bluuebunny/crossref_metadata_2025 huggingface dataset:
NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in
Nicotiana benthamiana
Authors: Saur Isabel M. L. , Kadota Yasuhiro , Sklenar Jan , Holton Nicholas J. , Smakowska Elwira , Belkhadir Youssef , Zipfel Cyril , Rathjen John P.
Published: March 2016

Significance

Plants detect pathogens by surface-localized receptors. Few such receptors are known. The coreceptor BRI1-ASSOCIATED KINASE 1 (BAK1) is a frequent member of activated receptor complexes. The proteomics strategy described here uses BAK1 as molecular bait to identify potential receptors that are specifically activated by pathogen components. We demonstrate this approach by identifying
Nicotiana benthamiana
RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). We show that NbCSPR is required for immune responses initiated by the bacterial cold shock protein, confers age-dependent immunity against bacteria, and restricts the transformation of
N. benthamiana
cells by
Agrobacterium
. Manipulation of this gene will provide new options for disease control and genetic transformation of crop species.
Courtly Connections: Anthony Sherley’sRelation of his trauels(1613) in a Global Context
Authors: Şahin Kaya , Schleck Julia
Published: March 2016

This article revisits Anthony Sherley’sRelation of his trauels into Persia(1613), reading the text within the larger context of early modern Eurasia. It highlights the ways in which at least one European traveler sought and found not alterity, but commensurable structures, social roles, political ideologies, and personal motivations in the Islamic polities to the east and emphasized these connections to his European readers. Furthermore, in making the case that Sherley’s narrative is informed by local actors in Safavid Persia, it maintains that a certain level of Eastern knowledge is present within Western texts from this period and awaits scholarly excavation.
Simulated single molecule microscopy with SMeagol
Authors: Lindén Martin , Ćurić Vladimir , Boucharin Alexis , Fange David , Elf Johan
Published: March 2016

Summary: SMeagol is a software tool to simulate highly realistic microscopy data based on spatial systems biology models, in order to facilitate development, validation and optimization of advanced analysis methods for live cell single molecule microscopy data.

Availability and implementation: SMeagol runs on Matlab R2014 and later, and uses compiled binaries in C for reaction–diffusion simulations. Documentation, source code and binaries for Mac OS, Windows and Ubuntu Linux can be downloaded from http://smeagol.sourceforge.net.

Contact:  johan.elf@icm.uu.se

Supplementary information: Supplementary data are available at Bioinformatics online.
Persistent Catechol-O-methyltransferase–dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors
Authors: Ciszek Brittney P. , O’Buckley Sandra C. , Nackley Andrea G.
Published: March 2016

AbstractAbstract

In rats, sustained administration of a catecholamine-O-methyltransferase inhibitor produces hypersensitivity to mechanical and thermal stimuli, which is prevented by peripheral, but not spinal or supraspinal, administration of β-adrenoceptor antagonists, suggesting a peripheral site of action.

Supplemental Digital Content is available in the text.

Background

Patients with chronic pain disorders exhibit increased levels of catecholamines alongside diminished activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. The authors found that acute pharmacologic inhibition of COMT in rodents produces hypersensitivity to mechanical and thermal stimuli via β-adrenergic receptor (βAR) activation. The contribution of distinct βAR populations to the development of persistent pain linked to abnormalities in catecholamine signaling requires further investigation.

Methods

Here, the authors sought to determine the contribution of peripheral, spinal, and supraspinal βARs to persistent COMT-dependent pain. They implanted osmotic pumps to deliver the COMT inhibitor OR486 (Tocris, USA) for 2 weeks. Behavioral responses to mechanical and thermal stimuli were evaluated before and every other day after pump implantation. The site of action was evaluated in adrenalectomized rats receiving sustained OR486 or in intact rats receiving sustained βAR antagonists peripherally, spinally, or supraspinally alongside OR486.

Results

The authors found that male (N = 6) and female (N = 6) rats receiving sustained OR486 exhibited decreased paw withdrawal thresholds (control 5.74 ± 0.24 vs. OR486 1.54 ± 0.08, mean ± SEM) and increased paw withdrawal frequency to mechanical stimuli (control 4.80 ± 0.22 vs. OR486 8.10 ± 0.13) and decreased paw withdrawal latency to thermal heat (control 9.69 ± 0.23 vs. OR486 5.91 ± 0.11). In contrast, adrenalectomized rats (N = 12) failed to develop OR486-induced hypersensitivity. Furthermore, peripheral (N = 9), but not spinal (N = 4) or supraspinal (N = 4), administration of the nonselective βAR antagonist propranolol, the β2AR antagonist ICI-118,511, or the β3AR antagonist SR59230A blocked the development of OR486-induced hypersensitivity.

Conclusions

Peripheral adrenergic input is necessary for the development of persistent COMT-dependent pain, and peripherally-acting βAR antagonists may benefit chronic pain patients.
Anticoagulant Effect of Sugammadex
Authors: Dirkmann Daniel , Britten Martin W. , Pauling Henning , Weidle Juliane , Volbracht Lothar , Görlinger Klaus , Peters Jürgen
Published: March 2016

AbstractAbstract

Sugammadex affects various coagulation assays by the binding of phospholipids by the cyclodextrin molecules, and this represents an in vitro artifact observed in commercial phospholipid-dependent assays such as the activated partial thromboplastin time.

Background

Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex’s impact on a panel of coagulation assays.

Methods

Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay.

Results

Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (−7%, P = 0.009; −7.8%, P < 0.0001; −6.9%, P < 0.0001; and −4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects.

Conclusion

Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.
49 Mathoura Road
Authors: Edwards Matthew L. , Waisel David B.
Published: March 2016

AbstractAbstract

Geoffrey Kaye, M.B.B.S. (1903 to 1986), was a prominent Australian anesthetist, researcher, and educator who envisioned that anesthesia practice in Australia would be comparable to European and American anesthesia practice during the 1940s and 1950s. Kaye’s close relationship with Francis Hoeffer McMechan, M.D., F.I.C.A. (1879 to 1939), which began when Kaye left a favorable impression on McMechan at a meeting of the Australasian Medical Congress in 1929, eventually led Kaye to establish an educational center for the Australian Society of Anaesthetists at 49 Mathoura Road, Toorak, Melbourne, Australia, in 1951. The center served as the “Scientific Headquarters” and the Australian Society of Anaesthetists’ official headquarters from 1951 to 1955. Although anesthesia’s recognition as a specialty was at the heart of the center, Kaye hoped that this “experiment in medical education”—equipped with a library, museum, laboratory, workshop, darkroom, and meeting space—would “bring anaesthetists of all lands together” in Australia. The lack of member participation in Kaye’s center, however, led Kaye to dissolve the center by 1955. Previous research has documented the history of Kaye’s center from correspondence between Kaye and influential American anesthesiologist Paul M. Wood, M.D. (1894 to 1953), from 1939 to 1955. Through letters Kaye sent to American anesthesiologist Paul M. Wood, M.D. (1894 to 1963), the authors see Kaye’s detailed plans, design, and intent for the center at 49 Mathoura Road. Comparisons of Kaye’s letters to Wood during the 1950s with his letters to Gwenifer Wilson, M.D., M.B.B.S. (1916 to 1988), during the 1980s illustrate a change in Kaye’s perceptions regarding the failure of the center.

Through letters written by Geoffrey Kaye to Paul Wood (1939 to 1955) and to Gwenifer Wilson (1981 to 1983), we present Kaye’s design and intent for his Australian Center of Excellence, and his views regarding its failure.
Comparison of Salter osteotomy and Tonnis lateral acetabuloplasty with simultaneous open reduction for the treatment of developmental dysplasia of the hip: midterm results
Authors: Bayhan Ilhan A. , Beng Kubilay , Yildirim Timur , Akpinar Evren , Ozcan Cagri , Yagmurlu Firat
Published: March 2016

The aim of this study was to compare the midterm clinical and radiological outcomes of the Salter osteotomy (SO) and Tonnis lateral acetabuloplasty (TLA) with concomitant open reduction for the treatment of developmental dysplasia of the hip. Twenty-five hips of 20 patients who underwent SO with open reduction and 26 hips of 23 patients who underwent TLA with open reduction were evaluated retrospectively. The average age of the patients at the time of the operation was 35.6 months in the SO and 36.6 months in the TLA group, without a statistically significant difference (P=0.836). The average follow-up times in the SO and TLA groups were 59.9 and 54.8 months, respectively (P=0.397). Preoperative (40.6° in the SO vs. 42.2° in the TLA, P=0.451) and last follow-up acetabular index (12° in the SO vs. 14° in the TLA, P=0.227) and center-edge angle measurements (30° in the SO vs. 26° in the TLA, P=0.069) did not show a statistically significant difference between the SO and TLA groups; however, early postoperative acetabular index improvement was better in the TLA group than in the SO group (21.2° in the SO vs. 17.2° in the TLA, P=0.014). According to the Severin grading system, both groups showed a similar number of good outcomes without a statistically significant difference (P=0.936). Clinical assessment on the basis of McKay’s criteria showed similar good and excellent outcomes (P=0.936). Both osteotomy techniques showed similar satisfactory outcomes for the treatment of DDH in patients older than 18 months of age.
The Open Bankart Repair for Traumatic Anterior Shoulder Instability in Teenage Athletes
Authors: Hatch Mark D. , Hennrikus William L.
Published: March 2016

Background:

Traumatic anterior shoulder instability from recurrent dislocations or subluxations is a debilitating problem for the teenage athlete. The risk of recurrent instability is high in this adolescent population. We performed a retrospective case series analysis of adolescent athletes with recurrent instability treated with open Bankart repair and evaluated functional outcomes as well as redislocation rates.

Methods:

The retrospective study included 21 teenage patients with Bankart lesions and recurrent anterior shoulder instability. There were 19 males (90%) and 2 females (10%) with an average age of 16 years (range, 14 to 18 y). Patients were evaluated based on Rowe and UCLA shoulder scores, return to previous level of sport, external rotation, and recurrence.

Results:

The average number of anchors used to repair the Bankart lesion was 3 (range, 2 to 5). One patient was lost to follow-up at 6 months after surgery. The remaining 20 patients all had at least 2-year follow-up. The recurrent instability rate was zero. In total, 100% of patients had an excellent result based on an average Rowe score of 96.5 points of 100 points (a score of 90 to 100 is an excellent result). In total, 100% of patients had good/excellent result based on an average UCLA shoulder score of 34 of 35 (a score >27 is a good/excellent result). At final follow-up, 7 patients (34%) had lost an average of 11 degrees of external rotation (range, 5 to 20 degrees) on the injured shoulder with the arm at the side compared with the noninjured shoulder.

Conclusions:

Contact teenage athletes with recurrent anterior shoulder instability can be treated with open Bankart repair with a low recurrence, excellent functional shoulder outcomes, and return to sport. A small amount of external rotation may be lost with this technique. Care must be taken when considering this method with throwing athletes (ie, quarterback or pitcher). The open Bankart should remain a viable alternative for the adolescent population with recurrent anterior instability.

Level of Evidence:

Level IV.
Investigating Relationships Between Health-Related Problems and Online Health Information Seeking
Authors: Oh Young Sam , Song Na Kyoung
Published: March 2016

Online health information seeking (OHIS) functions as a coping strategy to relieve health-related stress and problems. When people rate their health as poor or felt concern about their health, they frequently visit the Internet to seek health-related information in order to understand their symptoms and treatments. Regarding this role of OHIS, it is important to understand the relationships between health-related problems and OHIS. This study applies the Common-Sense Model as a theoretical lens to examine the relationship between health-related problems (ie, diagnosis of cancer, poor self-rated health, and psychological distress) and OHIS of adults in the US. Using the Health Information National Trends Survey 4 Cycle 1 (2012), a total of 2351 adult Internet users was included in this research. Hierarchical logistic regression analyses were conducted to examine the research model, and the model adding psychological distress resulted in a statistically significant improvement in model fit. In this study, lower levels of self-rated health and higher levels of psychological distress were significantly associated with higher odds of OHIS. Study findings support the idea that individuals' low levels of self-rated health and high levels of perceived psychological distress make people search for health-related information via the Internet in order to cope with health-related concern and distress.
The Utility of Diaton Tonometer Measurements in Patients With Ocular Hypertension, Glaucoma, and Glaucoma Tube Shunts: A Preliminary Study for its Potential Use in Keratoprosthesis Patients
Authors: Risma Justin M. , Tehrani Shandiz , Wang Kai , Fingert John H. , Alward Wallace L.M. , Kwon Young H.
Published: March 2016

Purpose:

Glaucoma is common in patients with the Boston type 1 keratoprosthesis (KPro). Because of the inability to perform corneal applanation in KPro patients, digital palpation is currently the mainstay for assessment of intraocular pressure (IOP). The purpose of this study was to determine whether the Diaton tonometer, which estimates IOP through transpalpebral scleral indentation, can reasonably detect high IOP when compared with Goldmann applanation tonometry (GAT) in patients with ocular hypertension, glaucoma, or glaucoma tube shunts. If reliable in these patients, it may be helpful in patients with KPros.

Materials and Methods:

We prospectively measured IOP using GAT and Diaton transpalpebral tonometry (DTT) on the upper and lower eyelids in 87 eyes of 57 adult participants with ocular hypertension and glaucoma, several of whom had glaucoma tube shunts.

Results:

The correlation coefficient between GAT and DTT on the upper eyelid was 0.64 (P<0.0001). For detecting an IOP of >21 mm Hg as measured by GAT, DTT on the upper eyelid had a sensitivity and specificity of 65% and 81%, respectively. The positive and negative predictive values were 74% and 73%, respectively. Bland-Altman analysis demonstrated limits of agreement of 2.0±19.5 mm Hg for GAT versus DTT on the upper eyelid. The presence of a tube shunt did not significantly affect the results.

Conclusions:

Diaton tonometry has a large margin of error compared with GAT in patients with ocular hypertension, glaucoma, and glaucoma tube shunts. However, given the current lack of an objective and quantitative method of IOP measurement in KPro patients, Diaton tonometry may be useful in this population as a supplement to digital palpation.
Identification of the Most Accurate Spectral-domain Optical Coherence Tomography Parameters in Eyes With Early High-Tension and Low-Tension Glaucoma
Authors: Gracitelli Carolina P.B. , Moreno Pilar A. , Leite Mauro T. , Prata Tiago S.
Published: March 2016

Purpose:

The aim of the study was to compare the diagnostic ability of macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) thickness in high-tension glaucoma (HTG) and low-tension glaucoma (LTG).

Patients and Methods:

Glaucoma was defined as glaucomatous optic neuropathy and reproducible visual field defects. Patients were classified as having LTG if untreated intraocular pressure was ≤21 mm Hg on 2 different occasions. Only eyes with early glaucoma (mean deviation <−6 dB) were included. All patients underwent spectral-domain optical coherence tomography (SDOCT) imaging.

Results:

A total of 56 normal subjects, 64 HTG patients, and 35 LTG patients were enrolled. Overall, after adjusting for mean deviation and age, the average pRNFL thickness in eyes with LTG was 18.7 µm thinner than in eyes with HTG (17% difference, P<0.01). In the HTG group, no significant difference was found between areas under the receiver operating characteristic curve (AUCs) for average GCC and average pRNFL thicknesses (0.77 vs. 0.68, P=0.06). In the LTG group, average pRNFL thickness had a significantly larger AUC compared with average GCC thickness (0.95 vs. 0.81, P<0.001). Comparing AUCs between HTG and LTG groups, although the average GCC had similar AUCs in both groups (P=0.47), the average pRNFL thickness had a significantly larger AUC in the LTG group (P<0.001).

Conclusions:

In eyes with early glaucoma, the pRNFL thickness scan seems to be a more accurate SDOCT protocol to identify those with LTG compared with the GCC thickness scan.
Evaluation of Retinal Nerve Fiber Layer Thickness and Ganglion Cell Complex Progression Rates in Healthy, Ocular Hypertensive, and Glaucoma Eyes With the Avanti RTVue-XR Optical Coherence Tomograph Based on 5-Year Follow-up
Authors: Holló Gábor , Zhou Qienyuan
Published: March 2016

Purpose:

To determine retinal nerve fiber layer thickness (RNFLT) and ganglion cell complex (GCC) progression rates for healthy eyes and undertreatment ocular hypertensive (OHT) and glaucoma eyes with the Avanti RTVue-XR optical coherence tomography.

Materials and Methods:

Seventeen healthy subjects (34 eyes), 17 medically treated OHT patients (34 eyes), and 67 medically treated glaucoma patients (122 eyes) were imaged prospectively at 6-month intervals (median follow-up 5.3 y, 11 visits).

Results:

A minimal negative correlation between baseline RNFLT and RNFLT progression was found in the glaucoma group (r=−0.1708, P=0.0493). In the other groups no correlation between baseline RNFLT or GCC and RNFLT or GCC progression was found, respectively. The mean±SD of the rate of change was −0.33±0.51, −0.44±0.62, and −0.69±0.93 μm/y for average RNFLT, and −0.53±0.36, −0.54±0.52, and −0.80±0.78 for average GCC, for the normal, OHT, and glaucoma eyes, respectively (P>0.05 for all between-group comparisons). In the normal group the highest progression rate was −1.52 μm/y for average RNFLT and −1.28 μm/y for average GCC. Despite maximal medical treatment, progression in the glaucoma group exceeded the highest progression rate of the normal group in 18 eyes (14.8%) for average RNFLT and 24 eyes (19.7%) for average GCC.

Conclusions:

We determined progression rates for untreated healthy and under treatment OHT and glaucoma eyes with the Avanti RTVue-XR optical coherence tomography. We found that an average RNFLT progression rate faster than −1.5 μm/y, and an average GCC progression rate faster than −1.3 μm/y are strongly suggestive for uncontrolled glaucomatous progression. Detection of uncontrolled structural progression with trend analysis may assist the early detection of fast progressors.
Contamination of urinary cultures in initial-stream versus later-stream urine in children undergoing bladder catheterization for the diagnosis of urinary tract infection
Authors: Megged Orli , Zilberstein Liron , Ben Shalom Efrat , Erlichman Matityahu
Published: March 2016

Background

Urine cultures obtained by bladder catheterization can be contaminated by bacteria colonizing the distal urethra. Data are inconclusive regarding the potential advantage of discarding the first few urine drops obtained by bladder catheterization and testing only the sample of late-stream urine, thus reducing the likelihood of urine culture contamination.

Aim

The aim of this study was to evaluate whether the incidence of contaminated urine cultures obtained by bladder catheterization can be reduced by splitting urine samples into ‘initial’ and ‘late’ samples and using only ‘late’ samples for culture.

Methods

Urine samples obtained by bladder catheterization from children younger than 2 years being evaluated for urinary tract infection were prospectively collected. Quantitative culture results were compared between initial-stream and late-stream urine samples.

Results

A total of 199 urine culture pairs of initial and late samples were compared. When using a cutoff value of at least 10 000 colony forming units/ml, late samples were superior to the initial ones in reducing contamination of urine cultures (P=0.029).

Conclusion

When obtaining urine cultures by bladder catheterization in children younger than 2 years, discarding the first few urine drops and using only the late stream for culture reduces false-positive culture results and improves the accuracy of urinary tract infection diagnosis.
Preventive Care Delivery to Young Children With Sickle Cell Disease
Authors: Bundy David G. , Muschelli John , Clemens Gwendolyn D. , Strouse John J. , Thompson Richard E. , Casella James F. , Miller Marlene R.
Published: March 2016

Preventive services can reduce the morbidity of sickle cell disease (SCD) in children but are delivered unreliably. We conducted a retrospective cohort study of children aged 2 to 5 years with SCD, evaluating each child for 14 months and expecting that he/she should receive ≥75% of days covered by antibiotic prophylaxis, ≥1 influenza immunization, and ≥1 transcranial Doppler ultrasound (TCD). We used logistic regression to quantify the relationship between ambulatory generalist and hematologist visits and preventive services delivery. Of 266 children meeting the inclusion criteria, 30% consistently filled prophylactic antibiotic prescriptions. Having ≥2 generalist, non-well child care visits or ≥2 hematologist visits was associated with more reliable antibiotic prophylaxis. Forty-one percent of children received ≥1 influenza immunizations. Children with ≥2 hematologist visits were most likely to be immunized (62% vs. 35% among children without a hematologist visit). Only 25% of children received ≥1 TCD. Children most likely to receive a TCD (42%) were those with ≥2 hematologist visits. One in 20 children received all 3 preventive services. Preventive services delivery to young children with SCD was inconsistent but associated with multiple visits to ambulatory providers. Better connecting children with SCD to hematologists and strengthening preventive care delivery by generalists are both essential.
Nursing Strategies to Increase Medication Safety in Inpatient Settings
Authors: Bravo Katherine , Cochran Gary , Barrett Ryan
Published: March 2016

Using data obtained through 2 multidisciplinary studies focused on medication safety effectiveness, this article provides nursing recommendations to decrease medication delivery errors. Strategies to minimize and address interruptions/distractions are proposed for the 3 most problematic time frames in which medication errors typically arise: medication acquisition, transportation, and bedside delivery. With planned interventions such as programmed scripts and hospital-based protocols to manage interruptions and distractions, patient safety can be maintained in the inpatient setting.
Emerging Role of Nestin as an Angiogenesis and Cancer Stem Cell Marker in Epithelial Ovarian Cancer: Immunohistochemical Study
Authors: Osman Wesam M. , Shash Lobna S. , Ahmed Naglaa S.
Published: March 2016

Ovarian cancer is the most fatal gynecologic malignancy and the existing second-line treatments have not been confirmed to be effective. Cancer stem cells research has a leading role to explore promising therapeutic applications. Nestin was postulated to reflect cancer stem cell properties in various tumors, correlating with poor prognosis. Furthermore, nestin is proposed as a reliable neovascularization marker. This study aimed to elucidate the status of nestin expression in various epithelial ovarian cancers (EOCs), its neoangiogenic properties, and investigate its potential association with clinicopathologic parameters. A total of 80 primary EOCs (37 serous, 20 Mucinous, 13 endometrioid, and 10 clear cell carcinomas) were immunohistochemically stained with nestin. Staining intensity and automated microvascular density (MVD) were assessed. Positive nestin expression was defined in ≈47.5% of all EOC; more commonly in ≈60% of the serous tumors. It was noticeably expressed in tumor spheroids. Nestin expression significantly correlated with overall tumor grade, lymph node, distant metastasis, and stage. Nestin+ neoangiogenesis was detectable in all cases (average=60.1). The nestin expression in tumor cells significantly correlated with Nestin+/MVD. The average Nestin+/MVD was significantly an independent predictor of high tumor stage. As a stem cell marker, nestin is expressed in cells of EOC including those growing as spherules and correlated with poor prognosis. Thus, nestin may be a novel therapeutic target for tumor angiogenesis and a combination therapy that includes nestin-targeting agents may be an effective therapeutic approach. In addition, detection of Nestin+/stem cells and Nestin+/MVD can be used as predictors of disease.
Pediatric Emergency Department Study of Cardiac Risk in the Novel Patient (PED SCReeN)
Authors: Horeczko Timothy , Park Jeanny K. , Mann Courtney , Milazzo Angelo
Published: March 2016

Objective

We compare pediatric cardiac risk classification and management recommendations between emergency physicians (EPs) and pediatric cardiologists (PCs) in children with a suspected new cardiac disorder.

Methods

We prospectively compared the work-up, assessment, classification, and disposition of patients aged 0 to 21 years presenting to the emergency department with a potential cardiac etiology in whom an electrocardiogram (ECG) was performed. The criterion standard was a blinded assessment by the PC-electrophysiologist after review of the history, physical examination, ancillary tests, and ECG.

Results

In 508 subjects, the median age was 15 years (interquartile range, 11–17 years), with a slight female predominance (281, 55.3%). The most common reasons for obtaining an ECG were: chest pain (158, 31.1%) and syncope, presyncope, or possible seizure (146, 28.7%). The most common auxiliary study was a chest radiograph (432, 85% of subjects). A total of 617 electrocardiographic diagnoses were made by EPs and 984 diagnoses by PCs. Sensitivities and specificities varied by discrete class, but disposition decisions were concordant (home or admission). The EPs were highly accurate for the need for emergent cardiology involvement (area under the curve, 0.89).

Conclusions

The EPs and PCs agreed on the evaluation and disposition of children at either low risk or high risk for an acute cardiac presentation in the emergency department. There was considerable variation in management recommendations in the intermediate risk children needing cardiology outpatient follow-up. We recommend the development and implementation of focused training modules on emergency pediatric cardiology and increased communication with pediatric cardiology to improve patient safety and resource utilization.
How Long Does it Take to Diagnose Appendicitis? Time Point Process Mapping in the Emergency Department
Authors: Abbas Paulette I. , Zamora Irving J. , Elder Simone C. , Brandt Mary L. , Lopez Monica E. , Orth Robert C. , Bisset George S. , Cruz Andrea T.
Published: March 2016

Objectives

Appendicitis is the most common surgical emergency encountered in the pediatric emergency department (ED). We analyzed the time course of children evaluated for suspected appendicitis in relation to implementation of a risk-stratified ultrasound scoring system and structured reporting template (Appy-Score).

Methods

In July 2013, a 6-level ultrasound (US)-based appendicitis scoring system was developed and implemented. The records of children (age ≤18 years) who underwent limited abdominal US exams for suspected appendicitis at a large academic pediatric ED were reviewed retrospectively. Time periods evaluated were from January 1 to April 1, 2013 (before implementation of the US scoring system, “PRE”) and July 1 to October 1, 2013 (after implementation of the US scoring system, “POST”). Times are presented as medians with interquartile range.

Results

A total of 926 children were included (median age, 9.5 years [range, 0.1–18 years]; 49% female). Four hundred eighty-one patients were evaluated PRE and 445 POST. When comparing the 2 groups, there were no differences in the PRE and POST periods with regard to time from US ordered to first read (102 vs 112 minutes, P = 0.30), US ordered to disposition (215 vs 208 minutes, P = 0.40) and operating room posting (121 vs 122 minutes, P = 0.59), and overall ED stay (329 vs 333 minutes, P = 0.39).

Conclusions

The development of a radiographic appendicitis score, although allowing for a standardized reporting method, did not significantly alter the ED process flow for evaluation of appendicitis. This reflects the complexities in ED throughput and reveals the need for additional factors to change to improve patient flow.
Temporal Changes of Texture Features Extracted From Pulmonary Nodules on Dynamic Contrast-Enhanced Chest Computed Tomography
Authors: Kim Hyungjin , Park Chang Min , Park Sang Joon , Song Yong Sub , Lee Jong Hyuk , Hwang Eui Jin , Goo Jin Mo
Published: March 2016

Objectives

The aim of this study was to describe the temporal changes of various texture features extracted from pulmonary nodules on dynamic contrast-enhanced computed tomography (DCE-CT) and to compare the feature values among multiple scanning time points. We also aimed to analyze the variability of texture features across multiple scan delay times.

Materials and Methods

This retrospective study was approved by the institutional review board of Seoul National University Hospital with waiver of patients' informed consent. Twenty patients (M:F, 6:14; mean age, 60.25 ± 11.97 years) with 20 lung nodules (mean size, 24.1 ± 12.3 mm) underwent DCE-CT with multiple scan delays (30, 60, 90, 120, 150, 180, 210, 240, 300, and 480 seconds) after precontrast scans. Lung nodule segmentation and texture feature extraction were performed at each time point using in-house software. Texture feature values were compared among the multiple time points using the Friedman test with post hoc pairwise Wilcoxon signed rank test. In addition, the dynamic range (DR) reflecting the variability between 2 time points to the interpatient range was calculated. Thereafter, we determined the stable time range that met both “DR greater than 0.90” and “no statistically significant difference” between all time point pairs for each feature. The degree of variability across all scan delay times was obtained using coefficients of variation.

Results

Standard deviation, variance, entropy, sphericity, discrete compactness, gray-level cooccurrence matrix (GLCM) inverse difference moment (IDM), GLCM contrast, and GLCM entropy did not show significant differences between scan delays of 30 and 180 seconds with DR greater than 0.90 between all time point pairs. When the range was narrowed down to 60 to 150 seconds, an additional 2 values (mean and homogeneity) showed stability. Among the 13 texture features, entropy, sphericity, discrete compactness, and GLCM entropy exhibited the lowest variability (coefficient of variation ≤5%).

Conclusions

Most texture features exhibited stability with low variation between 60 and 150 seconds on DCE-CT. Thus, texture features extracted from contrast-enhanced CT with a scan delay range of 60 to 150 seconds can be used for tumor characterization despite the heterogeneity in delay time.
The Effects of Ribosome Autocatalysis and Negative Feedback in Resource Competition
Authors: Chandra Fiona A , Del Vecchio Domitilla
Published: March 2016

Background

Resource competition, and primarily competition for ribosomes, can lead to unexpected behavior of genetic circuits and has recently gained renewed attention with both experimental and theoretical studies. Current models studying the effects of resource competition assume a constant production of ribosomes and these models describe the experimental results well. However, ribosomes are also autocatalytic since they are partially made of protein and autocatalysis has been shown to have detrimental effects on a system’s stability and robustness. Additionally, there are known feedback regulations on ribosome synthesis such as inhibition of rRNA synthesis via ppGpp.

Results

Here, we develop two-state models of ribosome and protein synthesis incorporating autocatalysis and feedback to investigate conditions under which these regulatory actions have a significant effect in situations of increased ribosome demand. Our modeling results indicate that for sufficiently low demand, defined by the mRNA level of synthetic genes, autocatalysis has little or no effect. However, beyond a certain demand level, the system goes through a transcritical bifurcation at which the only non-negative steady state is at zero ribosome concentration. The presence of negative feedback, in turn, can shift this point to higher demand values, thus restoring the qualitative behavior observed in a model with a constant ribosome production at low demand. However, autocatalysis affects the dynamics of the system and can lead to an overshoot in the temporal response of the synthetic genes to changes in induction level.

Conclusion

Our results show that ribosome autocatalysis has a significant effect on the system robustness to increases in ribosome demand, however the existing negative feedback on ribosome production compensates for the effects of the necessary autocatalytic loop and restores the behavior seen in the system with constant ribosome production. These findings explain why previous models with constant ribosome production reproduce the steady state behavior well, however incorporating autocatalysis and feedback is needed to capture the transient behavior.
The Ensembl Variant Effect Predictor
Authors: McLaren William , Gil Laurent , Hunt Sarah E , Riat Harpreet Singh , Ritchie Graham R. S. , Thormann Anja , Flicek Paul , Cunningham Fiona
Published: March 2016

The Ensembl Variant Effect Predictor (VEP) is a powerful toolset for the analysis, annotation and prioritization of genomic variants, including in non-coding regions.

The VEP accurately predicts the effects of sequence variants on transcripts, protein products, regulatory regions and binding motifs by leveraging the high quality, broad scope, and integrated nature of the Ensembl databases. In addition, it enables comparison with a large collection of existing publicly available variation data within Ensembl to provide insights into population and ancestral genetics, phenotypes and disease.

The VEP is open source and free to use. It is available via a simple web interface (http://www.ensembl.org/vep), a powerful downloadable package, and both Ensembl’s Perl and REST application program interface (API) services.
Preprint: A robust peptidomics mass spectrometry platform for measuring oxytocin in plasma and serum
Authors: Brandtzaeg Ole Kristian , Johnsen Elin , Roberg-Larsen Hanne , Seip Knut Fredrik , Leknes Siri , Lundanes Elsa , Wilson Steven Ray
Published: March 2016

Current approaches to measuring the cyclic peptide oxytocin in plasma/serum are associated with poor selectivity and/or inadequate sensitivity. We here describe a high performance nano liquid chromatography-mass spectrometry platform for measuring OT in human plasma/serum. The platform is extremely robust, allowing laborious sample clean-up steps to be omitted. OT binds strongly to plasma proteins, but a reduction/alkylation procedure breaks this bond, allowing ample detection of total OT. The method showed excellent quantitation properties, and was used to determine total OT levels to 0.5-1.2 ng/mL (evaluated with human plasma and cord serum). The method is compatible with accessible mass spectrometry instrumentation, finally allowing selective and easily comparable oxytocin measurements.
A Novel Initiation Pathway inEscherichia ColiTranscription
Authors: Lerner Eitan , Chung SangYoon , Allen Benjamin L. , Wang Shuang , Lee Jookyung J. , Lu Winson S. , Grimaud Wilson L. , Ingargiola Antonino , Michalet Xavier , Alhadid Yazan , Borukhov Sergei , Strick Terence , Taatjes Dylan J. , Weiss Shimon
Published: March 2016

Initiation is a highly regulated, rate-limiting step in transcription. We employed a series of approaches to examine the kinetics of RNA polymerase (RNAP) transcription initiation in greater detail. Quenched kinetics assays, in combination with magnetic tweezer experiments and other methods, showed that, contrary to expectations, RNAP exit kinetics from later stages of initiation (e.g. from a 7-base transcript) was markedly slower than from earlier stages. Further examination implicated a previously unidentified intermediate in which RNAP adopted a long-lived backtracked state during initiation. In agreement, the RNAP-GreA endonuclease accelerated transcription kinetics from otherwise delayed initiation states and prevented RNAP backtracking. Our results indicate a previously uncharacterized RNAP initiation state that could be exploited for therapeutic purposes and may reflect a conserved intermediate among paused, initiating eukaryotic enzymes.

Significance:

Transcription initiation by RNAP is rate limiting owing to many factors, including a newly discovered slow initiation pathway characterized by RNA backtracking and pausing. This backtracked and paused state occurs when all NTPs are present in equal amounts, but becomes more prevalent with NTP shortage, which mimics cellular stress conditions. Pausing and backtracking in initiation may play an important role in transcriptional regulation, and similar backtracked states may contribute to pausing among eukaryotic RNA polymerase II enzymes.
Global transcriptional response of Dickeya dadantii to environmental stimuli relevant to the plant infection
Authors: Jiang Xuejiao , Zghidi‐Abouzid Ouafa , Oger‐Desfeux Christine , Hommais Florence , Greliche Nicolas , Muskhelishvili Georgi , Nasser William , Reverchon Sylvie
Published: March 2016

Dickeya species are soft rot disease‐causing bacterial plant pathogens and an emerging agricultural threat in Europe. Environmental modulation of gene expression is critical for Dickeya dadantii pathogenesis. While the bacterium uses various environmental cues to distinguish between its habitats, an intricate transcriptional control system coordinating the expression of virulence genes ensures efficient infection. Understanding of this behaviour requires a detailed knowledge of expression patterns under a wide range of environmental conditions, which is currently lacking. To obtain a comprehensive picture of this adaptive response, we devised a strategy to examine the D. dadantii transcriptome in a series of 32 infection‐relevant conditions encountered in the hosts. We propose a temporal map of the bacterial response to various stress conditions and show that D. dadantii elicits complex genetic behaviour combining common stress‐response genes with distinct sets of genes specifically induced under each particular stress. Comparison of our dataset with an in planta expression profile reveals the combined impact of stress factors and enables us to predict the major stress confronting D. dadantii at a particular stage of infection. We provide a comprehensive catalog of D. dadantii genomic responses to environmentally relevant stimuli, thus facilitating future studies of this important plant pathogen.
Age, introduction of solid feed and weaning are more important determinants of gut bacterial succession in piglets than breed and nursing mother as revealed by a reciprocal cross‐fostering model
Authors: Bian Gaorui , Ma Shouqing , Zhu Zhigang , Su Yong , Zoetendal Erwin G. , Mackie Roderick , Liu Junhua , Mu Chunlong , Huang Ruihua , Smidt Hauke , Zhu Weiyun
Published: March 2016

A reciprocal cross‐fostering model with an obese typical Chinese piglet breed and a lean Western breed was used to identify genetic and maternal effects on the acquisition and development gut bacteria from birth until after weaning. Pyrosequencing of 16S rRNA genes results revealed an age‐ and diet‐dependent bacterial succession process in piglets. During the first 3 days after birth, the bacterial community was relatively simple and dominated by Firmicutes with 79% and 65% relative abundance for Meishan and Yorkshire piglets, respectively. During the suckling period until day 14, the piglet breed and the nursing mother lead to increasing differentiation of the fecal bacterial community, with specific bacteria taxa associated with breed, and others with the nursing sow most likely due to its milk composition. Although the effect of nursing mother and the breed were evident through the suckling period, the introduction of solid feed and subsequent weaning were the major events occurring that dominated succession of the gut microbiota in the early life of piglets. This piglet cross‐fostering model is a useful tool for studying the effects of diet, host genetics and the environment on the development and acquisition of the gut microbiota and over longer studies the subsequent impact on growth, health and performance of pigs.
TRI6 and TRI10 play different roles in the regulation of deoxynivalenol (DON) production by cAMP signalling in Fusarium graminearum
Authors: Jiang Cong , Zhang Chengkang , Wu Chunlan , Sun Panpan , Hou Rui , Liu Huiquan , Wang Chenfang , Xu Jin‐Rong
Published: March 2016

The biosynthesis of mycotoxin deoxynivalenol (DON) in Fusarium graminearum is regulated by two pathway‐specific transcription factors Tri6 and Tri10 and affected by various host and environmental factors. In this study, we showed that cyclic adenosine monophosphate (cAMP) treatment induced DON production by stimulating TRI gene expression and DON‐associated cellular differentiation in F. graminearum. Interestingly, exogenous cAMP had no effects on the tri6 mutant but partially recovered the defect of tri10 mutant in DON biosynthesis. Although the two cAMP phosphodiesterase genes PDE1 and PDE2 had overlapping functions in vegetative growth, conidiation, sexual reproduction and plant infection, deletion of PDE2 but not PDE1 activated intracellular PKA activities and increased DON production. Whereas the tri6 pde2 mutant failed to produce DON, the tri10 pde2 double mutant produced a significantly higher level of DON than the tri10 mutant. Cellular differentiation associated with DON production was stimulated by exogenous cAMP or deletion of PDE2 in both tri10 and tri6 mutants. These data indicate that TRI6 is essential for the regulation of DON biosynthesis by cAMP signalling but elevated PKA activities could partially bypass the requirement of TRI10 for TRI gene‐expression and DON production, and Pde2 is the major cAMP phosphodiesterase to negatively regulate DON biosynthesis in F. graminearum.
Exchange of core chromosomes and horizontal transfer of lineage‐specific chromosomes in Fusarium oxysporum
Authors: Vlaardingerbroek Ido , Beerens Bas , Rose Laura , Fokkens Like , Cornelissen Ben J. C. , Rep Martijn
Published: March 2016

Horizontal transfer of supernumerary or lineage‐specific (LS) chromosomes has been described in a number of plant pathogenic filamentous fungi. So far it was not known whether transfer is restricted to chromosomes of certain size or properties, or whether ‘core’ chromosomes can also undergo horizontal transfer. We combined a directed and a non‐biased approach to determine whether such restrictions exist. Selection genes were integrated into the genome of a strain of Fusarium oxysporum pathogenic on tomato, either targeted to specific chromosomes by homologous recombination or integrated randomly into the genome. By testing these strains for transfer of the marker to another strain we could confirm transfer of a previously described mobile pathogenicity chromosome. Surprisingly, we also identified strains in which (parts of) core chromosomes were transferred. Whole genome sequencing revealed that this was accompanied by the loss of the homologous region from the recipient strain. Remarkably, transfer of the mobile pathogenicity chromosome always accompanied this exchange of core chromosomes.
On the Existence of a Middle‐Income Trap
Authors: Ye Longfeng , Robertson Peter E.
Published: March 2016

The concept of a ‘middle‐income trap’ has attracted enormous interest, but the existing literature lacks formal tests. We develop and apply a test of some necessary conditions for a country to be in a middle‐income trap that take into account short‐run dynamics, stochastic trends and structural breaks. We find that only seven countries satisfy our definition of a middle income trap.