negative predictive value for complicated bloodstream infection was 96.6%. Patients with a positive SeptiFast result between days 3 and 7 after a positive blood culture have an almost 8-fold-higher risk of developing complicated bloodstream infections. A score combining clinical data with the SeptiFast result may improve the exclusion of complicated bloodstream infections.
Comparative Study of IS
6110
Restriction Fragment Length Polymorphism and Variable-Number Tandem-Repeat Typing of Mycobacterium tuberculosis Isolates in the Netherlands, Based on a 5-Year Nationwide Survey
Authors: de Beer Jessica L. , van Ingen Jakko , de Vries Gerard , Erkens Connie , Sebek Maruschka , Mulder Arnout , Sloot Rosa , van den Brandt Anne-Marie , Enaimi Mimount , Kremer Kristin , Supply Philip , van Soolingen Dick
Published: January 2013

In order to switch from IS
6110
and polymorphic GC-rich repetitive sequence (PGRS) restriction fragment length polymorphism (RFLP) to 24-locus variable-number tandem-repeat (VNTR) typing of
Mycobacterium tuberculosis
complex isolates in the national tuberculosis control program in The Netherlands, a detailed evaluation on discriminatory power and agreement with findings in a cluster investigation was performed on 3,975 tuberculosis cases during the period of 2004 to 2008. The level of discrimination of the two typing methods did not differ substantially: RFLP typing yielded 2,733 distinct patterns compared to 2,607 in VNTR typing. The global concordance, defined as isolates labeled unique or identically distributed in clusters by both methods, amounted to 78.5% (
n
= 3,123). Of the remaining 855 cases, 12% (
n
= 479) of the cases were clustered only by VNTR, 7.7% (
n
= 305) only by RFLP typing, and 1.8% (
n
= 71) revealed different cluster compositions in the two approaches. A cluster investigation was performed for 87% (
n
= 1,462) of the cases clustered by RFLP. For the 740 cases with confirmed or presumed epidemiological links, 92% were concordant with VNTR typing. In contrast, only 64% of the 722 cases without an epidemiological link but clustered by RFLP typing were also clustered by VNTR typing. We conclude that VNTR typing has a discriminatory power equal to IS
6110
RFLP typing but is in better agreement with findings in a cluster investigation performed on an RFLP-clustering-based cluster investigation. Both aspects make VNTR typing a suitable method for tuberculosis surveillance systems.
Clinical Characteristics of Ochrobactrum anthropi Bacteremia
Authors: Hagiya Hideharu , Ohnishi Kouhei , Maki Miyako , Watanabe Naoto , Murase Tomoko
Published: January 2013

The clinical picture of
Ochrobactrum anthropi
infection is not well described because the infection is rare in humans and identification of the pathogen is difficult. We present a case of
O. anthropi
bacteremia that was initially misidentified as
Ralstonia paucula
and later identified by 16S rRNA sequencing and
recA
analysis.
Contrasting Roles of Mitogen-Activated Protein Kinases in Cellular Entry and Replication of Hepatitis C Virus: MKNK1 Facilitates Cell Entry
Authors: Kim Seungtaek , Ishida Hisashi , Yamane Daisuke , Yi MinKyung , Swinney David C. , Foung Steven , Lemon Stanley M.
Published: January 2013

The human kinome comprises over 800 individual kinases. These contribute in multiple ways to regulation of cellular metabolism and may have direct and indirect effects on virus replication. Kinases are tempting therapeutic targets for drug development, but achieving sufficient specificity is often a challenge for chemical inhibitors. While using inhibitors to assess whether c-Jun N-terminal (JNK) kinases regulate hepatitis C virus (HCV) replication, we encountered unexpected off-target effects that led us to discover a role for a mitogen-activated protein kinase (MAPK)-related kinase, MAPK interacting serine/threonine kinase 1 (MKNK1), in viral entry. Two JNK inhibitors, AS601245 and SP600125, as well as RNA interference (RNAi)-mediated knockdown of JNK1 and JNK2, enhanced replication of HCV replicon RNAs as well as infectious genome-length RNA transfected into Huh-7 cells. JNK knockdown also enhanced replication following infection with cell-free virus, suggesting that JNK actively restricts HCV replication. Despite this, AS601245 and SP600125 both inhibited viral entry. Screening of a panel of inhibitors targeting kinases that may be modulated by off-target effects of AS601245 and SP600125 led us to identify MKNK1 as a host factor involved in HCV entry. Chemical inhibition or siRNA knockdown of MKNK1 significantly impaired entry of genotype 1a HCV and HCV-pseudotyped lentiviral particles (HCVpp) in Huh-7 cells but had only minimal impact on viral RNA replication or cell proliferation and viability. We propose a model by which MKNK1 acts to facilitate viral entry downstream of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK), both of which have been implicated in the entry process.
Crystal Structure of a Poxvirus-Like Zalpha Domain from Cyprinid Herpesvirus 3
Authors: Tomé Ana Rita , Kuś Krzysztof , Correia Silvia , Paulo Lara Martins , Zacarias Sónia , de Rosa Matteo , Figueiredo Delio , Parkhouse R. Michael E. , Athanasiadis Alekos
Published: January 2013

Zalpha domains are a subfamily of the winged helix-turn-helix domains sharing the unique ability to recognize CpG repeats in the left-handed Z-DNA conformation. In vertebrates, domains of this family are found exclusively in proteins that detect foreign nucleic acids and activate components of the antiviral interferon response. Moreover, poxviruses encode the Zalpha domain-containing protein E3L, a well-studied and potent inhibitor of interferon response. Here we describe a herpesvirus Zalpha-domain-containing protein (ORF112) from cyprinid herpesvirus 3. We demonstrate that ORF112 also binds CpG repeats in the left-handed conformation, and moreover, its structure at 1.75 Å reveals the Zalpha fold found in ADAR1, DAI, PKZ, and E3L. Unlike other Zalpha domains, however, ORF112 forms a dimer through a unique domain-swapping mechanism. Thus, ORF112 may be considered a new member of the Z-domain family having DNA binding properties similar to those of the poxvirus E3L inhibitor of interferon response.
Venezuelan Equine Encephalitis Virus nsP2 Protein Regulates Packaging of the Viral Genome into Infectious Virions
Authors: Kim Dal Young , Atasheva Svetlana , Frolova Elena I. , Frolov Ilya
Published: January 2013

Alphaviruses are one of the most geographically widespread and yet often neglected group of human and animal pathogens. They are capable of replicating in a wide variety of cells of both vertebrate and insect origin and are widely used for the expression of heterologous genetic information both
in vivo
and
in vitro
. In spite of their use in a range of research applications and their recognition as a public health threat, the biology of alphaviruses is insufficiently understood. In this study, we examined the evolution process of one of the alphaviruses, Venezuelan equine encephalitis virus (VEEV), to understand its adaptation mechanism to the inefficient packaging of the viral genome in response to serial mutations introduced into the capsid protein. The new data derived from this study suggest that strong alterations in the ability of capsid protein to package the viral genome leads to accumulation of adaptive mutations, not only in the capsid-specific helix I but also in the nonstructural protein nsP2. The nsP2-specific mutations were detected in the protease domain and in the amino terminus of the protein, which was previously proposed to function as a protease cofactor. These mutations increased infectious virus titers, demonstrated a strong positive impact on viral RNA replication, mediated the development of a more cytopathic phenotype, and made viruses capable of developing a spreading infection. The results suggest not only that packaging of the alphavirus genome is determined by the presence of packaging signals in the RNA and positively charged amino acids in the capsid protein but also that nsP2 is either directly or indirectly involved in the RNA encapsidation process.
Frequent and Variable Cytotoxic-T-Lymphocyte Escape-Associated Fitness Costs in the Human Immunodeficiency Virus Type 1 Subtype B Gag Proteins
Authors: Boutwell Christian L. , Carlson Jonathan M. , Lin Tien-Ho , Seese Aaron , Power Karen A. , Peng Jian , Tang Yanhua , Brumme Zabrina L. , Heckerman David , Schneidewind Arne , Allen Todd M.
Published: January 2013

Cytotoxic-T-lymphocyte (CTL) escape mutations undermine the durability of effective human immunodeficiency virus type 1 (HIV-1)-specific CD8
+
T cell responses. The rate of CTL escape from a given response is largely governed by the net of all escape-associated viral fitness costs and benefits. The observation that CTL escape mutations can carry an associated fitness cost in terms of reduced virus replication capacity (RC) suggests a fitness cost-benefit trade-off that could delay CTL escape and thereby prolong CD8 response effectiveness. However, our understanding of this potential fitness trade-off is limited by the small number of CTL escape mutations for which a fitness cost has been quantified. Here, we quantified the fitness cost of the 29 most common HIV-1B Gag CTL escape mutations using an
in vitro
RC assay. The majority (20/29) of mutations reduced RC by more than the benchmark M184V antiretroviral drug resistance mutation, with impacts ranging from 8% to 69%. Notably, the reduction in RC was significantly greater for CTL escape mutations associated with protective HLA class I alleles than for those associated with nonprotective alleles. To speed the future evaluation of CTL escape costs, we also developed an
in silico
approach for inferring the relative impact of a mutation on RC based on its computed impact on protein thermodynamic stability. These data illustrate that the magnitude of CTL escape-associated fitness costs, and thus the barrier to CTL escape, varies widely even in the conserved Gag proteins and suggest that differential escape costs may contribute to the relative efficacy of CD8 responses.
Tyrosine Phosphorylation of the Triple Gene Block Protein 3 Regulates Cell-to-Cell Movement and Protein Interactions of Potato Mop-Top Virus
Authors: Samuilova Olga , Santala Johanna , Valkonen Jari P. T.
Published: January 2013

Functions of viral proteins can be regulated through phosphorylation by serine/threonine kinases in plants, but little is known about the involvement of tyrosine kinases in plant virus infection. In this study, TGBp3, one of the three movement proteins encoded by a triple gene block (TGB) of
Potato mop-top virus
(PMTV), was detected for the first time in PMTV-infected plants and found to be tyrosine phosphorylated. Phosphorylation sites (Tyr
87–89
and Tyr
120
) were located in two amino acid motifs conserved in the TGB-containing, rod-shaped plant viruses. Substitution of these tyrosine residues in both motifs was needed to abolish tyrosine phosphorylation of TGBp3. Substitution of Tyr
87–89
with alanine residues enhanced the interaction between TGBp3 and TGBp2 and inhibited cell-to-cell movement of PMTV. On the other hand, substitution of Tyr
120
with alanine resulted in no alteration in the interaction of TGBp3 with TGBp2, but the mutant virus was not infectious. The results suggest that tyrosine phosphorylation is a mechanism regulating the functions of plant virus movement proteins.
Oxysterol-Binding Protein Family I Is the Target of Minor Enviroxime-Like Compounds
Authors: Arita Minetaro , Kojima Hirotatsu , Nagano Tetsuo , Okabe Takayoshi , Wakita Takaji , Shimizu Hiroyuki
Published: January 2013

Enviroxime is an antipicornavirus compound that targets host phosphatidylinositol 4-kinase III beta (PI4KB) activity for its antipicornavirus activity. To date, several antipoliovirus (PV) compounds similar to enviroxime that are associated with a common resistance mutation in viral protein 3A (a G5318A [3A-Ala70Thr] mutation in PV) have been identified. Most of these compounds have a direct inhibitory effect on PI4KB activity, as well as enviroxime (designated major enviroxime-like compounds). However, one of the compounds, AN-12-H5, showed no inhibitory effect on PI4KB and was considered to belong to another group of enviroxime-like compounds (designated minor enviroxime-like compounds). In the present study, we performed a small interfering RNA (siRNA) sensitization assay targeting PI4KB-related genes and identified oxysterol-binding protein (OSBP) as a target of minor enviroxime-like compounds. Knockdown of OSBP and OSBP2 increased the anti-PV activities of AN-12-H5 and a newly identified minor enviroxime-like compound, T-00127-HEV2, and also to T-00127-HEV1 to a minor extent, in the cells. A ligand of OSBP, 25-hydroxycholesterol (25-HC), acted as a minor enviroxime-like compound. Minor enviroxime-like compounds induced relocalization of OSBP to the Golgi apparatus in cells. Treatment of the cells with major or minor enviroxime-like compounds suppressed the expression of genes (HMGCS1 and SQLE) in the SREBP/SCAP regulatory pathway and diminished endogenous phosphatidylinositol 4-phosphate (PI4P) at the Golgi apparatus. Our results suggested that minor enviroxime-like compounds are phenotypically identical to 25-HC and that major and minor enviroxime-like compounds suppress the production and/or accumulation of PI4P in PV-infected cells by targeting PI4KB and OSBP family I activities, respectively.
Purpura fulminans in a patient with mixed connective tissue disease
Authors: Murad Aizuri A , Jeffers Michael , Tobin Anne-Marie , Connolly Maureen
Published: January 2013

A 43-year-old lady was admitted to the intensive care unit with sepsis. She had a history of mixed connective tissue disease, Raynaud's syndrome and hypothyroidism. 2 days later, she developed a purpuric rash on her face and extremities with a livedoid background. Few days later, her distal fingers and toes became gangrenous which then had to be amputated. Laboratory investigations showed that she was coagulopathic and had multiple organ dysfunctions. Antiphospholipid antibodies were negative; however, protein C and antithrombin III levels were low. A skin biopsy showed fibrinoid necrosis in the vessel wall with microthrombi and red-cell extravasation. A diagnosis of purpura fulminans was made.
Prenatal diagnosis of absent pulmonary valve confirmed by autopsy
Authors: Vivek G , Shetty Ranjan K , Nayak Shalini S , Girisha K M , Naha Kushal
Published: January 2013

Absent pulmonary valve syndrome (APVS) is a rare congenital cardiac anomaly. This syndrome is comprised of subtotal or total absence of pulmonary valve leaflets, stenosis of the pulmonary artery orifice, aneurysmal dilation of the main pulmonary artery and ventricular septal defect. We report a case of APVS with neural tube defect detected prenatally at 22 weeks of gestation by echocardiography, and subsequently confirmed by autopsy of the still born fetus. The common presentations, means of diagnosis and variants of APVS are discussed in brief.
Invasive non-typhoidal salmonella infection with multifocal seeding in an immunocompetent host: an emerging disease in the developed world
Authors: Hall Rebecca Louise , Partridge Rebecca , Venkatraman Navin , Wiselka Martin
Published: January 2013

We report an immunocompetent 24-year-old man who presented with a severe, invasive non-typhoidal salmonella (iNTS) infection. He presented with lumbar back pain associated with fever and rigours, which had been preceded by diarrhoea. Blood cultures grewSalmonella enteritidis. An MRI scan of his pelvis and spine showed that he had a small gluteal abscess and sacroiliitis. His condition subsequently deteriorated due to the development of a secondary pneumonia and respiratory failure. He was managed conservatively with 2 weeks of intravenous ceftriaxone, followed by 6 weeks of oral ciprofloxacin. Detailed investigations did not reveal any predisposing factors or evidence of an underlying immunodeficiency. Follow-up showed complete resolution of symptoms with no long-term sequelae.
Atypical intraoperative anaphylactic shock with ECG changes secondary to non-ruptured hepatic hydatid cyst
Authors: Alansari Mariam , Alsanouri Ibrahim
Published: January 2013

A 62-year-old woman was admitted to the hospital for removal of hydatid cyst from the liver. Intraoperatively, the patient suddenly became hypotensive with tachycardia and ST segment elevation. There was no erythema, bronchospasm or desaturation. Anaesthetic agents were stopped and oxygen fraction was increased. In view of the recurrence of hypotension, she was admitted to the intensive care unit (ICU) without completion of surgery. She was successfully resuscitated and acute myocardial infarction was ruled out. She was managed for the possibility of anaphylaxis with hydration, dopamine, antihistamin and hydrocortisone. After stabilisation, she was taken back to the theatre and the cyst was then removed. Histopathology confirmed hydatid disease of the liver. The patient was discharged from the ICU and then from the hospital in 6 days. Anaphylaxis secondary to hydatid disease is uncommon; however, the possibility of such a diagnosis in all patients with non-ruptured hydatid disease in the endemic areas that develop intraoperative shock should be considered.
The development of healthy tennis clubs in the Netherlands
Authors: Pluim Babette M , Earland Jane , Pluim Nicole E
Published: January 2013

Objectives

To explore the factors that facilitate or hinder the development of healthy tennis clubs in the Netherlands and to identify suitable interventions that would help clubs to reach ‘healthy club’ status.

Methods

A maximum variation, purposive sampling strategy was used to identify and recruit board members (n=16) from 10 Dutch tennis clubs. Data were collected using in-depth interviews based on an interview guide. The interviews explored what steps the clubs had taken to create a healthy tennis club, and what the respondents perceived to be the barriers to reaching healthy club status. The data were analysed using thematic content analysis. An ecological model was used to frame the interpretation of the themes and guide the development of the interventions.

Results

Four emerging themes were identified: provision of healthy foods, injury prevention and health services, social health and safety around the club. The main facilitators were found to be support from club management, having appropriate policies in place and having appointed officers. The main barriers were identified as a lack of policy templates, inadequate knowledge of coaches on injury prevention and injury management and fragmented access to relevant information.

Conclusions

Guided by an ecological model, this study demonstrates the many factors that influence tennis clubs and the individual members of a healthy tennis club. Using this model, a multilevel intervention framework has been created that could be used by the Royal Netherlands Lawn Tennis Association to increase the number of healthy tennis clubs in the Netherlands.
Vancomycin Ophthalmic Ointment 1% for methicillin-resistantStaphylococcus aureusor methicillin-resistantStaphylococcus epidermidisinfections: a case series
Authors: Sotozono Chie , Fukuda Masahiko , Ohishi Masao , Yano Keiko , Origasa Hideki , Saiki Yoshinori , Shimomura Yoshikazu , Kinoshita Shigeru
Published: January 2013

Objectives

To investigate the efficacy and safety of Vancomycin Ophthalmic Ointment 1% (Toa Pharmaceutical Co., Ltd, Toyama, Japan) in patients with external ocular infections caused by methicillin-resistantStaphylococcus aureus(MRSA) or methicillin-resistantStaphylococcus epidermidis(MRSE).

Design

A case series.

Setting

This study was a multicentre, open-label, uncontrolled study in Japan approved as orphan drug status.

Participants

Patients with MRSA or MRSE external ocular infections unresponsive to the treatment of fluoroquinolone eye drops.

Interventions

Vancomycin Ophthalmic Ointment 1% was administered four times daily.

Primary and secondary outcome measures

The subjective and objective clinical scores and bacterial cultures were collected at days 0 (baseline), 3, 7 and 14. The primary outcome was clinical response evaluation (efficacy rate) determined ascomplete response,partial response,no responseandworsening. Secondary outcome was the eradication of the bacteria. Safety was assessed by adverse events including cases in which neither MRSA nor MRSE was detected.

Results

Twenty-five cases with MRSA (20) or MRSE (5) infections were enrolled. Of these 25 cases, 4 discontinued the treatment due to the negative results for bacterial culture during screening or at baseline. Of the 21 cases with conjunctivitis (14), blepharitis (3), meibomitis (1), dacryocystitis (2) or keratitis (1), 14 (66.7%) cases were evaluated as being excellently (complete response, 2 cases) or well (partial response, 12 cases) treated. The eradication rates were 68.4% in MRSA (13 of 19 cases) and 100% in MRSE (2 of 2 cases). Ten adverse events occurred in 7 (28.0%) of 25 cases at the local administration site.

Conclusions

Vancomycin Ophthalmic Ointment 1% was considered to be useful for the treatment of intractable ocular MRSA/MRSE infections.
Ensuring equine biosecurity at London 2012
Authors: Slater Josh
Published: February 2013

The London 2012 Olympic and Paralympic Equestrian Games were the highest profile event in the 2012 equestrian calendar and were the culmination of four years of detailed and meticulous biosecurity planning to ensure that all horses arrived, competed and returned home safely and in good health. Josh Slater, Anthony Greenleaves and Andy Paterson describe how this was achieved