bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Experience and Procedural Outcomes Associated with the DF4 Implantable Cardioverter Defibrillator System: The SJ4 Postapproval Study
Authors: CANTILLON DANIEL J. , HA KIEU , STYPEREK ROBERT , JUMRUSSIRIKUL PITAYADET , MIRRO MICHAEL , WONG WILSON , WILKOFF BRUCE L.
Published: April 2013

Background

Current implantable cardioverter defibrillators (ICDs) employ two or three low‐ and high‐voltage lead connectors, adding complexity and bulk, sometimes resulting in incorrect connections and adverse events. The SJ4 study evaluates the performance of a novel integrated single‐lead DF4 connection system by characterizing lead measurements, handling characteristics, and outcomes.

Methods

Patients with standard guidelines‐based ICD indications were enrolled and implanted with a St. Jude Medical™ DF4 system (St. Jude Medical, Sylmar, CA, USA; right ventricular high‐voltage DF4 lead models 7120Q, 7121Q, 7122Q, or 7170Q with compatible ICD). Device electrical measurements, handling characteristics, and any adverse events were collected at implant and during each scheduled 6‐month follow‐up.

Results

Among 1,701 patients (65 ± 13 years, 72% male, left ventricular ejection fraction 29 ± 12%) enrolled at 58 centers, there were 1,697 successful implants (99.8% implant success; ICD; n = 999, cardiac resynchronization therapy‐defibrillator n = 698). Implanting physicians reported that implantation of the DF4 lead was normal or easier than normal in 94% of cases with successful implant. These patients have been followed for 1.7 ± 0.5 years with a maximum follow‐up of 2.5 years. The complication rate was 0.017 per patient year of follow‐up (95% confidence interval: 0.013–0.023), which included abnormal defibrillation impedance, elevated pacing thresholds, failure to detect ventricular tachycardia/ventricular fibrillation, lead dislodgement, lead fracture, loss of capture, and lead perforation. There were no set screw‐related complications at implant or during follow‐up.

Conclusion

The DF4 system overall performed very well with few complications at implant and in follow‐up.
The Electrophysiological Characteristics of Accessory Pathways in Pediatric Patients with Intermittent Preexcitation
Authors: MAH DOUGLAS Y. , SHERWIN ELIZABETH D. , ALEXANDER MARK E. , CECCHIN FRANK , ABRAMS DOMINIC J. , WALSH EDWARD P. , TRIEDMAN JOHN K.
Published: April 2013

Background

Accessory pathways (APs) with intermittent preexcitation (IPX) are thought to be of lower risk, but there are reports of IPX patients presenting with rapidly conducted atrial fibrillation.

Methods

Retrospective study performed on patients with preexcitation who underwent an electro‐physiological study (EPS). IPX was defined as loss of the delta wave on electrocardiogram prior to EPS. Patients with IPX were compared with those with persistent preexcitation (PPX) or suppression of the delta wave on exercise test (IPX‐ET). Congenital heart disease and prior ablations were excluded.

Results

Of 328 patients with preexcitation, 41 (12.5%) had IPX. Patients with IPX or PPX were similar in age (12.9 years vs 13.0 years, P = 0.8) and AP location (left‐sided 54% vs 50%, P = 0.7; septal 32% vs 35%, P = 0.4). Testing on isoproterenol was performed in 17 (41%) IPX and 41 (14%) PPX patients. Although IPX patients had a longer median refractory period compared to PPX patients (340 ms vs 310 ms, P = 0.001), the incidence of APs with refractory periods ≤250 ms was similar (10% vs 12%, P = 1.0). Exercise tests were performed on 208 patients and 24 (12%) had IPX‐ET. Compared with IPX patients, IPX‐ET had similar median AP refractory periods (320 ms, P = 0.4) and incidence of APs with refractory periods ≤250 ms (13%, P = 1.0).

Conclusion

Patients with IPX had longer AP refractory periods than those with PPX, but the incidence of pathways with refractory periods ≤250 ms was not significantly different. The finding of IPX on a baseline electrocardiogram does not rule out potentially high‐risk pathways.
Feasibility and Safety of Same‐Day Discharge after Implantable Cardioverter Defibrillator Placement for Primary Prevention
Authors: DARDA SABA , KHOURI YAZAN , GORGES RONY , AL SAMARA MERSHED , JAIN SACHIN K. Amruthlal , DACCARETT MARCOS , MACHADO CHRISTIAN
Published: April 2013

Background

In the current age of ever‐increasing healthcare costs, it is of utmost importance to adopt strategies that reduce hospital stay and cost, while still maintaining patient safety. In this study we review our approach of same‐day discharge following implantable cardioverter defibrillator (ICD) placement for primary prevention of sudden cardiac death (SCD).

Methods

We conducted a retrospective chart review of 415 consecutive patients who underwent ICD implantation for prevention of SCD between 2007 and 2010. Patients were divided into an outpatient group (Group A) and an inpatient group (Group B). We evaluated the patients’ demographics, comorbidities, and the rate of short‐term surgical complications on or before the 2‐week follow‐up appointment.

Results

Of 252 patients included in Group A, 198 (78.6%) were successfully discharged on the same day (Group A1). At the 2‐week wound check appointment, four patients (2%) had minor surgical site bleeding, one patient had a hematoma, and one patient developed fever and swelling around the implantation site. Of the Group A patients, 54 (21.4%) were not discharged on the same day (Group A2). A total of 53 patients were included in Group B, four (7.5%) developed a hematoma at the 2‐week follow‐up wound check visit.

Conclusions

Procedure‐related complications after ICD placement are rare. Same‐day discharge is safe and feasible following ICD placement for primary prevention of SCD and hence a reduction in healthcare costs can be achieved by decreasing the length of hospital stay.
Features of lateral cephalograms associated with difficult laryngoscopy in Japanese children undergoing oral and maxillofacial surgery
Authors: Kohjitani Atsushi , Miyawaki Takuya , Miyawaki Shouichi , Nakamura Norifumi , Iwase Yoko , Nishihara Kazuhide , Ohno Sachi , Shimada Masahiko , Sugiyama Kazuna
Published: April 2013

Background

Difficult laryngoscopy and tracheal intubation are occasionally encountered in children with congenital anomalies or micrognathia. However, no study has elucidated anatomical etiology in relation to craniofacial development.

Methods

Two hundred ten patients aged 8 months–18 years were analyzed. We analyzed the lateral cephalograms of: (i) eight patients in whom laryngoscopy was anticipated as difficult before anesthesia and who were unable to be intubated by direct laryngoscopy and needed fiberoptic bronchoscopy (group A); (ii) 11 patients in whom laryngoscopy was anticipated as difficult before anesthesia but who were able to be intubated by direct laryngoscopy (group B); and (iii) 191 patients in whom laryngoscopy was anticipated as easy before anesthesia and was actually found to be easy (group C). Eight cephalometric parameters were measured and age–parameter relationships were plotted. Logistic regression analysis was performed to characterize group A children for each of the cephalometric variables.

Results

Apparently insufficient growth of the mandible was observed in the group A children. Furthermore, the group A children of aged <4 years had undeveloped maxilla, longer mandibular plane–hyoid distances (≥1.3 cm), and deeper depth of the oropharynx; those of aged ≥4 years showed increased inclination of the mandible (sella–nasion plane to mandibular plane angle of ≥46.5°).

Conclusions

Difficult laryngoscopy and tracheal intubation are expected in children aged <4 years with lower‐positioned hyoid bone caused by caudal larynx as well as undeveloped maxilla and mandible, and in those aged ≥4 years with increased inclination of the mandible as well as undeveloped mandible.
A closed‐form solution for steady‐state coupled phloem/xylem flow using the Lambert‐W function
Authors: HALL A. J. , MINCHIN P. E. H.
Published: April 2013

A closed‐form solution for steady‐state coupled phloem/xylem flow is presented. This incorporates the basic Münch flow model of phloem transport, the cohesion model of xylem flow, and local variation in the xylem water potential and lateral water flow along the transport pathway. Use of the Lambert‐W function allows this solution to be obtained under much more general and realistic conditions than has previously been possible. Variation in phloem resistance (i.e. viscosity) with solute concentration, and deviations from the Van't Hoff expression for osmotic potential are included. It is shown that the model predictions match those of the equilibrium solution of a numerical time‐dependent model based upon the same mechanistic assumptions. The effect of xylem flow upon phloem flow can readily be calculated, which has not been possible in any previous analytical model. It is also shown how this new analytical solution can handle multiple sources and sinks within a complex architecture, and can describe competition between sinks. The model provides new insights into Münch flow by explicitly including interactions with xylem flow and water potential in the closed‐form solution, and is expected to be useful as a component part of larger numerical models of entire plants.
Pediatric malpractice: An overview of Turkey
Authors: Ozkaya Nesrin , Ozkaya Halit , Ozkara Erdem
Published: April 2013

Background

The objective of this study was to evaluate juridical and medical responsibilities of health‐care professionals accused of malpractice in Turkey while they care for patients under the age of 18.

Methods

The cases sent to the Council of Forensic Medicine Institution by the courts, including claims of medical malpractice (n = 1458), in order to get an expert opinion between 2002 and 2006, were examined retrospectively. Cases of negligence by health‐care professionals who gave medical care to children between the ages of 0 and 18 were evaluated statistically.

Results

There was medical malpractice in 28.8% of the cases; and 68.2% of the cases were male. A large proportion of the cases were found to occur in emergency departments; and 57.9% of injuries resulted in death. The specialist doctors seemed to be sued or to be accountable for compensation more frequently than the general practitioners. This can be attributed to the fact that they perform more complicated medical interventions.

Conclusions

Courts specializing in health legislation may be useful to decrease the time consumed by trials. These specialized courts will also support logical judgment. In addition, postgraduate education is useful in reducing malpractice claims.
How to Measure Prenatal Stress? A Systematic Review of Psychometric Instruments to Assess Psychosocial Stress during Pregnancy
Authors: Nast Irina , Bolten Margarete , Meinlschmidt Gunther , Hellhammer Dirk H.
Published: April 2013

Background

A growing body of literature documents associations of maternal psychosocial stress during pregnancy with fetal, infant and child behaviour and development. However, findings across studies are often inconsistent, which may in part be due to differences in stress definitions and assessments.

Methods

We systematically reviewed methods applied to assess maternal psychosocial stress during pregnancy in studies looking at associations with biobehavioural outcomes in the offspring. A systematic literature search was performed on Web of Science and PubMed for the time period between January 1999 and October 2009. Psychometric instruments assessing maternal psychosocial stress during pregnancy were identified and described if data on psychometric properties were available.

Results

We identified 115 publications that assessed psychosocial stress during pregnancy with validated methods. These publications applied overall 43 different instruments assessing constructs falling under seven categories, ordered according to their frequency of use: anxiety, depression, daily hassles, aspects of psychological symptomatology (not reduced to anxiety or depression), life events, specific socio‐environmental stressors and stress related to pregnancy and parenting. If available, we provide information on validity and reliability of the instruments for samples of pregnant women.

Conclusions

Within the ‘prenatal stress’ research, a broad range of instruments is applied to assess psychosocial stress during pregnancy. Prenatal stress research should take into consideration that the variety of methods in use might hamper the comparability of stress research results. In each category of stress constructs, one instrument with good psychometric properties in pregnant women is highlighted as the best currently available measure.
Association betweenP3 event‐related potential amplitude and externalizing disorders: A time‐domain and time‐frequency investigation of 29‐year‐old adults
Authors: Yoon Henry H. , Malone Stephen M. , Burwell Scott J. , Bernat Edward M. , Iacono William G.
Published: April 2013

This study determined whether time‐domainP3 amplitude and time‐frequency principal component (TF‐PC) reductions are present in adulthood (age 29) when participants have largely passed through the age of heaviest substance misuse. Participants were assessed from age 17 through 29 for lifetime externalizing (EXT) disorders.EEGcomparisons from three topographic regions were examined forP3 amplitude andTF‐PCsat delta and theta frequency ranges. SignificantP3 amplitude reductions were found in those withEXTfor both regional and site‐Pz analyses, with stronger effects observed the greater theEXTcomorbidity. Reductions were also observed in all eightTF‐PCsextracted, with a delta component yielding frontal effects not apparent in the time domain. Overall, results suggest that these brain measures continue, at age 29, to provide effective indices ofEXTthat potentially tap a neural substrate related to behavioral disinhibition.
Other Aspects of BSE Issues in East Asian Countries
Authors: Sekizawa Jun
Published: April 2013

Scientific risk estimates of BSE can be the same internationally; however, socioeconomic backgrounds, such as food supply (e.g., beef import status) and dietary life, are different between East Asian countries (i.e., in this article, Japan, Korea, and Taiwan) and Western countries, which may account for differences in risk perception of people. Since political and social backgrounds also differ among these East Asian countries, they will also influence people's attitudes toward food safety. Psychological factors such as “dread” and the “unknown” are considered to be important in risk perception, but socioeconomic, and in some cases political, situations (e.g., attitudes of politicians and political pressures in trade) may strongly influence the perception and acceptance of various risks by citizens. With regard to the BSE issues, latter aspects may contribute a lot to risk perception, but have not been examined in depth until now. Although protection of health is the key element to food safety, sometimes business factors can overwhelm safety issues in international trade. Appropriate risk governance in food safety issues, such as BSE, can be attained not only through application of outputs of scientific assessment, but also through deliberation of various aspects, that may have strong influence on people's risk perception, and improved communication among stakeholders and also among countries.
Subcoracoid Ganglion Cyst in an Adolescent
Authors: Chou Justin , Hirner Marc
Published: April 2013

Ganglion cyst of the subcoracoid location around the shoulder is uncommon. Most cysts of the shoulder are described in the adult population. No previous English literature has reported symptomatic cyst of this location in children. Ganglion of the shoulder can produce various symptoms from mechanical compression such as pain, limited motion and neuropathic weakness.

A thirteen-year-old patient presented with chronic pain of his coracoid process and limited shoulder motion in forward flexion and rotation. Ultrasound scan demonstrated a cystic mass at the base of the coracoid process. MRI suggested this mass consistent with ganglion cyst on T2-weighted images. No labral pathology was found on MRI and diagnostic arthroscopy.

The patient underwent arthroscopic exploration and open excisional biopsy. No associated intra-articular pathology was found. Through a deltopectoral approach, a cystic mass was directly identified and excised at the base of the coracoid process and subsequently. Histology confirmed the diagnosis of a ganglion cyst. Postoperatively the symptoms have resolved with improved function.

A rare case of ganglion cyst of the subcoracoid location in this young age group was reported. Chronic shoulder pain with impingement can be from mechanical compression of a ganglion cyst. Complete surgical excision is important to prevent recurrence.
Isolated Rupture of the Separate Insertion of the Short Head of Biceps on the Radial Tuberosity: Ultrasound and Magnetic Resonance Imaging Diagnosis with Successful Surgical Treatment
Authors: Witney-Lagen Caroline , Kothapalli Swathy , Robinson Richard , Venkateswaran Balachandran
Published: April 2013

We report a case of isolated rupture of the separate insertion of the short head of biceps on the radial tuberosity. This case occurred in a 52-year-old male fitness instructor who lifted a heavy weight. The patient presented with pain, bruising of the anterior elbow and weakness of elbow flexion. There was no bunching of the distal biceps and the hook test was normal. The rupture and location of the tendon ends was identified by several transverse and longitudinal ultrasound images and then definitively confirmed by magnetic resonance imaging. The rupture was surgically repaired, resulting in good functional ability. Early detection is vitally important for optimal management, especially when functional disability is present.
An empirical model of subcritical bedform migration
Authors: Martin Lin Chan‐Yi , Venditti Jeremy G.
Published: April 2013

The ability to predict bedform migration in rivers is critical for estimating bed material load, yet there is no relation for predicting bedform migration (downstream translation) that covers the full range of conditions under which subcritical bedforms develop. Here, the relation between bedform migration rates and transport stage is explored using a field and several flume data sets. Transport stage is defined as the non‐dimensional Shields stress divided by its value at the threshold for sediment entrainment. Statistically significant positive correlations between both ripple and dune migration rates and transport stage are found. Stratification of the data by the flow depth to grain‐size ratio improved the amount of variability in migration rates that was explained by transport stage toca70%. As transport stage increases for a given depth to grain‐size ratio, migration rates increase. For a given transport stage, the migration rate increases as the flow depth to grain‐size ratio gets smaller. In coarser sediment, bedforms move faster than in finer sediment at the same transport stage. Normalization of dune migration rates by the settling velocity of bed sediment partially collapses the data. Given the large amount of variability that arises from combining data sets from different sources, using different equipment, the partial collapse is remarkable and warrants further testing in the laboratory and field.
Effects of whole‐body cryotherapy on recovery after hamstring damaging exercise: A crossover study
Authors: Fonda B. , Sarabon N.
Published: April 2013

The purpose of this study was to examine the effects of whole‐body cryotherapy (WBC) on biochemical, pain, and performance parameters during the 5‐day recovery period after damaging exercise for hamstrings. Participants completed a bout of damaging exercise for the hamstring muscles on two separate occasions (control and experimental condition) separated by 10 weeks. During the control condition, subjects received no treatment after the damaging exercise. The experimental condition consisted of WBC everyday during the recovery period. WBC included single 3‐min daily exposures to low temperatures (−140 to −195 °C) in the cryo‐cabin. During the recovery period, subjects were tested for biochemical markers, perceived pain sensation, and physical performance (squat jump, counter movement jump, maximal isometric torque production, and maximally explosive isometric torque production). Majority of the observed variables showed statistically significant time effects (P < 0.05) in control group, which indicates the presence of muscle damage. Significant interaction between the control and WBC condition was evident for the rate of torque development (P < 0.05). Pain measures substantially differed between the WBC and the control condition after the exercise. Results of this study are not completely supportive of the use of WBC for recovery enhancement after strenuous training.
Low hemorrhage‐related mortality in trauma patients in a Level I trauma center employing transfusion packages and early thromboelastography‐directed hemostatic resuscitation with plasma and platelets
Authors: Johansson Pär I. , Sørensen Anne Marie , Larsen Claus F. , Windeløv Nis A. , Stensballe Jakob , Perner Anders , Rasmussen Lars S. , Ostrowski Sisse R.
Published: April 2013

Background

Hemorrhage accounts for most preventable trauma deaths, but still the optimal strategy for hemostatic resuscitation remains debated.

Study Design and Methods

This was a prospective study of adult trauma patients admitted to a Level I trauma center. Demography, Injury Severity Score (ISS), transfusion therapy, and mortality were registered. Hemostatic resuscitation was based on a massive transfusion protocol encompassing transfusion packages and thromboelastography (TEG)‐guided therapy.

Results

A total of 182 patients were included (75% males, median age 43 years, ISS of 17, 92% with blunt trauma). Overall 28‐day mortality was 12% with causes of death being exsanguinations (14%), traumatic brain injury (72%, two‐thirds expiring within 24 hr), and other (14%). One‐fourth, 16 and 15% of the patients, received red blood cells (RBCs), plasma, or platelets (PLTs) within 2 hours from admission and 68, 71, and 75%, respectively, of patients transfused within 24 hours received the respective blood products within the first 2 hours. In patients transfused within 24 hours, the median number of blood products at 2 hours was 5 units of RBCs, 5 units of plasma, and 2 units of PLT concentrates. Nonsurvivors had lower clot strength by kaolin‐activated TEG and TEG functional fibrinogen and lower kaolin–tissue factor‐activated TEG α‐angle and lysis after 30 minutes compared to survivors. None of the TEG variables were independent predictors of massive transfusion or mortality.

Conclusion

Three‐fourths of the patients transfused with plasma or PLTs within 24 hours received these in the first 2 hours. Hemorrhage caused 14% of the deaths. We introduced transfusion packages and early TEG‐directed hemostatic resuscitation at our hospital 10 years ago and this may have contributed to reducing hemorrhagic trauma deaths.
Evaluation of selective screening of donors for antibody to Trypanosoma cruzi: seroprevalence of donors who answer “no” to risk questions
Authors: O'Brien Sheila F. , Scalia Vito , Goldman Mindy , Fan Wenli , Yi Qi‐Long , Huang Mary , Ndao Momar , Fearon Margaret A.
Published: April 2013

Background

Selective testing of donors for Trypanosoma cruzi infection relies on identification of at‐risk donors with screening questions. Using risk modeling and a seroprevalence study, we evaluated the risk of questions failing to identify T. cruzi antibody–positive donors.

Study Design and Methods

The rate of donors with unreported risk was estimated by a telephone survey of 2677 donors who answered “no” to risk questions. The number of T. cruzi antibody–positive donors missed by risk questions was estimated from the product of this rate and the selective testing T. cruzi antibody–positive rate. The 95% confidence interval (CI) was estimated by Monte Carlo simulation. To test the model, 60,132 donors were tested for T. cruzi antibody (26% of donors in selected regions, Phase I). In Winnipeg, Manitoba, the highest‐risk region, 26,915 donors were tested (92.5% of donors, Phase II).

Results

In the telephone survey, 21 (0.8%) donors reported risk factors that would have identified them for selective testing. Seven were born in Mexico or Central or South America, five had travel risk, and nine had mother or maternal grandmother risk. The 95% CI for predicted number of T. cruzi antibody–positive donors answering “no” to risk questions was 0.71 to 4.38. In Phase I, one Winnipeg donor confirmed positive but had answered risk questions correctly. No other positive donations were identified.

Conclusion

The estimated risk of T. cruzi–positive donors who answer “no” to risk questions is low and is confirmed by the seroprevalence among these donors.
Epitaxial NiInGaAs formed by solid state reaction on In0.53Ga0.47As: Structural and chemical study
Authors: Shekhter Pini , Mehari Shlomo , Ritter Dan , Eizenberg Moshe
Published: April 2013

Thin epitaxial layers of NiInGaAs formed by solid state reaction of Ni on (100) In0.53Ga0.47As are used as metal source and drain regions for In0.53Ga0.47As metal oxide field effect transistors. Here, the authors present a structural and chemical analysis of this phase. The stoichiometry of the layer was determined as Ni2In0.53Ga0.47As. Transmission electron microscopy revealed an abrupt interface and a detailed x-ray diffraction analysis showed that the layer is of a hexagonal lattice, which grows epitaxially with the orientation relations of {100}InGaAs||{100}NiInGaAs; ⟨011¯⟩InGaAs||[001]NiInGaAs. Only one domain can be observed in this epitaxial growth. Understanding the structure of these layers is a crucial step not only in their incorporation into InGaAs based devices but also a step toward novel devices.
PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria
Authors: Chen Yun , Dorn Gerald W.
Published: April 2013

Where Parkin Parks

Damaged mitochondria are removed from cells in a process known as mitophagy. Failure of this quality-control mechanism contributes to Parkinson's disease. When damaged mitochondria lose membrane depolarization, the protein kinase, PINK1, accumulates on the mitochondrial surface, recruits Parkin, and promotes mitophagy.
Chen and Dorn
(p.
471
) describe another component of this process, mitofusin 2, which appears to function as the receptor for Parkin on the surface of damaged mitochondria.
Vaterite Crystals Contain Two Interspersed Crystal Structures
Authors: Kabalah-Amitai Lee , Mayzel Boaz , Kauffmann Yaron , Fitch Andrew N. , Bloch Leonid , Gilbert Pupa U. P. A. , Pokroy Boaz
Published: April 2013

Double Vision

Vaterite is the least stable form of anhydrous crystalline calcium carbonate. While rarely found in geological contexts, it is an important biological precursor and occurs as a minor component in the shells of some organisms. The crystal structure of vaterite has long been debated with no model able to explain all the experimentally observed diffraction spots.

Kabalah-Amitai
et al.

(p.
454
) show that vaterite contains two coexisting crystallographic structures that form a pseudo-single crystal.
Population Growth in a Wild Bird Is Buffered Against Phenological Mismatch
Authors: Reed Thomas E. , Grøtan Vidar , Jenouvrier Stephanie , Sæther Bernt-Erik , Visser Marcel E.
Published: April 2013

Balancing Act

Life cycles are strongly influenced by seasonal and interannual environmental and climate events. Such phenological timings are likely to shift as our climate changes, but species exist in communities, and not all species can be expected to shift in concert.

Reed
et al.

(p.
488
) used long-term data on European great tits to reveal how the negative consequences of phenological mismatch can be buffered: Lower fitness in individuals subject to mismatch-driven reductions of food availability was balanced by reductions in competition. Thus, overall, the population is resilient and has not declined.
A Massive Pulsar in a Compact Relativistic Binary
Authors: Antoniadis John , Freire Paulo C. C. , Wex Norbert , Tauris Thomas M. , Lynch Ryan S. , van Kerkwijk Marten H. , Kramer Michael , Bassa Cees , Dhillon Vik S. , Driebe Thomas , Hessels Jason W. T. , Kaspi Victoria M. , Kondratiev Vladislav I. , Langer Norbert , Marsh Thomas R. , McLaughlin Maura A. , Pennucci Timothy T. , Ransom Scott M. , Stairs Ingrid H. , van Leeuwen Joeri , Verbiest Joris P. W. , Whelan David G.
Published: April 2013

Pulsar Tests Gravity

Because of their extremely high densities, massive neutron stars can be used to test gravity. Based on spectroscopy of its white dwarf companion,

Antoniadis
et al.

(p.
448
) identified a millisecond pulsar as a neutron star twice as heavy as the Sun. The observed binary's orbital decay is consistent with that predicted by general relativity, ruling out previously untested strong-field phenomena predicted by alternative theories. The binary system has a peculiar combination of properties and poses a challenge to our understanding of stellar evolution.
Early Ceremonial Constructions at Ceibal, Guatemala, and the Origins of Lowland Maya Civilization
Authors: Inomata Takeshi , Triadan Daniela , Aoyama Kazuo , Castillo Victor , Yonenobu Hitoshi
Published: April 2013

Early Mayan Architects

Lowland Mayan civilizations began to construct dramatic pyramids beginning about 900 BCE. The cultural origins of these civilizations have been uncertain, particularly the connection to earlier Olmec cultures along the Gulf of Mexico.

Inomata
et al.

(p.
467
; see the cover; see the News story by
Pringle
) describe excavations and extensive radiocarbon dating at the early Mayan city of Ceibal in Guatamala. The site shows incipient plaza and pyramid construction beginning before those seen in the lowlands or Olmec areas, suggesting a broader cultural exchange through to the Pacific Coast as Mayan cultures evolved.
A Circuitous Route to Noncoding RNA
Authors: Wilusz Jeremy E. , Sharp Phillip A.
Published: April 2013

A class of circular RNAs that regulates microRNAs is abundant in mammalian cells.
Despite Large Research Effort, H7N9 Continues to Baffle
Authors: Hvistendahl Mara , Normile Dennis , Cohen Jon
Published: April 2013

Nearly a month after the first reported cases of people infected with the bird flu virus, puzzles remain about how it made the jump to humans, how to prevent transmission, and how frequently an infection causes disease.
Evaluation of Regulated Delayed Attenuation Strategies for Salmonella enterica Serovar Typhi Vaccine Vectors in Neonatal and Infant Mice
Authors: Shi Huoying , Wang Shifeng , Curtiss Roy
Published: April 2013

We developed regulated delayed attenuation strategies forSalmonellavaccine vectors. In this study, we evaluated the combination of these strategies in recombinant attenuatedSalmonella entericaserovar Typhi andSalmonella entericaserovar Typhimurium vaccine vectors with similar genetic backgroundsin vitroandin vivo. Our goal is to develop a vaccine to preventStreptococcus pneumoniaeinfection in newborns; thus, all strains delivered a pneumococcal antigen PspA and the impact of maternal antibodies was evaluated. The results showed that all strains with the regulated delayed attenuated phenotype (RDAP) displayed an invasive ability stronger than that of theS.Typhi vaccine strain, Ty21a, but weaker than that of their corresponding wild-type parental strains. The survival curves of different RDAP vaccine vectorsin vitroandin vivoexhibited diverse regulated delayed attenuation kinetics, which was different fromS.Typhi Ty21a and the wild-type parental strains. Under the influence of maternal antibody, the persistence of theS.Typhimurium RDAP strain displayed a regulated delayed attenuation trend in nasal lymphoid tissue (NALT), lung, and Peyer's patches, while the persistence ofS.Typhi RDAP strains followed the curve only in NALT. The bacterial loads ofS.Typhi RDAP strains were lower in NALT, lung, and Peyer's patches in mice born to immune mothers than in those born to naive mothers. In accordance with these results, RDAP vaccine strains induced high titers of IgG antibodies against PspA and againstSalmonellalipopolysaccharides. Immunization of mothers withS.Typhi RDAP strains enhanced the level of vaginal mucosal IgA, gamma interferon (IFN-γ), and interleukin 4 (IL-4) and resulted in a higher level of protection againstS. pneumoniaechallenge.
Transplantation-Associated Long-Term Immunosuppression Promotes Oral Colonization by Potentially Opportunistic Pathogens without Impacting Other Members of the Salivary Bacteriome
Authors: Diaz Patricia I. , Hong Bo-Young , Frias-Lopez Jorge , Dupuy Amanda K. , Angeloni Mark , Abusleme Loreto , Terzi Evimaria , Ioannidou Effie , Strausbaugh Linda D. , Dongari-Bagtzoglou Anna
Published: April 2013

Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic
Gammaproteobacteria
such as
Klebsiella pneumoniae
,
Pseudomonas fluorescens
,
Acinetobacter
species,
Vibrio
species,
Enterobacteriaceae
species, and the genera
Acinetobacter
and
Klebsiella
. Transplant subjects also had increased proportions of
Pseudomonas aeruginosa
,
Acinetobacter
species,
Enterobacteriaceae
species, and
Enterococcus faecalis
, among other OTUs, while genera with increased proportions included
Klebsiella
,
Acinetobacter
,
Staphylococcus
, and
Enterococcus
. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome.
Molecular and Antimicrobial Susceptibility Analyses Distinguish Clinical from Bovine Escherichia coli O157 Strains
Authors: Vidovic Sinisa , Tsoi Sarah , Medihala Prabhakara , Liu Juxin , Wylie John L. , Levett Paul N. , Korber Darren R.
Published: April 2013

A population-based study combining (i) antimicrobial, (ii) genetic, and (iii) virulence analyses with molecular evolutionary analyses revealed segregative characteristics distinguishing human clinical and bovine
Escherichia coli
O157 strains from western Canada. Human (
n
= 50) and bovine (
n
= 50) strains of
E. coli
O157 were collected from Saskatchewan and Manitoba in 2006 and were analyzed by using the six-marker lineage-specific polymorphism assay (LSPA6), antimicrobial susceptibility analysis, the colicin assay, plasmid and virulence profiling including the
eae
,
ehxA
,
espA
,
iha
,
stx
1
,
stx
2
,
stx
2c
,
stx
2d
,
stx
2d-activatable
,
stx
2e
, and
stx
2f
virulence-associated genes, and structure analyses. Multivariate logistic regression and Fisher's exact test strongly suggested that antimicrobial susceptibility was the most distinctive characteristic (
P
= 0.00487) associated with human strains. Among all genetic, virulence, and antimicrobial determinants, resistance to tetracycline (
P
< 0.000) and to sulfisoxazole (
P
< 0.009) were the most strongly associated segregative characteristics of bovine
E. coli
O157 strains. Among 11 virulence-associated genes,
stx
2c
showed the strongest association with
E. coli
O157 strains of bovine origin. LSPA6 genotyping showed the dominance of the lineage I genotype among clinical (90%) and bovine (70%) strains, indicating the importance of lineage I in O157 epidemiology and ecology. Population structure analysis revealed that the more-diverse bovine strains came from a unique group of strains characterized by a high degree of antimicrobial resistance and high frequencies of lineage II genotypes and
stx
2c
variants. These findings imply that antimicrobial resistance generated among bovine strains of
E. coli
O157 has a large impact on the population of this human pathogen.
Detection of Specific Antibodies against Tembusu Virus in Ducks by Use of an E Protein-Based Enzyme-Linked Immunosorbent Assay
Authors: Yin Xiuchen , Lv Rang , Chen Xiaodan , Liu Ming , Hua Ronghong , Zhang Yun
Published: April 2013

We developed an enzyme-linked immunosorbent assay (ELISA) using eukaryotically expressed E protein as the antigen (termed E-ELISA) to detect antibodies to tembusu virus (TMUV) in ducks. The E-ELISA did not react with antisera to other known pathogens, indicating the E protein is specific for recognizing anti-TMUV antibodies. Compared to the serum neutralization test, the specificity and sensitivity of the E-ELISA was 93.2 and 97.8%, respectively. Therefore, this E-ELISA is a sensitive and rapid method for detecting antibodies against TMUV in ducks.
Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Testing Susceptible to Cefepime by Reference Methods
Authors: Picão Renata C. , Jones Ronald N. , Mendes Rodrigo E. , Castanheira Mariana
Published: April 2013

β-Lactam susceptibility of 499
Klebsiella pneumoniae
carbapenemase (KPC)-producing
Enterobacteriaceae
, determined by reference broth microdilution, demonstrated that 14.4% of isolates were categorized as cefepime susceptible according to current CLSI breakpoints. Ceftazidime- and meropenem-susceptible isolates were also observed (2.6 and 3.0%, respectively). Cefepime-susceptible KPC-producing isolates may confuse laboratory staff and clinicians in their therapeutic choices.
Molecular Characterization of Endocarditis-Associated Staphylococcus aureus
Authors: Nethercott Cara , Mabbett Amanda N. , Totsika Makrina , Peters Paul , Ortiz Juan C. , Nimmo Graeme R. , Coombs Geoffrey W. , Walker Mark J. , Schembri Mark A.
Published: April 2013

Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves.
Staphylococcus aureus
is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST),
spa
typing, and virulence gene microarrays are frequently used to classify
S. aureus
clinical isolates. This study examined the utility of these typing tools to investigate
S. aureus
epidemiology associated with IE. Ninety-seven
S. aureus
isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the
S. aureus
population by eBURST analysis. The
spa
type of all isolates was also determined. A null model was used to determine correlations of IE with CC and
spa
type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and
spa
type t160 were significantly associated with IE
S. aureus
. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST,
spa
typing, and microarray analysis are promising tools for monitoring
S. aureus
epidemiology associated with IE. Further research to determine a role for the
S. aureus
IE-associated virulence genes identified in this study is warranted.
Monoclonal Antibodies Combined with Adenovirus-Vectored Interferon Significantly Extend the Treatment Window in Ebola Virus-Infected Guinea Pigs
Authors: Qiu Xiangguo , Wong Gary , Fernando Lisa , Ennis Jane , Turner Jeffrey D. , Alimonti Judie B. , Yao Xiaojian , Kobinger Gary P.
Published: April 2013

Monoclonal antibodies (MAbs) are currently a promising treatment strategy against Ebola virus infection. This study combined MAbs with an adenovirus-vectored interferon (DEF201) to evaluate the efficacy in guinea pigs and extend the treatment window obtained with MAbs alone. Initiating the combination therapy at 3 days postinfection (d.p.i.) provided 100% survival, a significant improvement over survival with either treatment alone. The administration of DEF201 within 2 d.p.i. permits later MAb use, with protective efficacy observed up to 8 d.p.i.
Adoptive Transfer of Lymphocytes Isolated from Simian Immunodeficiency Virus SIVmac239Δnef-Vaccinated Macaques Does Not Affect Acute-Phase Viral Loads but May Reduce Chronic-Phase Viral Loads in Major Histocompatibility Complex-Matched Recipients
Authors: Greene Justin M. , Lhost Jennifer J. , Hines Paul J. , Scarlotta Matthew , Harris Max , Burwitz Benjamin J. , Budde Melisa L. , Dudley Dawn M. , Pham Ngoc , Cain Brian , Mac Nair Caitlin E. , Weiker Madelyn K. , O'Connor Shelby L. , Friedrich Thomas C. , O'Connor David H.
Published: April 2013

The live attenuated simian immunodeficiency virus (SIV) SIVmac239Δnef is the most effective SIV/human immunodeficiency virus (HIV) vaccine in preclinical testing. An understanding of the mechanisms responsible for protection may provide important insights for the development of HIV vaccines. Leveraging the uniquely restricted genetic diversity of Mauritian cynomolgus macaques, we performed adoptive transfers between major histocompatibility complex (MHC)-matched animals to assess the role of cellular immunity in SIVmac239Δnef protection. We vaccinated and mock vaccinated donor macaques and then harvested between 1.25 × 10
9
and 3.0 × 10
9
mononuclear cells from multiple tissues for transfer into 12 naive recipients, followed by challenge with pathogenic SIVmac239. Fluorescently labeled donor cells were detectable for at least 7 days posttransfer and trafficked to multiple tissues, including lung, lymph nodes, and other mucosal tissues. There was no difference between recipient macaques' peak or postpeak plasma viral loads. A very modest difference in viral loads during the chronic phase between vaccinated animal cell recipients and mock-vaccinated animal cell recipients did not reach significance (
P
= 0.12). Interestingly, the SIVmac239 challenge virus accumulated escape mutations more rapidly in animals that received cells from vaccinated donors. These results may suggest that adoptive transfers influenced the course of infection despite the lack of significant differences in the viral loads among animals that received cells from vaccinated and mock-vaccinated donor animals.
Human Papillomavirus Types 16, 18, and 31 Share Similar Endocytic Requirements for Entry
Authors: Spoden Gilles , Kühling Lena , Cordes Nicole , Frenzel Bettina , Sapp Martin , Boller Klaus , Florin Luise , Schelhaas Mario
Published: April 2013

Human papillomavirus type 18 (HPV18), one of the HPVs with malignant potential, enters cells by an unknown endocytic mechanism. The key cellular requirements for HPV18 endocytosis were tested in comparison to those for HPV16 and -31 endocytoses. HPV18 (like HPV16 and -31) entry was independent of clathrin, caveolin, dynamin, and lipid rafts but required actin polymerization and tetraspanin CD151, and the viruses were routed to the same LAMP-1-positive compartment. Hence, the viruses shared similar cellular requirements for endocytic entry.
Modulation of GB Virus B RNA Abundance by MicroRNA-122: Dependence on and Escape from MicroRNA-122 Restriction
Authors: Sagan Selena M. , Sarnow Peter , Wilson Joyce A.
Published: April 2013

Hepatitis C virus (HCV) RNA forms an unusual interaction with human microRNA-122 (miR-122) that promotes viral RNA accumulation in cultured human liver cells and in the livers of infected chimpanzees. GB virus B (GBV-B) is a hepatotropic virus and close relative of HCV. Thus, GBV-B has been used as a surrogate system to study HCV amplification in cultured cells and in infected tamarins. It was discovered that the 5′-terminal sequences of GBV-B RNA, like HCV RNA, forms an Argonaute 2-mediated complex with two miR-122 molecules that are essential for accumulation of GBV-B subgenomic replicon RNA. However, sequences in miR-122 that anneal to each viral RNA genome were different, suggesting distinct overall structural features in HCV:miR-122 and GBV-B:miR-122 complexes. Surprisingly, a deletion that removed both miR-122 binding sites from the subgenomic GBV-B RNAs rendered viral RNA amplification independent from miR-122 and Argonaute 2. This finding suggests that structural features at the end of the viral genome dictate whether miR-122 is required to aid in maintaining viral RNA abundance.
Toll-Like Receptor 7 Inhibits Early Acute Retroviral Infection through Rapid Lymphocyte Responses
Authors: Browne Edward P.
Published: April 2013

Early events during retroviral infection play a critical role in determining the course of infection and pathogenesis, but the mechanisms that regulate this phase of infection are poorly understood. Toll-like receptor 7 (TLR7) is required for promoting germinal center reactions and virus-specific neutralizing antibodies at later time points postinfection, but TLR7's role in early acute infection has not been determined. By infecting TLR7-deficient mice with a retroviral pathogen, Friend virus (FV), I determined that TLR7 potently inhibits retroviral replication during the first 5 days of infection and is required for rapid secretion of virus-specific IgM and interleukin-10 (IL-10) in response to infection. Although the IgM response was nonneutralizing, plasmas from wild-type mice but not TLR7-deficient mice inhibited FV replication when passively transferred to infected mice, suggesting an indirect mechanism of antibody function. Interestingly, IL-10 was secreted primarily by CD4 T cells, and IL-10-deficient mice also exhibited accelerated early virus spread, demonstrating that this response inhibits acute infection. Surprisingly, TLR7-deficient mice exhibited normal or elevated secretion of proinflammatory cytokines during acute infection, revealing the existence of a TLR7-independent retrovirus-sensing pathway that drives inflammatory cytokine secretion. Together, these results establish a previously unappreciated role for lymphocytes in mediating rapid TLR7-dependent inhibition of early retroviral infection through nonneutralizing IgM and IL-10.
Foamy Virus Gag p71-p68 Cleavage Is Required for Template Switch of the Reverse Transcriptase
Authors: Spannaus Ralf , Schneider Anna , Hartl Maximilian J. , Wöhrl Birgitta M. , Bodem Jochen
Published: April 2013

In contrast to orthoretroviruses, processing of foamy viral p71 Gag is limited to a single cleavage site. Nevertheless, Gag maturation is essential for infectivity, but deletion of p3 results in a modest drop in infectivity. Here, we show that Gag processing of p71 to p68 and p3 is essential for full-length cDNA synthesis, while inactivation of Gag cleavage results in cDNAs containing only the RU5 region; cDNAs encompassing the U3 region were almost undetectable.