bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric emergence delirium: Canadian Pediatric Anesthesiologists' experience
Authors: Rosen H. David , Mervitz Deborah , Cravero Joseph P.
Published: November 2015

Introduction

Pediatric emergence agitation/delirium (ED) is a cluster of behaviors seen in the early postanesthetic period with negative emotional consequences for families and increased utilization of healthcare resources. Many studies have looked at identifying risk factors for ED and at pharmacologic regimens to prevent ED. There are few published reports on treatment options and efficacy for established ED episodes, and essentially no data concerning current practice in the treatment of ED. We sought to elicit the experience and opinions of Canadian Pediatric Anesthesiologists on the incidence of ED in their practice, definitions and diagnostic criteria, preventative strategies, treatments, and their perceived efficacy.

Methods

A web‐based survey was sent to pediatric anesthesiologists working at academic health science centers across Canada. The participants were selected based on being members of the Canadian Pediatric Anesthesia Society (CPAS), which represents the subspecialty in Canada. All members of CPAS who had e‐mail contact information available in the membership database were invited to participate. A total of 209 members out of the total of 211 fulfilled these criteria and were included in the study population.

Results

The response rate was 51% (106/209). Of respondents, 42% felt that ED was a significant problem at their institutions, with 45% giving medication before or during anesthesia to prevent the development of ED. Propofol was the most common medication given to prevent ED (68%) and to treat ED (42%). Total intravenous anesthesia (TIVA) was considered by 38% of respondents as a technique used to prevent ED. Medications used for treatment included propofol (42%), midazolam (31%), fentanyl (10%), morphine (7%), and dexmedetomidine (5%), with 87% of respondents rating effectiveness of treatment as ‘usually works quickly with one dose’.

Discussion

We present information on current practice patterns with respect to prophylaxis and treatment of ED among a specialized group of pediatric anesthesiologists and highlight the importance of further research in improving the treatment of this common and challenging peri‐anesthetic occurrence.
Black Jobs Matter: Racial Inequalities in Conditions of Employment and Subsequent Health Outcomes
Authors: Doede Megan Sarah
Published: November 2015

African‐Americans shoulder an excessive burden of unemployment, precarious employment, and low paying jobs in the United States, which may help explain why they experience some of the worst health outcomes among U.S. citizens. This paper presents a conceptual framework describing this phenomenon. The social determinants of health as described by this framework include racism, social and public policy formation, socioeconomic status, and conditions of employment. The intermediate determinants of health, which include the ability to afford health behavior, depression and addiction, environmental exposures, and access to primary care, are informed by conditions of employment, which leads to poor health outcomes for African‐Americans. This paper will explore in detail these relationships.
Genetic structure and phylogeny of Italian and Czech populations of the cucurbit powdery mildew fungus Golovinomyces orontii inferred by multilocus sequence typing
Authors: Pirondi A. , Kitner M. , Iotti M. , Sedláková B. , Lebeda A. , Collina M.
Published: November 2015

Cucurbit powdery mildew caused by Golovinomyces orontii is a serious disease that affects cucurbit crops in temperate areas. In northern Italy, the species is responsible for the early infections at the beginning of the growing season. However, chasmothecia have never been recorded in Italy and the impact of either asexual or sexual reproduction of G. orontii remains to be determined. To investigate and compare the genetic structure of Italian populations with those from the Czech Republic, where chasmothecia are sporadically recorded, seven housekeeping gene fragments (tef‐1α, csI, ITS, H3, tub2, IGS and mtLSU) were amplified and used in a multilocus sequence typing (MLST) approach. The four‐gamete test was performed to detect recombination between and within populations. Phylogeny was inferred using both Bayesian and minimum evolution analyses. Results from MLST revealed the presence of 141 single nucleotide polymorphisms and the existence of 13 different haplotypes. Phylogenetic analysis revealed the existence of two main distinct phylogenetic groups that were also highly genetically different, confirming that G. orontii is a species complex. Recombination was detected within both the phylogenetic groups and the geographical populations, indicating that sexual reproduction could have occurred. However, considering the lower haplotype diversity and the high frequency of ST3 (17 isolates) and ST7 (eight isolates) haplotypes, the Italian population could be predominantly clonal, while sexual reproduction may occasionally occur due to the introduction of genotypes similar to those from the Czech Republic.
Genome‐wide association and epistasis studies unravel the genetic architecture of sudden death syndrome resistance in soybean
Authors: Zhang Jiaoping , Singh Arti , Mueller Daren S. , Singh Asheesh K.
Published: November 2015

Soybean [Glycine max (L.) Merr.] is an economically important crop that is grown worldwide. Sudden death syndrome (SDS), caused by Fusarium virguliforme, is one of the top yield‐limiting diseases in soybean. However, the genetic basis of SDS resistance, especially with respect to epistatic interactions, is still unclear. To better understand the genetic architecture of soybean SDS resistance, genome‐wide association and epistasis studies were performed using a population of 214 germplasm accessions and 31 914 SNPs from the SoySNP50K Illumina Infinium BeadChip. Twelve loci and 12 SNP–SNP interactions associated with SDS resistance were identified at various time points after inoculation. These additive and epistatic loci together explained 24–52% of the phenotypic variance. Disease‐resistant, pathogenesis‐related and chitin‐ and wound‐responsive genes were identified in the proximity of peak SNPs, including stress‐induced receptor‐like kinase gene 1 (SIK1), which is pinpointed by a trait‐associated SNP and encodes a leucine‐rich repeat‐containing protein. We report that the proportion of phenotypic variance explained by identified loci may be considerably improved by taking epistatic effects into account. This study shows the necessity of considering epistatic effects in soybean SDS resistance breeding using marker‐assisted and genomic selection approaches. Based on our findings, we propose a model for soybean root defense against the SDS pathogen. Our results facilitate identification of the molecular mechanism underlying SDS resistance in soybean, and provide a genetic basis for improvement of soybean SDS resistance through breeding strategies based on additive and epistatic effects.
Causes of endogenous uveitis in cats presented to referral clinics in North Carolina
Authors: Jinks Maggie R. , English Robert V. , Gilger Brian C.
Published: November 2015

Objective

To investigate the causes of endogenous uveitis in cats presenting to referral ophthalmology clinics in North Carolina.

Procedure

Medical records of cats diagnosed with endogenous uveitis at North Carolina State University's College of Veterinary Medicine (NCSU‐CVM) or Animal Eye Care Associates of Cary,NCbetween 2003 and 2015 were reviewed. Inclusion criteria were cats that had complete diagnostic workups, including clinical, clinicopathological, serological, and histopathological data, as well as imaging modalities. Serology was consistently completed for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV), Toxoplasma gondii, and Bartonella spp.

Results

One hundred and twenty cats met the inclusion criteria. Seroprevalence of FeLV(2.7%),FIV(7.3%),FCoV (34.7%),T. gondii(23.7%), and Bartonella spp. (43.2%) was observed, with a combined seroprevalence of 59.2%. Nineteen cats (15.8%) were diagnosed with feline infectious peritonitis (FIP) based on clinical, hematological, serological, histopathological, and necropsy findings. The average age of all cases was 7.62 years, while the average age of cats diagnosed withFIPwas 1.82 years. Neoplasia was diagnosed in six cats (5.0%). No underlying etiology was found in 49 cats (40.8%).

Conclusions

Both idiopathic and neoplastic causes of uveitis were less prevalent than previously reported in studies, while seropositivity was higher than previously reported for the study area. This may be due to improved diagnostic capabilities or that cats with infectious disease were more likely to be referred. Because of the high prevalence ofFIP, young cats with uveitis should be evaluated for hyperglobulinemia andFCoV serology should be performed as minimal diagnostics.
Atypical chorioretinal coloboma in a Golden Retriever: a retinographic, fluoroangiographic, and optical coherence tomography study
Authors: Gonzalez‐Alonso‐Alegre Elisa M. , Rodriguez‐Alvaro Alfonso , Esteban‐Martín Javier
Published: November 2015

Purpose

To report a case of canine atypical chorioretinal coloboma where ophthalmoscopic, fluoroangiographic and optical coherence tomography characteristics are described.

Animal Studied

A 2‐year‐old Golden Retriever dog in which routine ophthalmoscopic examination allowed diagnosis of a posterior coloboma on the left eye.

Procedures

Retinography, fluorescein angiography, and optical coherence tomography were performed to characterize the lesion of the left fundus.

Results

Ophthalmoscopy revealed a pigmented circumscribed lesion dorsal to the optic nerve of the left fundus, surrounded by small areas of hyper‐reflectivity and retinal vessels with an abnormal pattern. Fluoroangiography revealed a constant hypofluorescence of the defect and a complete altered vascular pattern associated with the coloboma. Optical coherence study demonstrated an important craterlike depression showing an atrophic neurosensory retina, and a lack of retinal pigment epithelium and choroidal tissue.

Conclusions

Fluoroangiographic and optical coherence tomographic studies of an atypical chorioretinal coloboma in a dog are reported for the first time. Both imaging techniques are of great importance to characterize this type of congenital defects.
High-brightness miniature column for high-speed multicolumn wafer inspection
Authors: Spallas James , Meisburger Dan , Werder Kurt , Muray Lawrence
Published: November 2015

Using miniature columns in a multicolumn architecture in a high-speed wafer inspection system capable of detecting small defects at speeds compatible with high volume manufacturing is feasible if the columns can deliver enough current to the sample and if they can be scaled sufficiently to meet the throughput requirement. The authors show that miniature columns currently in production can meet the required beam current and spot size specifications by modifying an aperture. Simulations of the column show that, because of the length of the column, Coulomb interactions do not significantly limit the current that can be delivered to the sample. The authors discuss scaling and present reasons why the technologies used to manufacture the production columns are capable of producing columns with dimensions small enough to be arrayed in a multicolumn configuration for high volume manufacturing inspection.
An analysis of cochlear response harmonics: Contribution of neural excitation
Authors: Chertoff M. E. , Kamerer A. M. , Peppi M. , Lichtenhan J. T.
Published: November 2015

In this report an analysis of cochlear response harmonics is developed to derive a mathematical function to estimate the gross mechanics involved in the in vivo transfer of acoustic sound into neural excitation (fTr). In a simulation it is shown that the harmonic distortion from a nonlinear system can be used to estimate the nonlinearity, supporting the next phase of the experiment: Applying the harmonic analysis to physiologic measurements to derive estimates of the unknown, in vivo fTr. From gerbil ears, estimates of fTr were derived from cochlear response measurements made with an electrode at the round window niche from 85 Hz tone bursts. Estimates of fTr before and after inducing auditory neuropathy—loss of auditory nerve responses with preserved hair cell responses from neurotoxic treatment with ouabain—showed that the neural excitation from low-frequency tones contributes to the magnitude of fTr but not the sigmoidal, saturating, nonlinear morphology.
An analysis of control using the weighted sum of spatial gradients in active structural acoustic control for flat panels
Authors: Cao Yin , Sommerfeldt Scott. D. , Johnson William , Blotter Jonathan D. , Ashlani Pegah
Published: November 2015

Active structural acoustic control uses a control metric that when minimized reduces the radiated sound. Previous research has identified the weighted sum of spatial gradients (WSSG) control metric and has shown that it is effective in attenuating the radiated sound power from a plate. The WSSG control metric is computed using weighted measurements of the structural response from four closely spaced accelerometers. In this work, it is shown that the weights used to compute WSSG directly impact the control performance and further understanding into choosing appropriate weights is presented. Weights optimized for single frequencies are investigated and shown to achieve nearly the same performance as minimizing sound power. A set of parameter-based weights for broadband frequency control is also proposed and analyzed. These parameter-based weights are inversely proportional to the square of the flexural wavenumber and can be computed using the ratio of the flexural rigidity to the mass per unit area. Both numerical and experimental results are presented using parameter-based weights for simply supported and clamped plates. The results show that the WSSG control using parameter-based weights is easy to implement and works more effectively than previous methods.
Converging measures of binaural detection yield estimates of precision of coding of interaural temporal disparities
Authors: Bernstein Leslie R. , Trahiotis Constantine
Published: November 2015

This presentation reports binaural detection data obtained using a special set of three stimulus configurations. The configurations are shown to yield “converging” measures that allow one to describe how precision of coding of interaural temporal disparities (ITDs) changes as a function of both reference ITD and the center frequency of the stimuli.
Effectiveness of Ginger Root (Zingiber officinale) on Running-Induced Muscle Soreness and Function: A Pilot Study
Authors: Wilson Patrick B. , Fitzgerald John S. , Rhodes Gregory S. , Lundstrom Chris J. , Ingraham Stacy J.
Published: November 2015

Context:

Analgesics are commonly used by individuals undertaking endurance training; unfortunately, many commonly-used analgesics cause significant adverse effects. Ginger root (Zingiber officinale) has been used effectively as an analgesic in several contexts, but to date, no research is available to evaluate ginger root’s effects in the context of endurance training.

Objective:

Determine whether ginger root supplementation reduces muscle soreness and prevents impairments in muscle function following a long-distance training run.

Design:

Randomized, double-blind, placebo-controlled trial.

Setting:

University marathon training course.

Participants:

Twenty college students (n = 8 for ginger root group and n = 12 for placebo group).

Intervention:

Supplementation with 2.2 g·day–1 of ginger root or placebo for three days before, the day of, and the day after a 20–22 mile training run.

Main Outcome Measures:

Four days before and 24-hr postrun, participants rated soreness on a 100-mm visual analog scale, while vertical jump (VJ), peak force, and average rate of force development (RFD) were assessed during a squat jump. Quade’s rank analysis of covariance was used to assess between-group differences.

Results:

Median (range) soreness during jogging at 24-hr postrun was lower with ginger root supplementation (37 mm, 15–58) compared with placebo (62 mm, 6–85) (F = 4.6, p = .04). No significant differences for VJ, peak force, and RFD were found between groups.

Conclusions:

Ginger root may modestly reduce muscle soreness stemming from long-distance running, although it may have little to no effect on measures of muscle function during a VJ. Future studies should explore the mechanisms responsible for reductions in running-induced muscle soreness, as well as evaluate the benefit-to-risk profile of ginger root in the context of endurance training.
Thorium seen as nuclear's new frontier
Authors: Bagla Pallava
Published: November 2015

Unsung reactor fuel is more abundant than uranium and, proponents say, safer.
An extremely bright gamma-ray pulsar in the Large Magellanic Cloud
Authors:   The Fermi LAT Collaboration, Ackermann M. , Albert A. , Baldini L. , Ballet J. , Barbiellini G. , Barbieri C. , Bastieri D. , Bellazzini R. , Bissaldi E. , Bonino R. , Bottacini E. , Brandt T. J. , Bregeon J. , Bruel P. , Buehler R. , Caliandro G. A. , Cameron R. A. , Caraveo P. A. , Cecchi C. , Charles E. , Chekhtman A. , Cheung C. C. , Chiang J. , Chiaro G. , Ciprini S. , Cohen-Tanugi J. , Cuoco A. , Cutini S. , D’Ammando F. , Desiante F. de Palma R. , Digel S. W. , Di Venere L. , Drell P. S. , Favuzzi C. , Fegan S. J. , Ferrara E. C. , Franckowiak A. , Funk S. , Fusco P. , Gargano F. , Gasparrini D. , Giglietto N. , Giordano F. , Godfrey G. , Grenier I. A. , Grondin M.-H. , Grove J. E. , Guillemot L. , Guiriec S. , Hagiwara K. , Harding A. K. , Hays E. , Hewitt J. W. , Hill A. B. , Horan D. , Johnson T. J. , Knödlseder J. , Kuss M. , Larsson S. , Latronico L. , Lemoine-Goumard M. , Li J. , Li L. , Longo F. , Loparco F. , Lovellette M. N. , Lubrano P. , Maldera S. , Manfreda A. , Marshall F. , Martin P. , Mayer M. , Mazziotta M. N. , Michelson P. F. , Mirabal N. , Mizuno T. , Monzani M. E. , Morselli A. , Moskalenko I. V. , Murgia S. , Naletto G. , Nuss E. , Ohsugi T. , Orienti M. , Orlando E. , Paneque D. , Pesce-Rollins M. , Piron F. , Pivato G. , Porter T. A. , Rainò S. , Rando R. , Razzano M. , Reimer A. , Reimer O. , Reposeur T. , Romani R. W. , Parkinson P. M. Saz , Schulz A. , Sgrò C. , Siskind E. J. , Smith D. A. , Spada F. , Spandre G. , Spinelli P. , Suson D. J. , Takahashi H. , Thayer J. B. , Thompson D. J. , Tibaldo L. , Torres D. F. , Uchiyama Y. , Vianello G. , Wood K. S. , Wood M. , Zampieri L.
Published: November 2015

LMC pulsar's bright gamma-ray flashes

Pulsars are rapidly rotating neutron stars that are seen as pulsating sources of radio waves. Some, such as the Crab pulsar, also emit pulses of gamma rays. The Fermi LAT collaboration observed pulsed gamma rays from a pulsar outside our galaxy, the Milky Way. The pulsar, known as PSR J0540–6919, is located in the Large Magellanic Cloud (LMC). This is the most powerful gamma-ray pulsar yet known, with luminosity 20 times that of the Crab. The findings should help to explain how pulsars convert the energy stored in their rotation into detectable electromagnetic emission.

Science
, this issue p.
801
The deep ocean under climate change
Authors: Levin Lisa A. , Le Bris Nadine
Published: November 2015

The deep ocean absorbs vast amounts of heat and carbon dioxide, providing a critical buffer to climate change but exposing vulnerable ecosystems to combined stresses of warming, ocean acidification, deoxygenation, and altered food inputs. Resulting changes may threaten biodiversity and compromise key ocean services that maintain a healthy planet and human livelihoods. There exist large gaps in understanding of the physical and ecological feedbacks that will occur. Explicit recognition of deep-ocean climate mitigation and inclusion in adaptation planning by the United Nations Framework Convention on Climate Change (UNFCCC) could help to expand deep-ocean research and observation and to protect the integrity and functions of deep-ocean ecosystems.
A gut-vascular barrier controls the systemic dissemination of bacteria
Authors: Spadoni Ilaria , Zagato Elena , Bertocchi Alice , Paolinelli Roberta , Hot Edina , Di Sabatino Antonio , Caprioli Flavio , Bottiglieri Luca , Oldani Amanda , Viale Giuseppe , Penna Giuseppe , Dejana Elisabetta , Rescigno Maria
Published: November 2015

A gut bacterial containment system

Trillions of bacteria selectively inhabit our guts, but how do our bodies keep them contained? Spadoni
et al.
describe a “gut-vascular barrier” that prevents intestinal microbes from accessing the liver and the bloodstream in mice (see the Perspective by Bouziat and Jabri). Studies with human samples and in mice revealed that the cell biology of the gut-vascular barrier shares similarities with the blood-brain barrier of the central nervous system. Pathogenic bacteria such as
Salmonella typhimurium
could penetrate the gut-vascular barrier in mice, gaining access to the liver and bloodstream, in a manner dependent on the
Salmonella
pathogenicity island 2–type III secretion system.

Science
, this issue p.
830
; see also p.
742
Warm-water coral reefs and climate change
Authors: Spalding Mark D. , Brown Barbara E.
Published: November 2015

Coral reefs are highly dynamic ecosystems that are regularly exposed to natural perturbations. Human activities have increased the range, intensity, and frequency of disturbance to reefs. Threats such as overfishing and pollution are being compounded by climate change, notably warming and ocean acidification. Elevated temperatures are driving increasingly frequent bleaching events that can lead to the loss of both coral cover and reef structural complexity. There remains considerable variability in the distribution of threats and in the ability of reefs to survive or recover from such disturbances. Without significant emissions reductions, however, the future of coral reefs is increasingly bleak.
Two Serious Cases of Infection with Clostridium celatum after 40 Years in Hiding?
Authors: Agergaard Charlotte Nielsen , Hoegh Silje Vermedal , Holt Hanne Marie , Justesen Ulrik Stenz
Published: November 2015

Clostridium celatum
[ce.la'tum. L. adj.
celatum
hidden] has been known since 1974, when it was isolated from human feces. In 40 years, no association with human infection has been reported. In this work, we present two serious cases of infection with the anaerobic Gram-positive rod
Clostridium celatum
.
Occurrence of Fungal DNA Contamination in PCR Reagents: Approaches to Control and Decontamination
Authors: Czurda S. , Smelik S. , Preuner-Stix S. , Nogueira F. , Lion T.
Published: November 2015

Nucleic acid amplification techniques permitting sensitive and rapid screening in patients at risk for invasive fungal infections are an important addition to conventional fungal diagnostic methods. However, contamination with fungal DNA may be a serious threat to the validity of fungal amplification-based assays. Besides rigorous handling procedures to avoid false-positive test results from exogenous sources, we have implemented protocols for comprehensive assessment of fungal contamination in all materials involved in the analytical process. Traces of fungal DNA were found in different commercially available PCR reagents, including lyophilized primers, TaqMan probes, and master mix solutions. These contaminants resulted in a considerable rate of false-positive tests in panfungal real-time PCR analysis. To address this problem, we have established a decontamination protocol based on the activity of a double-strand specific DNase. Using this approach, we have significantly reduced the frequency of false-positive test results attributable to contaminated reagents. On the basis of our findings, we strongly recommend routine monitoring of all reagents used in fungal PCR assays for the presence of relevant contaminants. As long as fungal-grade reagents are not readily available, pretreatment methods facilitating elimination of fungal DNA are critical for reducing the risk of false-positive results in highly sensitive molecular fungal detection assays.
Comparison of
illumigene
Group A Streptococcus Assay with Culture of Throat Swabs from Children with Sore Throats in the New Zealand School-Based Rheumatic Fever Prevention Program
Authors: Upton Arlo , Bissessor Liselle , Farrell Elizabeth , Shulman Stanford T. , Zheng Xiaotian , Lennon Diana
Published: November 2015

Group A streptococcal (GAS) pharyngitis is a particularly important condition in areas of New Zealand where the incidence of acute rheumatic fever remains unacceptably high. Prompt diagnosis and treatment of GAS pharyngitis are cornerstones of the Rheumatic Fever Prevention Programme, but these are hindered by the turnaround time of culture. Tests with excellent performance and rapid turnaround times are needed. For this study, throat swabs (Copan ESwabs) were collected from schoolchildren self-identifying with a sore throat. Samples were tested by routine culture and the
illumigene
GAS assay using loop-mediated isothermal amplification. Discrepant results were resolved by retesting of the same specimen by an alternative molecular assay. Seven hundred fifty-seven throat swab specimens were tested by both methods. The performance characteristics of the
illumigene
assay using culture on blood agar as the “gold standard” and following discrepancy analysis were as follows: sensitivity, 82% and 87%, respectively; specificity, 93% and 98%, respectively; positive predictive value, 61% and 88%, respectively; and negative predictive value, 97% and 97%, respectively. In our unique setting of a school-based throat swabbing program, the
illumigene
assay did not perform quite as well as described in previous reports. Despite this, its improved sensitivity and rapid turnaround time compared with those of culture are appealing.
Misidentification of a Rare Species, Cryptococcus laurentii, by Commonly Used Commercial Biochemical Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Systems: Challenges for Clinical Mycology Laboratories
Authors: Xiao Meng , Fan Xin , Chen Xin-Xin , Wang He , Zhang Li , Xu Zhi-Peng , Kudinha Timothy , Kong Fanrong , Xu Ying-Chun
Published: November 2015

Forty-two putative
Cryptococcus laurentii
isolates identified by the Vitek 2 system were collected in China. The gold standard, internal transcribed spacer (ITS) sequencing, confirmed that only two isolates were genuine
C. laurentii
. Bruker Biotyper matrix-assisted laser desorption ionization–time of flight mass spectrometry was able to identify the
C. laurentii
isolates with an expanded custom database.
Characterization of Recombinant Human Cytomegaloviruses Encoding IE1 Mutants L174P and 1-382 Reveals that Viral Targeting of PML Bodies Perturbs both Intrinsic and Innate Immune Responses
Authors: Scherer Myriam , Otto Victoria , Stump Joachim D. , Klingl Stefan , Müller Regina , Reuter Nina , Muller Yves A. , Sticht Heinrich , Stamminger Thomas
Published: November 2015

PML is the organizer of cellular structures termed nuclear domain 10 (ND10) or PML-nuclear bodies (PML-NBs) that act as key mediators of intrinsic immunity against human cytomegalovirus (HCMV) and other viruses. The antiviral function of ND10 is antagonized by viral regulatory proteins such as the immediate early protein IE1 of HCMV. IE1 interacts with PML through its globular core domain (IE1CORE) and induces ND10 disruption in order to initiate lytic HCMV infection. Here, we investigate the consequences of a point mutation (L174P) in IE1CORE, which was shown to abrogate the interaction with PML, for lytic HCMV infection. We found that a recombinant HCMV encoding IE1-L174P displays a severe growth defect similar to that of an IE1 deletion virus. Bioinformatic modeling based on the crystal structure of IE1COREsuggested that insertion of proline into the highly alpha-helical domain severely affects its structural integrity. Consistently, L174P mutation abrogates the functionality of IE1COREand results in degradation of the IE1 protein during infection. In addition, our data provide evidence that IE1COREas expressed by a recombinant HCMV encoding IE1 1-382 not only is required to antagonize PML-mediated intrinsic immunity but also affects a recently described function of PML in innate immune signaling. We demonstrate a coregulatory role of PML in type I and type II interferon-induced gene expression and provide evidence that upregulation of interferon-induced genes is inhibited by IE1CORE. In conclusion, our data suggest that targeting PML by viral regulatory proteins represents a strategy to antagonize both intrinsic and innate immune mechanisms.

IMPORTANCEPML nuclear bodies (PML-NBs), which represent nuclear multiprotein complexes consisting of PML and additional proteins, represent important cellular structures that mediate intrinsic resistance against many viruses, including human cytomegalovirus (HCMV). During HCMV infection, the major immediate early protein IE1 binds to PML via a central globular domain (IE1CORE), and we have shown previously that this is sufficient to antagonize intrinsic immunity. Here, we demonstrate that modification of PML by IE1COREnot only abrogates intrinsic defense mechanisms but also attenuates the interferon response during infection. Our data show that PML plays a novel coregulatory role in type I as well as type II interferon-induced gene expression, which is antagonized by IE1CORE. Importantly, our finding supports the view that targeting of PML-NBs by viral regulatory proteins has evolved as a strategy to inhibit both intrinsic and innate immune defense mechanisms.
Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1
Authors: Yu Xiaoliang , Li Yun , Chen Qin , Su Chenhe , Zhang Zili , Yang Chengkui , Hu Zhilin , Hou Jue , Zhou Jinying , Gong Ling , Jiang Xuejun , Zheng Chunfu , He Sudan
Published: November 2015

Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells.

IMPORTANCE
This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV.
Epstein-Barr Virus gp350 Can Functionally Replace the Rhesus Lymphocryptovirus Major Membrane Glycoprotein and Does Not Restrict Infection of Rhesus Macaques
Authors: Herrman Marissa , Mühe Janine , Quink Carol , Wang Fred
Published: November 2015

Primary Epstein-Barr virus (EBV) infection is the most common cause of infectious mononucleosis, and persistent infection is associated with multiple cancers. EBV vaccine development has focused on the major membrane glycoprotein, gp350, since it is the major target for antibodies that neutralize infection of B cells. However, EBV has tropism for both B cells and epithelial cells, and it is unknown whether serum neutralizing antibodies against B cell infection will provide sufficient protection against virus infection initiated at the oral mucosa. This could be stringently tested by passive antibody transfer and oral virus challenge in the rhesus macaque model for EBV infection. However, only neutralizing monoclonal antibodies (MAbs) against EBV are available, and EBV is unable to infect rhesus macaques because of a host range restriction with an unknown mechanism. We cloned the prototypic EBV-neutralizing antibody, 72A1, and found that recombinant 72A1 did not neutralize rhesus lymphocryptovirus (rhLCV) infection of macaque B cells. Therefore, we constructed a chimeric rhLCV in which the native major membrane glycoprotein was replaced with EBV gp350. This chimeric rhLCV became sensitive to neutralization by the 72A1 MAb, efficiently immortalized macaque B cells
in vitro
, and successfully established acute and persistent infection after oral inoculation of rhesus macaques. Thus, EBV gp350 can functionally replace rhLCV gp350 and does not restrict rhLCV infection
in vitro
or
in vivo
. The chimeric rhLCV enables direct use of an EBV-specific MAb to investigate the effects of serum neutralizing antibodies against B cell infection on oral viral challenge in rhesus macaques.

IMPORTANCE
This study asked whether the EBV major membrane glycoprotein could functionally replace the rhLCV major membrane glycoprotein. We found that an rhLCV humanized with EBV gp350 is capable of efficiently immortalizing monkey B cells
in vitro
and reproduces acute and persistent infection after oral inoculation of macaques. These results advance our understanding of why EBV cannot infect rhesus macaques by proving that viral attachment through gp350 is not the mechanism for EBV host range restriction. Humanization of rhLCV with EBV gp350 also confers susceptibility to a potent EBV-neutralizing MAb and provides a novel and significant enhancement to the rhesus macaque animal model where both the clinical utility and biological role of neutralizing MAbs against B cell or epithelial cell infection can now be directly tested in the most accurate animal model for EBV infection.
Vertebral artery dissection in evolution found during chiropractic examination
Authors: Futch Dan , Schneider Michael J , Murphy Donald , Grayev Allison
Published: November 2015

A 30-year-old woman presented to an emergency department with sudden onset of transient loss of left peripheral vision. Owing to a history of migraine headaches, she was released with a diagnosis of ocular migraine. Two days later, she sought chiropractic care for the chief symptom of severe neck pain. The chiropractor suspected the possibility of vertebral artery dissection (VAD). No manipulation was performed; instead, MR angiography (MRA) of the neck was obtained, which revealed an acute left VAD with early thrombus formation. The patient was placed on aspirin therapy. Repeat MRA of the neck 3 months later revealed resolution of the thrombus, without progression to stroke. This case illustrates the importance for all healthcare providers who see patients with neck pain and headache to be attentive to the symptomatic presentation of possible VAD in progress.
Self-rated chronic conditions and 2-week prevalence in adults in Zhongshan, China: an epidemiological survey
Authors: Zhu Chunyan , Sun Xiaomin , Geng Qingshan , Fu Rong , Yang Hongling , Jiang Wei
Published: November 2015

Objective

To examine the association between behavioural factors and the risk of chronic conditions and 2-week prevalence.

Design

This was a cross-sectional survey.

Setting

The study was conducted in Zhongshan, China.

Participants

A multistage clustering sampling method was used to select a representative sample of residents from the household registration system between July and September 2011. The overall sample replacement rate was 9.4%, and the final sample included 43 028 individuals.

Outcome measures

Chronic conditions and 2-week prevalence.

Results

4979 (11.6%) of the participants reported having at least one chronic condition, 1067 (2.5%) had two or more concurrent chronic conditions, and 6830 (15.9%) reported having at least one disease in a 2-week recall period. The most common chronic condition was primary hypertension, which was reported by 6.8% of participants. Logistic regression models demonstrated that the main factors for having a chronic condition and 2-week prevalence were older age (≥65 years of age; OR 44.91, 95% CI 33.05 to 61.03; and OR 12.71, 95% CI 10.44 to 15.46, respectively), obesity (OR 3.00, 95% CI 2.63 to 3.42; and OR 2.50, 95% CI 2.22 to 2.82, respectively) and being a former smoker (OR 3.02, 95% CI 2.54 to 3.58; and OR 3.24, 95% CI 2.74 to 3.82, respectively).

Conclusions

This study suggests that older age, obesity and unhealthy behaviours are high-risk factors for poorer health status among the residents of Zhongshan, China. The present findings highlight the importance of recognising and managing harmful behaviours in order to improve health.
Testing a model of facilitated reflection on network feedback: a mixed method study on integration of rural mental healthcare services for older people
Authors: Fuller Jeffrey , Oster Candice , Muir Cochrane Eimear , Dawson Suzanne , Lawn Sharon , Henderson Julie , O'Kane Deb , Gerace Adam , McPhail Ruth , Sparkes Deb , Fuller Michelle , Reed Richard L
Published: November 2015

Objective

To test a management model of facilitated reflection on network feedback as a means to engage services in problem solving the delivery of integrated primary mental healthcare to older people.

Design

Participatory mixed methods case study evaluating the impact of a network management model using organisational network feedback (through social network analysis, key informant interviews and policy review).

Intervention

A model of facilitated network reflection using network theory and methods.

Setting

A rural community in South Australia.

Participants

32 staff from 24 services and 12 senior service managers from mental health, primary care and social care services.

Results

Health and social care organisations identified that they operated in clustered self-managed networks within sectors, with no overarching purposive older people's mental healthcare network. The model of facilitated reflection revealed service goal and role conflicts. These discussions helped local services to identify as a network, and begin the problem-solving communication and referral links. A Governance Group assisted this process. Barriers to integrated servicing through a network included service funding tied to performance of direct care tasks and the lack of a clear lead network administration organisation.

Conclusions

A model of facilitated reflection helped organisations to identify as a network, but revealed sensitivity about organisational roles and goals, which demonstrated that conflict should be expected. Networked servicing needed a neutral network administration organisation with cross-sectoral credibility, a mandate and the resources to monitor the network, to deal with conflict, negotiate commitment among the service managers, and provide opportunities for different sectors to meet and problem solve. This requires consistency and sustained intersectoral policies that include strategies and funding to facilitate and maintain health and social care networks in rural communities.
A multilevel study on the association of observer-assessed working conditions with depressive symptoms among female eldercare workers from 56 work units in 10 care homes in Denmark
Authors: Jakobsen Louise M , Jorgensen Anette F B , Thomsen Birthe L , Greiner Birgit A , Rugulies Reiner
Published: November 2015

Objectives

Eldercare workers in Denmark have a higher prevalence of poor psychological health than other occupational groups. We examined the association between working conditions assessed by trained observers and depressive symptoms assessed by self-report in a study of female Danish eldercare workers.

Methods

Working conditions were observed based on action regulation theory and defined as (1) regulation requirements, a workplace resource providing opportunity for decision-making and skill development and (2) barriers for task completion. We examined the associations of individual and work unit averaged working conditions with depressive symptoms in a sample of 95 individually observed eldercare workers. Further, we examined the association of work unit averaged working conditions with depressive symptoms in a sample of 205 care workers, including both observed and non-observed individuals. We used regression models that allowed for correlations within work units and care homes and adjusted these models for demographics, job characteristics and stressful life events.

Results

Higher levels of regulation requirements were associated with lower depressive symptoms at the individual level (p=0.04), but not at the workplace level. Barriers were not associated with depressive symptoms at the individual level. At the workplace level, a higher number of qualitatively different barriers (p=0.04) and a higher number of barriers for equipment use (p=0.03) were associated with lower levels of depressive symptoms in the age and cohabitation adjusted model, however statistical significance was lost in the fully adjusted model.

Conclusions

Low level of regulation requirements was associated with a high level of depressive symptoms. The study highlights the importance of examining both individual and workplace levels of working conditions.
Current-reported outcome domains in studies of adults with a focus on the treatment of tinnitus: protocol for a systematic review
Authors: Hall Deborah A , Szczepek Agnieszka J , Kennedy Veronica , Haider Haúla
Published: November 2015

Introduction

In Europe alone, over 70 million people experience tinnitus. Despite its considerable socioeconomic relevance, progress in developing successful treatments has been limited. Clinical effectiveness is judged according to change in primary outcome measures, but because tinnitus is a subjective condition, the definition of outcomes is challenging and it remains unclear which distinct aspects of tinnitus (ie, ‘domains’) are most relevant for assessment. The development of a minimum outcome reporting standard would go a long way towards addressing these problems. In 2006, a consensus meeting recommended using 1 of 4 questionnaires for tinnitus severity as an outcome in clinical trials, in part because of availability in different language translations. Our initiative takes an approach motivated by clinimetrics, first by determining what to measure before seeking to determine how to measure it. Agreeing on the domains that contribute to tinnitus severity (ie, ‘what’) is the first step towards achieving a minimum outcome reporting standard for tinnitus that has been reached via a methodologically rigorous and transparent process.

Methods and analysis

Deciding what should be the core set of outcomes requires a great deal of discussion and so lends itself well to international effort. This protocol lays out the first-step methodology in defining a Core Domain Set for clinical trials of tinnitus by establishing existing knowledge and practice with respect to which outcome domains have been measured and which instruments used in recent registered and published clinical trials.

Ethics and dissemination

No ethical issues are foreseen. Findings will be reported at national and international ear, nose and throat (ENT) and audiology conferences and in a peer-reviewed journal, using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines.

Trial registration number

The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525.
Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study
Authors: Misawa S , Sato Y , Katayama K , Hanaoka H , Sawai S , Beppu M , Nomura F , Shibuya K , Sekiguchi Y , Iwai Y , Watanabe K , Amino H , Ohwada C , Takeuchi M , Sakaida E , Nakaseko C , Kuwabara S
Published: November 2015

Objective

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome.

Method

This was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12 months (median follow-up, 87 months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival.

Results

Serum VEGF levels decreased rapidly after treatment, and stabilised by 6 months post treatment. Patients with normalised serum VEGF levels (<1040 pg/mL) at 6 months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6 months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12 months.

Conclusions

Serum VEGF level at 6 months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials.