bluuebunny/crossref_metadata_2025 huggingface dataset:
Attempted salvage of infected cardiovascular implantable electronic devices: Are there clinical factors that predict success?
Authors: Peacock James E. , Stafford Jeanette M. , Le Katherine , Sohail Muhammad Rizwan , Baddour Larry M. , Prutkin Jordan M. , Danik Stephan B. , Vikram Holenarasipur R. , Hernandez‐Meneses Marta , Miró José M. , Blank Elisabeth , Naber Christoph K. , Carrillo Roger G. , Greenspon Arnold J. , Tseng Chi‐Hong , Uslan Daniel Z.
Published: March 2018

Background

Published guidelines mandate complete device removal in cases of cardiovascular implantable electronic device (CIED) infection. Clinical predictors of successful salvage of infected CIEDs have not been defined.

Methods

Data from the Multicenter Electrophysiologic Device Infection Collaboration, a prospective, observational, multinational cohort study of CIED infection, were used to investigate whether clinical predictors of successful salvage of infected devices could be identified.

Results

Of 433 adult patients with CIED infections, 306 (71%) underwent immediate device explantation. Medical management with device retention and antimicrobial therapy was initially attempted in 127 patients (29%). “Early failure” of attempted salvage occurred in 74 patients (58%) who subsequently underwent device explantation during the index hospitalization. The remaining 53 patients (42%) in the attempted salvage group retained their CIED. Twenty‐six (49%) had resolution of CIED infection (successful salvage group) whereas 27 patients (51%) experienced “late” salvage failure. Upon comparing the salvage failure group, early and late (N = 101), to the group experiencing successful salvage of an infected CIED (N = 26), no clinical or laboratory predictors of successful salvage were identified. However, by univariate analysis, coagulase‐negative staphylococci as infecting pathogens (P = 0.0439) and the presence of a lead vegetation (P = 0.024) were associated with overall failed salvage.

Conclusions

In patients with definite CIED infections, clinical and laboratory variables cannot predict successful device salvage. Until new data are forthcoming, device explantation should remain a mandatory and early management intervention in patients with CIED infection in keeping with existing expert guidelines unless medical contraindications exist or patients refuse device removal.
External implantable defibrillator as a bridge to reimplant after explant for infection: Experience from two centers
Authors: Dell'Era Gabriele , Ziacchi Matteo , Prenna Eleonora , Diemberger Igor , Varalda Marco , Martignani Cristian , Guerra Federico , Biffi Mauro , Occhetta Eraldo
Published: March 2018

Background

The management of patients explanted for implantable converter defibrillator (ICD) infections may be complex when anti‐bradycardia pacing and tachyarrhythmia protection are needed. We aimed to test the efficacy and safety of a conventional ICD externally connected to a transvenous dual‐coil lead as bridging therapy before the reimplantation.

Methods and results

We enrolled seven patients explanted for ICD infections and needed prolonged antibiotic therapy in two high‐volume hospitals in Italy and treated them with a passive‐can external ICD for a mean of 13 (4–30) days before reimplant. One patient experienced an electrical storm, efficaciously recognized by the external ICD and treated with antitachycardia pacing and shocks. On‐demand pacing was granted for all the patients. No device‐related complications were reported.

Conclusions

An external ICD seems safe and efficacious as a bridge to reimplant in patients explanted for ICD infections.
Epidural Abscess During a Spinal Cord Stimulator Trial: A Case Report
Authors: Wetherington Brian , Khan Talal W.
Published: March 2018

Background

Spinal cord stimulation (SCS) can be beneficial for low back and radicular pain. A short trial of SCS evaluates the potential effectiveness of this therapy for a specific patient, while also decreasing the likelihood of a failed permanent implant. While rare, an epidural abscess is difficult to diagnose based on its nonspecific and unreliable clinical presentation.

Case

We present a case of an acute‐onset methicillin‐sensitive Staphylococcus aureus epidural abscess 72 to 96 hours into a trial of a percutaneous spinal cord stimulator. The patient had no prior medical history of an immunocompromised state or other significant risk factors.

Discussion

An epidural abscess can rapidly arise from an SCS trial despite strict aseptic technique and prophylactic pre‐procedural antibiotics. Spinal epidural abscesses are being detected earlier, and an increasing number of patients are being managed medically. However, it may be challenging to differentiate focal back pain from acute or chronic pain, expected post‐procedural pain, and a new entity such as an abscess.
Giving dyadic data analysis away: A user‐friendly app for actor–partner interdependence models
Authors: STAS LARA , KENNY DAVID A. , MAYER AXEL , LOEYS TOM
Published: March 2018

The actor–partner interdependence model (APIM) is widely used for analyzing dyadic data. Although dyadic research has become immensely popular, its statistical complexity can be a barrier. To remedy this, a free user‐friendly web application, called APIM_SEM, has been developed. This app automatically performs the statistical analyses (i.e., structural equation modeling) of both simple and complex APIMs. It allows the researcher to analyze distinguishable or indistinguishable dyads, to examine dyadic patterns, to estimate actor and partner effects of one or two predictors, and to control for covariates. Results are provided in software and text format, complemented by summary tables and figures. As an illustration, the effect of perception of the partner on satisfaction is assessed by fitting APIMs with varying complexity.
Granulomatous responses in larval taeniid infections
Authors: Díaz Á. , Sagasti C. , Casaravilla C.
Published: March 2018

Granulomas are responses to persistent nonliving bodies or pathogens, centrally featuring specialized macrophage forms called epithelioid and multinucleated giant cells. The larval stages of the cestode parasites of theTaeniidaefamily (Taenia,Echinococcus) develop for years in fixed tissue sites in mammals. In consequence, they are targets of granulomatous responses. The information on tissue responses to larval taeniids is fragmented among host and parasite species and scattered over many decades. We attempt to draw an integrated picture of these responses in solid tissues. The intensity of inflammation around live parasites spans a spectrum from minimal to high, parasite vitality correlating with low inflammation. The low end of the inflammatory spectrum features collagen capsules proximal to the parasites and moderate distal infiltration. The middle of the spectrum is dominated by classical granulomatous responses, whereas the high end features massive eosinophil invasions. Across the range of parasite species, much observational evidence suggests that eosinophils are highly effective at killing larval taeniids in solid tissues, before and during chronic granulomatous responses. The evidence available also suggests that these parasites are adapted to inhibit host granulomatous responses, in part through the exacerbation of host regulatory mechanisms including regulatory T cells andTGF‐β.
Producing Compliant Polluters: Seed Companies and Nitrogen Fertilizer Application in U.S. Corn Agriculture
Authors: Stuart Diana , Houser Matthew
Published: March 2018

The majority of research to date has attributed the pollution problems associated with agriculture to the independent decisions of individual farmers; in this article, we illustrate how seed companies' subtle forms of coercion encourage farmers to become compliant polluters. We focus on corn farmers in the midwestern United States, whose management decisions have become increasingly controlled by seed companies. Beyond obvious forms of control, seed companies influence farmers in ways that are less apparent. Drawing from Foucault's concept of disciplinary power, we explore how seed companies have encouraged farmers to increase their application of nitrogen fertilizer through disciplinary mechanisms that naturalize the imposition of constraints. We argue that seed companies employ disciplinary techniques related to the biology of the seed, the product life cycle, and knowledge. While most farmers believe their fertilizer decisions are made independently, these disciplinary techniques compel farmers to increase nitrogen fertilizer application, resulting in increased water pollution and greenhouse gas emissions.
Examining the visual processing patterns of lonely adults
Authors: Bangee Munirah , Qualter Pamela
Published: March 2018

Prior research has shown that loneliness is associated with hypervigilance to social threats, with eye‐tracking research showing lonely people display a specific attentional bias when viewing social rejection and social exclusion video footage (Bangee, Harris, Bridges, Rotenberg & Qualter, 2014; Qualter, Rotenberg, Barrett et al., 2013). The current study uses eye‐tracker methodology to examine whether that attentional bias extends to negative emotional faces and negative social non‐rejecting stimuli, or whether it could be explained only as a specific bias to social rejection/exclusion. It is important to establish whether loneliness relates to a specific or general attention bias because it may explain the maintenance of loneliness. Participants (N = 43, F = 35, Mage = 20 years and 2 months, SD = 3 months) took part in three tasks, where they viewed different social information: Task 1 – slides displaying four faces each with different emotions (anger, afraid, happy and neutral), Task 2 – slides displaying sixteen faces with varying ratios expressing happiness and anger, and Task 3 – slides displaying four visual scenes (socially rejecting, physically threatening, socially positive, neutral). For all three tasks, eye movements were recorded in real time with an eye‐tracker. Results showed no association between loneliness and viewing patterns of facial expressions, but an association between loneliness and hypervigilant viewing of social rejecting stimuli. The findings indicate that lonely adults do not have a generalised hypervigilance to social threat, but have, instead, a specific attentional bias to rejection information in social contexts. Implications of the findings for interventions are discussed.
Credibility estimators with dependence structure over risks and time under balanced loss function
Authors: Zhang Qiang , Chen Ping
Published: March 2018

In this paper, we study the Bühlmann credibility model with constant interest rate and equal dependence structure over risks and time under balanced loss function. By means of orthogonal projection, the inhomogeneous and homogeneous credibility premium estimators are derived, which extend those for the existing models to slightly more general versions. Finally, we investigate the estimation of the structure parameters and present a numerical example to show the effectiveness of the inhomogeneous estimator.
Single‐center outbreak of Pneumocystis jirovecii pneumonia in heart transplant recipients
Authors: Veronese Giacomo , Ammirati Enrico , Moioli Maria Cristina , Baldan Rossella , Orcese Carlo Andrea , De Rezende Gisele , Veronese Silvio , Masciocco Gabriella , Perna Enrico , Travi Giovanna , Puoti Massimo , Cipriani Manlio , Tiberi Simon , Cirillo Daniela , Frigerio Maria
Published: March 2018

Background

Pneumocystis jirovecii pneumonia (PJP) outbreaks are described in solid organ transplant recipients. Few reports suggest interhuman transmission with important infection control implications. We described a large PJP outbreak in heart transplant (HTx) recipients.

Methods

Six cases of PJP occurred in HTx recipients within 10 months in our hospital. Demographics, clinical characteristics, treatment and outcomes were described. To identify contacts among individuals a review of all dates of out‐patient visits and patient hospitalizations was performed. Cross exposure was also investigated using genotyping on PJ isolates.

Results

At the time of PJP‐related hospitalization, patients' mean age was 49 ± standard deviation 4 years, median time from HTx was 8 (25%‐75% interquartile range [Q1‐Q3] 5‐12) months and none of the cases were on prophylaxis. At PJP‐related admission, 5 patients had CMV reactivation, of whom 4 were on antiviral preemptive treatment. Median in‐hospital stay was 30 (Q1‐Q3, 28‐48) days; and 2 cases required intensive care unit admission. All patients survived beyond 2 years. Transmission map analysis suggested interhuman transmission in all cases (presumed incubation period, median 90 [Q1‐Q3, 64‐91] days). Genotyping was performed in 4 cases, demonstrating the same PJ strain in 3 cases.

Conclusions

We described a large PJP cluster among HTx recipients, supporting the nosocomial acquisition of PJP through interhuman transmission. Based on this experience, extended prophylaxis for more than 6 months after HTx could be considered in specific settings. Further work is required to understand its optimal duration and timing based on individual risk factor profiles and to define standardized countermeasures to prevent and limit PJP outbreaks.
Platelet transfusion is not associated with increased mortality or morbidity in patients undergoing cardiac surgery
Authors: Ninkovic Slavisa , McQuilten Zoe , Gotmaker Robert , Newcomb Andrew E. , Cole‐Sinclair Merrole F.
Published: March 2018

BACKGROUND

Transfusion of platelets is common in cardiac surgery, and while there are guidelines for their use, there are concerns about potential risks. We aimed to assess the impact of platelet transfusion on mortality, thrombosis, and infection in this patient group.

STUDY DESIGN AND METHODS

A retrospective cohort study of all patients at St Vincent's Hospital Melbourne who underwent a first cardiac surgery procedure from June 2001 to June 2014 was conducted. A propensity‐weighted analysis was performed to examine the association between intraoperative platelet transfusion and outcomes.

RESULTS

A total of 5233 patients met inclusion criteria, and 531 (10.15%) received intraoperative platelet transfusion (median two platelet doses, interquartile range, 1‐17). Patients receiving platelets were older, had higher body mass index, lower rates of diabetes and dyslipidemia, higher rates of infective endocarditis, recent myocardial infarction and unstable angina, and exposure to aspirin or clopidogrel. On univariable analysis, platelet transfusion was associated with increased 30‐day mortality (2.4% vs. 10.55%, p < 0.001), return to theatre for bleeding (3.23% vs. 13.37%, p < 0.001), and rates of any infection (9.26% vs. 19.17%, p < 0.001). After adjusting for confounders, platelet transfusion was not associated with increased risk of 30‐day mortality or infective complications. Platelet transfusion was associated with higher rates of return to theatre (relative risk [RR], 2.46; confidence interval [CI], 1.42, 4.04; p = 0.001) and decreased risk of thromboembolic events (RR, 0.28; CI, 0.15, 0.51; p < 0.001).

CONCLUSION

Platelet transfusion was not associated with increased mortality or infective complications following first cardiac surgery. Further prospective studies are required to identify patients most likely to benefit from platelet transfusion.
Bilateral retinoschisis in a dog: A veterinary clinical application for optical coherence tomography
Authors: Schaefer Elizabeth A. F. , Whiting Rebecca E. H. , Pearce Jacqueline W. , Grahn Bruce H. , Hamm Charles W. , Moore Cecil P. , Narfström Kristina L.
Published: March 2018

A 11‐year‐old neutered male Labrador retriever‐cross dog was presented to the University of Missouri‐Columbia Veterinary Ophthalmology Service for subtle visual deficits. Indirect ophthalmoscopy revealed a smooth, bullous elevation in the superior‐temporal retina OU. Optical coherence tomography (OCT) performed OU showed inner retinal separation consistent with retinoschisis. Electroretinography (ERG) revealed markedly reduced b‐wave amplitudes in the more severely affected eye (OD) compared with the less severely affected eye (OS). The most notable reductions were in the rod response and 30‐Hz flicker b‐waves OD which were approximately 50% of the corresponding amplitudes OS. Implicit times, particularly the a‐wave implicit times, were noticeably longer OD compared with OS. Lesions remained unchanged over 4 months at which time the dog was humanely euthanized for reasons unrelated to the ocular disease. Significant light microscopic ocular findings were bilateral superior temporal peripheral retinoschisis. The separation of the retinal tissue was similar between eyes and effectively divided the outer plexiform layer. In addition, thinning of the surrounding retinal layers was present. To the authors’ knowledge, this is the first case of canine retinoschisis diagnosed with OCT, evaluated with electroretinography, and confirmed with light microscopic examination. History, clinical, and diagnostic findings, with the absence of disease progression over time, are analogous with cases of acquired senile retinoschisis in humans.
Relationship between corneal sensitivity, corneal thickness, corneal diameter, and intraocular pressure in normal cats and cats with congenital glaucoma
Authors: Telle Mary R. , Chen Nickolas , Shinsako Daniel , Kiland Julie A. , Oikawa Kazuya , Møller Trane Ralph , McLellan Gillian J.
Published: March 2018

Objective

To determine the effect of feline congenital glaucoma (FCG) on corneal sensitivity, and relationships between corneal sensitivity, central corneal thickness (CT), and corneal diameter (CD).

Animals and Procedures

Corneal sensitivity (estimated by corneal touch threshold [CTT] using Cochet‐Bonnet esthesiometry); CT using ultrasonic pachymetry; intraocular pressure (IOP) using rebound tonometry; and maximal horizontal CD were measured in 16 normal and 14 FCG cats, both males and females, aged 7 months‐3.5 years. All procedures complied with an Institutional Animal Care and Use Committee‐approved protocol. Data were analyzed by linear regression: paired Student's t tests for between‐eye comparisons, and unpaired Student's t tests for comparisons between groups. Relationships between parameters were evaluated by Pearson correlation coefficients and linear mixed effects modeling. For statistical tests, with the exception of values that were Benjamini‐Hochberg adjusted for multiple comparisons, P‐values < 0.05 were considered significant.

Results

Mean CTT and CT values were lower in FCG eyes relative to normal eyes, but differences were not statistically significant. Mean CD was significantly larger in FCG eyes relative to normal eyes, and there was a significant negative correlation between CD and CTT in FCG (r = −0.8564, corrected P = 0.005). These associations were confirmed in linear mixed effects models.

Conclusions

Eyes with FCG have significantly larger CDs when compared with normal eyes, and larger CDs correlated with decreased corneal sensitivity in this group. Further studies are warranted to explore the effect of buphthalmos and corneal enlargement on corneal sensitivity and innervation in feline subjects with chronic glaucoma.
Implementation of an Evidence‐Based Practice Nursing Handover Tool in Intensive Care Using the Knowledge‐to‐Action Framework
Authors: Spooner Amy J. , Aitken Leanne M. , Chaboyer Wendy
Published: March 2018

Background

Miscommunication during handover has been linked to adverse patient events and is an international patient safety priority. Despite the development of handover resources, standardized handover tools for nursing team leaders (TLs) in intensive care are limited.

Aims

The study aim was to implement and evaluate an evidence‐based electronic minimum data set for nursing TL shift‐to‐shift handover in the intensive care unit using the knowledge‐to‐action (KTA) framework.

Methods

This study was conducted in a 21‐bed medical‐surgical intensive care unit in Queensland, Australia. Senior registered nurses involved in TL handover were recruited. Three phases of the KTA framework (select, tailor, and implement interventions; monitor knowledge use; and evaluate outcomes) guided the implementation and evaluation process. A postimplementation practice audit and survey were carried out to determine nursing TL use and perceptions of the electronic minimum data set 3 months after implementation. Results are presented using descriptive statistics (median, IQR, frequency, and percentage).

Results

Overall (86%, n = 49), TLs’ use of the electronic minimum data set for handover and communication regarding patient plan increased. Key content items, however, were absent from handovers and additional documentation was required alongside the minimum data set to conduct handover. Of the TLs surveyed (n = 35), those receiving handover perceived the electronic minimum data set more positively than TLs giving handover (n = 35). Benefits to using the electronic minimum data set included the patient content (48%), suitability for short‐stay patients (16%), decreased time updating (12%), and printing the tool (12%). Almost half of the participants, however, found the minimum data set contained irrelevant information, reported difficulties navigating and locating relevant information, and pertinent information was missing. Suggestions for improvement focused on modifications to the electronic handover interface.

Linking Evidence to Action

Prior to developing and implementing electronic handover tools, adequate infrastructure is required to support knowledge translation and ensure clinician and organizational needs are met.
The effect of community-based health insurance schemes on utilization of healthcare services in low- and middle-income countries: a systematic review protocol of quantitative evidence
Authors: Likka Melaku Haile , Handalo Dejene Melese , Weldsilase Yetnayet Abebe , Sinkie Shimeles Ololo
Published: March 2018

Review question/objective:

The objective of this systematic review is to identify, appraise and synthesize evidence to establish the effectiveness of community-based health insurance (CBHI) schemes in enhancing the utilization of healthcare services among their members in low- and middle-income countries (LMICs).

Specifically, the review objective is to determine if individuals or households enrolled in CBHI schemes in LMICs utilize healthcare services (outpatient visits, hospital admissions, emergency visits, maternal and child healthcare services, or any other services involving the schemes) more frequently than those not included in CBHI schemes.
The patient/significant other experience of physical restraint in acute care settings: a qualitative systematic review protocol
Authors: Lockwood Craig , Stannard Daphne , Munn Zachary , Porritt Kylie , Carrier Judith , Rittenmeyer Leslie , Bjerrum Merete , Salmond Susan
Published: March 2018

Review question:

The overarching question for this qualitative systematic review is: What meanings are attributed to the experience of physical restraint among adult patients or their significant others in acute care hospitals? Specifically the review will seek to answer two questions:

How do adults who have or are being restrained experience this intervention?

How do family/significant others who visit an adult inpatient who is or has been restrained experience the intervention?
Fever dilemma
Authors: Vogel Gretchen
Published: March 2018

When malaria isn't the cause, clinics in the developing world often have little to offer.
Observation of topological superconductivity on the surface of an iron-based superconductor
Authors: Zhang Peng , Yaji Koichiro , Hashimoto Takahiro , Ota Yuichi , Kondo Takeshi , Okazaki Kozo , Wang Zhijun , Wen Jinsheng , Gu G. D. , Ding Hong , Shin Shik
Published: March 2018

A topological superconductor

A promising path toward topological quantum computing involves exotic quasiparticles called the Majorana bound states (MBSs). MBSs have been observed in heterostructures that require careful nanofabrication, but the complexity of such systems makes further progress tricky. Zhang
et al.
identified a topological superconductor in which MBSs may be observed in a simpler way by looking into the cores of vortices induced by an external magnetic field. Using angle-resolved photoemission, the researchers found that the surface of the iron superconductor FeTe
0.55
Se
0.45
satisfies the required conditions for topological superconductivity.

Science
, this issue p.
182
A liquid-liquid transition in supercooled aqueous solution related to the HDA-LDA transition
Authors: Woutersen Sander , Ensing Bernd , Hilbers Michiel , Zhao Zuofeng , Angell C. Austen
Published: March 2018

Unmasking supercooled water transitions

The unusual thermodynamic properties of water suggest that when supercooled, a second critical point should exist between two liquid phases that differ in density. Pure water crystallizes before such conditions can be reached. Woutersen
et al.
studied hydrazinium trifluoroacetate solutions that have similar hydrogen bonding to that of water. They observed a liquid-liquid transition near 190 K by using infrared spectroscopy and calorimetry. The liquid states were analogous to the predicted high- and low-density amorphous phases of water.

Science
, this issue p.
1127
Harmful networks in the brain and beyond
Authors: Winkler Frank , Wick Wolfgang
Published: March 2018

Membrane tubes can connect cancer cells and drive tumor progression and resistance
Translocation of a gut pathobiont drives autoimmunity in mice and humans
Authors: Manfredo Vieira S. , Hiltensperger M. , Kumar V. , Zegarra-Ruiz D. , Dehner C. , Khan N. , Costa F. R. C. , Tiniakou E. , Greiling T. , Ruff W. , Barbieri A. , Kriegel C. , Mehta S. S. , Knight J. R. , Jain D. , Goodman A. L. , Kriegel M. A.
Published: March 2018

Bacterial involvement in autoimmunity

The composition of the commensal microbiota is known to influence autoimmune disease development and persistence. Manfredo Vieira
et al.
identified a gut microbe,
Enterococcus gallinarum
, that translocates from the gut into the organs of mice with a genetic predisposition to lupus-like autoimmunity (see the Perspective by Citi). Molecular signatures of gut barrier disintegration and pathogenic T helper cells were evident in the gut, liver, and lymphoid organs during colonization with the pathobiont. The ensuing pathology could be reversed by vancomycin treatment and by vaccination against
E. gallinarum
. The same bug was also found in liver biopsies of autoimmune patients, but not in healthy controls.

Science
, this issue p.
1156
; see also p.
1097
Proteoforms as the next proteomics currency
Authors: Smith Lloyd M. , Kelleher Neil L.
Published: March 2018

Identifying precise molecular forms of proteins can improve our understanding of function
Signaling by a Conserved Quorum Sensing Pathway Contributes to Growth
Ex Vivo
and Oropharyngeal Colonization of Human Pathogen Group A Streptococcus
Authors: Makthal Nishanth , Do Hackwon , VanderWal Arica R. , Olsen Randall J. , Musser James M. , Kumaraswami Muthiah
Published: March 2018

Bacterial virulence factor production is a highly coordinated process. The temporal pattern of bacterial gene expression varies in different host anatomic sites to overcome niche-specific challenges. The human pathogen group A streptococcus (GAS) produces a potent secreted protease, SpeB, that is crucial for pathogenesis. Recently, we discovered that a quorum sensing pathway comprised of a leaderless short peptide, SpeB-inducing peptide (SIP), and a cytosolic global regulator, RopB, controls
speB
expression in concert with bacterial population density. The SIP signaling pathway is active
in vivo
and contributes significantly to GAS invasive infections. In the current study, we investigated the role of the SIP signaling pathway in GAS-host interactions during oropharyngeal colonization. The SIP signaling pathway is functional during growth
ex vivo
in human saliva. SIP-mediated
speB
expression plays a crucial role in GAS colonization of the mouse oropharynx. GAS employs a distinct pattern of SpeB production during growth
ex vivo
in saliva that includes a transient burst of
speB
expression during early stages of growth coupled with sustained levels of secreted SpeB protein. SpeB production aids GAS survival by degrading LL37, an abundant human antimicrobial peptide. We found that SIP signaling occurs during growth in human blood
ex viv
o. Moreover, the SIP signaling pathway is critical for GAS survival in blood. SIP-dependent
speB
regulation is functional in strains of diverse
emm
types, indicating that SIP signaling is a conserved virulence regulatory mechanism. Our discoveries have implications for future translational studies.
Determinants of Raft Partitioning of the Helicobacter pylori Pore-Forming Toxin VacA
Authors: Raghunathan Krishnan , Foegeding Nora J. , Campbell Anne M. , Cover Timothy L. , Ohi Melanie D. , Kenworthy Anne K.
Published: March 2018

Helicobacter pylori
, a Gram-negative bacterium, is a well-known risk factor for gastric cancer.
H. pylori
vacuolating cytotoxin A (VacA) is a secreted pore-forming toxin that induces a wide range of cellular responses. Like many other bacterial toxins, VacA has been hypothesized to utilize lipid rafts to gain entry into host cells. Here, we used giant plasma membrane vesicles (GPMVs) as a model system to understand the preferential partitioning of VacA into lipid rafts. We show that a wild-type (WT) toxin predominantly associates with the raft phase. Acid activation of VacA enhances binding of the toxin to GPMVs but is not required for raft partitioning. VacA mutant proteins with alterations at the amino terminus (resulting in impaired membrane channel formation) and a nonoligomerizing VacA mutant protein retain the ability to preferentially associate with lipid rafts. Consistent with these results, the isolated VacA p55 domain was capable of binding to lipid rafts. We conclude that the affinity of VacA for rafts is independent of its capacity to oligomerize or form membrane channels.
Rapid Arbitrary PCR Insertion Libraries, a New Tool for Defining Bacterial Promoter Regions
Authors: Matson Jyl S.
Published: March 2018

In this issue, Hustmyer and colleagues (C. M. Hustmyer, C. A. Simpson, S. G. Olney, M. L. Bochman, and J. C. van Kessel, J Bacteriol 200:e00724-17, 2018) describe a new method for rapidly generating reporter libraries. This technique,
r
apid
a
rbitrary PCR
i
nsertion
l
ibraries (RAIL), uses arbitrary PCR and isothermal DNA assembly to insert random fragments of promoter regions into reporter plasmids, resulting in libraries that can be screened to identify regions required for gene expression. This technique will likely be useful for a number of different genetic applications.
Depletion of the Insulator Protein CTCF Results in Herpes Simplex Virus 1 Reactivation
In Vivo
Authors: Washington Shannan D. , Edenfield Samantha I. , Lieux Caroline , Watson Zachary L. , Taasan Sean M. , Dhummakupt Adit , Bloom David C. , Neumann Donna M.
Published: March 2018

Herpes simplex virus 1 (HSV-1) establishes a lifelong latent infection in host peripheral neurons, including the neurons of the trigeminal ganglia (TG). HSV-1 can reactivate from neurons to cause recurrent infection. During latency, the insulator protein CTCF occupies DNA binding sites on the HSV-1 genome, and these sites have been previously characterized as functional enhancer-blocking insulators. Previously, CTCF was found to be dissociated from wild-type virus postreactivation but not in mutants that do not reactivate, indicating that CTCF eviction may also be an important component of reactivation. To further elucidate the role of CTCF in reactivation of HSV-1, we used recombinant adeno-associated virus (rAAV) vectors to deliver a small interfering RNA targeting CTCF to peripheral neurons latent with HSV-1 in rabbit TG. Our data show that CTCF depletion resulted in long-term and persistent shedding of infectious virus in the cornea and increased ICP0 expression in the ganglia, indicating that CTCF depletion facilitates HSV-1 reactivation.

IMPORTANCE
Increasing evidence has shown that the insulator protein CTCF regulates gene expression of DNA viruses, including the gammaherpesviruses. While CTCF occupation and insulator function control gene expression in DNA viruses, CTCF eviction has been correlated to increased lytic gene expression and the dissolution of transcriptional domains. Our previous data have shown that in the alphaherpesvirus HSV-1, CTCF was found to be dissociated from the HSV-1 genome postreactivation, further indicating a global role for CTCF eviction in the transition from latency to reactivation in HSV-1 genomes. Using an rAAV8, we targeted HSV-1-infected peripheral neurons for CTCF depletion to show that CTCF depletion precedes the shedding of infectious virus and increased lytic gene expression
in vivo
, providing the first evidence that CTCF depletion facilitates HSV-1 reactivation.
Contribution of NK Cell Education to both Direct and Anti-HIV-1 Antibody-Dependent NK Cell Functions
Authors: Kristensen Anne B. , Kent Stephen J. , Parsons Matthew S.
Published: March 2018

Antibody Fc-dependent functions are linked to prevention and control of HIV-1 infection. Basic NK cell biology is likely key to understanding the contributions that anti-HIV-1 antibody-dependent NK cell activation and cytolysis make to HIV-1 susceptibility and disease progression. The importance of NK cell education through inhibitory receptors specific for self-HLA-I in determining the potency of anti-HIV-1 antibody-mediated NK cell activation and cytolysis is controversial. To address this issue more definitively, we utilized HLA-I genotyping, flow cytometry staining panels, and cytolysis assays to assess the functionality of educated and noneducated peripheral blood NK cells. We now demonstrate that educated NK cells are superior in terms of their capacity to become activated and/or mediate cytolysis following anti-HIV-1 antibody-dependent stimulation. The profiles of activation observed were similar to those observed upon direct stimulation of NK cells with target cells devoid of HLA-I. Noneducated NK cells make significantly lower contributions to total NK cell activation than would be expected from their frequency within the total NK cell population (i.e., they are hypofunctional), and educated NK cells make contributions similar to or higher than their frequency in the total NK cell population. Finally, NK cells educated through at least one killer immunoglobulin-like receptor and NKG2A exhibited the most significant difference between actual and expected contributions to the total NK cell response, based on their frequency within the total NK cell population, suggesting that summation of NK cell education through inhibitory receptors determines overall NK cell functionality. These observations have potential implications for understanding HIV-1 vaccine efficacy and disease progression.

IMPORTANCE
NK cells are major mediators of anti-HIV-1 antibody-dependent functions, including cytokine production and cytolysis. The mechanisms controlling the capacity of individual NK cells to mediate antibody-dependent functions remain poorly defined. We now show that NK cell education determines the capacity of NK cells to exhibit anti-HIV-1 antibody-dependent activation and mediate antibody-dependent cellular cytotoxicity. These observations suggest that the process of NK cell education could be of importance for understanding HIV-1 pathogenesis and designing immune-based prophylactics or therapeutics.
Meibomian gland dysfunction and keratopathy are associated with dry eye disease in aniridia
Authors: Landsend Erlend Christoffer Sommer , Pedersen Hilde Røgeberg , Utheim Øygunn Aass , Xiao Jiaxin , Adil Muhammed Yasin , Tashbayev Behzod , Lagali Neil , Dartt Darlene Ann , Baraas Rigmor C , Utheim Tor Paaske
Published: March 2018

Aims

To investigate the aetiology and characteristics of dry eye disease (DED) in a Nordic cohort of patients with congenital aniridia.

Methods

Thirty-four Norwegian and one Danish subject with congenital aniridia and 21 healthy controls were examined. All subjects underwent an extensive dry eye examination, including evaluation of meibomian glands (MGs) by meibography, measurement of tear production and tear film osmolarity and grading of vital staining of the ocular surface. Moreover, slit-lamp biomicroscopy was undertaken, including grading of aniridia-associated keratopathy (AAK).

Results

Mean tear film osmolarity was significantly higher (314±11 mOsmol/L) in patients with aniridia compared with the healthy control group (303±11 mOsmol/L, p=0.002). Vital staining score was higher in the aniridia group (4.3±3.0) compared with healthy controls (2.4±1.6, p=0.02). The degree of staining correlated positively with the stage of AAK (r=0.44, p=0.008) and negatively with corneal sensitivity (r=−0.45, p=0.012). Number of expressible MGs was lower in aniridia subjects (2.9±1.6) than in controls (4.0±1.3, p=0.007). MG loss, staged from 0 to 3, was higher in the aniridia group than in the control group, both in upper eyelid (0.86±0.89 vs 0.10±0.31, p=0.001) and lower eyelid (0.94±0.73 vs 0.30±0.47, p=0.003). Computerised analyses showed thinning (p=0.004) and lower density (p<0.001) of the MGs compared with the healthy population.

Conclusions

Patients with congenital aniridia demonstrate increased tear film osmolarity, ocular surface staining, loss of MGs and lower MG expressibility. We conclude that meibomian gland dysfunction and keratopathy are related to development of DED in aniridia.
Posterior scleral reinforcement using genipin-cross-linked sclera for macular hole retinal detachment in highly myopic eyes
Authors: Zhu Shuang-Qian , Pan An-Peng , Zheng Lin-Yan , Wu Yue , Xue An-Quan
Published: March 2018

Background/aims

To investigate the surgical outcomes of posterior scleral reinforcement (PSR) using genipin-cross-linked sclera to treat macular hole retinal detachment (MHRD) in highly myopic eyes.

Methods

Nineteen patients with high myopia (19 eyes) with MHRD were treated sequentially with genipin-cross-linked PSR and were followed at least for 1 year after the surgery. The best corrected visual acuity (BCVA), axial length (AL), optical coherence tomography (OCT) outcomes and the complications were evaluated.

Results

Macular hole was closed in 73.7% of the eyes, foveal reattachment rate was 100%. The mean logMAR BCVA improved from 1.27±0.55 preoperatively to 0.88±0.55 postoperatively. The preoperative AL (29.88±1.97 mm) was decreased (27.73±1.84 mm) after the operation (p<0.001).

Conclusions

For at least a 1-year period of follow-up, PSR with genipin-cross-linked sclera should be considered as a preferred surgical approach to treat MHRD in highly myopic eyes, especially when foveal retinoschisis is also documented.
Intimate partner violence against young women: prevalence and associated factors in Europe
Authors: Sanz-Barbero Belén , López Pereira Patricia , Barrio Gregorio , Vives-Cases Carmen
Published: March 2018

Background

The magnitude of intimate partner violence (IPV) in young women is a source of increasing concern. The prevalence of IPV has not been analysed in Europe as a whole. The objective was to assess the prevalence and main characteristics of experiencing physical and/or sexual and psychological-only IPV among young women in the European Union and to identify individual and contextual associated risk factors.

Methods

We analysed a cross-sectional subsample of 5976 ever-partnered women aged 18–29 years from the European Union Agency for Fundamental Rights Violence Against Women Survey, 2012. The main outcomes were current physical and/or sexual IPV and lifetime psychological-only IPV. Risk factors were assessed by the prevalence ratio (PR) from multilevel Poisson regression models.

Results

Current prevalence of physical and/or sexual IPV was 6.1%, lifetime prevalence of psychological-only IPV was 28.7%. Having suffered physical and/or sexual abuse by an adult before age 15 was the strongest risk factor for IPV (PR: 2.9 for physical and/or sexual IPV, PR: 1.5 for psychological-only IPV). Other individual risk factors were: perceived major difficulties in living within their household income (PR: 2.6), having children (PR: 1.8) and age 18–24 years (PR: 1.5) for physical/sexual IPV and immigration background for psychological-only IPV (PR: 1.4). Living in countries with a higher prevalence of binge drinking or early school dropout was positively associated with IPV.

Conclusions

Findings show that the fight against violence in young women should consider individual characteristics, childhood experiences of abuse and also structural interventions including reduction of alcohol consumption and improvement in the education-related indicators.
Developing a novel international undergraduate surgical masterclass during a financial crisis: our 4-year experience
Authors: Sideris Michail , Hanrahan John , Tsoulfas Georgios , Theodoulou Iakovos , Dhaif Fatema , Papalois Vassilios , Papagrigoriadis Savvas , Velmahos George , Turner Patricia , Papalois Apostolos
Published: March 2018

Background

Essential Skills in the Management of Surgical Cases (ESMSC) is a novel 3-day international undergraduate surgical masterclass. Its current curriculum (Cores integrated for Research—Ci4R) is built on a tetracore, multiclustered architecture combining high-fidelity and low-fidelity simulation-based learning (SBL), with applied and basic science case-based workshops, and non-technical skills modules. We aimed to report our experience in setting up ESMSC during the global financial crisis.

Methods

We report the evolution of our curriculum’s methodology and summarised the research outcomes related to the objective performance improvement of delegates, the educational environment of the course and the use of mixed-fidelity SBL. Feedback from the last three series of the course was prospectively collected and analysed using univariate statistics on IBM SPSS V.23.

Results

311 medical students across the European Union (EU) were selected from a competitive pool of 1280 applicants during seven series of the course between 2014 and 2017. During this period, curriculum 14 s evolved to the final Ci4R version, which integrates a tetracore structure combining 32 stations of in vivo, ex vivo and dry lab SBL with small group teaching workshops. Ci4R was positively perceived across different educational background students (p>0.05 for any comparison).

Conclusions

ESMSC is considered an innovative and effective multidisciplinary teaching model by delegates, where it improves delegates objective performance in basic surgical skills. Our experience demonstrates provision of high-quality and free surgical education during a financial crisis, which evolved through a dynamic feedback mechanism. The prospective recording and subsequent analysis of curriculum evolution provides a blueprint to direct development of effective surgical education courses that can be adapted to local needs.
Prior treatment with the AMPK activator AICAR induces subsequently enhanced glucose uptake in isolated skeletal muscles from 24-month-old rats
Authors: Oki Kentaro , Arias Edward B. , Kanzaki Makoto , Cartee Gregory D.
Published: March 2018

5′ AMP-activated protein kinase (AMPK) activation may be part of the exercise-induced process that enhances insulin sensitivity. Independent of exercise, acute prior treatment of skeletal muscles isolated from young rats with a pharmacological AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), causes subsequently improved insulin-stimulated glucose uptake (GU). However, efficacy of a single prior AICAR exposure on insulin-stimulated GU in muscles from old animals has not been studied. The purpose of this study was to determine whether brief, prior exposure to AICAR (3.5 h before GU assessment) leads to subsequently increased GU in insulin-stimulated skeletal muscles from old rats. Epitrochlearis muscles from 24-month-old male rats were isolated and initially incubated ±AICAR (60 min), followed by incubation without AICAR (3 h), then incubation ±insulin (50 min). Muscles were assessed for GU (via 3-O-methyl-[3H]-glucose accumulation) and site-specific phosphorylation of key proteins involved in enhanced GU, including AMPK, Akt, and Akt substrate of 160 kDa (AS160), via Western blotting. Prior ex vivo AICAR treatment resulted in greater GU by insulin-stimulated muscles from 24-month-old rats. Prior AICAR treatment also resulted in greater phosphorylation of AMPK (T172) and AS160 (S588, T642, and S704). Glucose transporter type 4 (GLUT4) protein abundance was unaffected by prior AICAR and/or insulin treatment. These findings demonstrate that skeletal muscles from older rats are susceptible to enhanced insulin-stimulated GU after brief activation of AMPK by prior AICAR. Consistent with earlier research using muscles from young rodents, increased phosphorylation of AS160 is implicated in this effect, which was not attributable to altered GLUT4 glucose transporter protein abundance.
Isolation of a post-PKS C–C branching jadomycin from S. venezuelae ISP5230 in the presence of 8-aminooctanoic acid
Authors: MacLeod Jeanna M. , Forget Stephanie M. , Martinez-Farina Camilo F. , Jakeman David L.
Published: March 2018

The jadomycin family of natural products was first identified and characterized by Vining and co-workers at Dalhousie University in the 1990s. Herein, we report findings from a recently developed co-amino acid supplementation culture method with S. venezuelae ISP5230 using 8-aminooctanoic acid, where the major natural product was a jadomycin variant omitting an E-ring (1). These results reinforce that the 3a position is susceptible to nucleophilic addition by cellular metabolites in jadomycin biosynthesis when intramolecular cyclization is unfavorable. Further, the cytotoxicity data for several unsubstituted E-ring jadomycins are reported and discussed.
Increased hydropower potential at Niagara: a scenario-based analysis
Authors: Tahseen Samiha , Drake Jennifer , Karney Bryan W.
Published: March 2018

Research often ranges from incremental innovations of existing approaches to the development of novel methodologies. The current study seeks to combine both paradigms through consideration of a legacy hydro system. Stretched along the border between Canada and the US and regulated by a 1950 treaty, the Niagara River currently provides almost 5000 MW of renewable power. This paper develops a HEC-ResSim representation of the existing reservoir (power) system and uses this model to explore a variety of possible future scenarios. These possibilities will ultimately include considering the sensitivity of the system to climate change, reducing tourist flows, and exploring using additional storage to augment operational flows, although the current paper particularly details the scenario involving increased power diversion by somewhat relaxing treaty restrictions. Such an arrangement is shown to potentially increase monthly hydro discharges by 16% relative to the current baseline, and thus to permit an additional 1050 GWh of annual generation on the Canadian side alone. This preliminary exploratory study simply evaluates the potential hydro benefits by assessing the interplay between various system constraints if treaty provisions were ever to be reconsidered, and thus sets the stage for considering a variety of other scenarios.