bluuebunny/crossref_metadata_2025 huggingface dataset:
Incremental Value of Pocket‐Sized Echocardiography in Addition to Physical Examination during Inpatient Cardiology Evaluation: A Multicenter Italian Study (SIEC)
Authors: Di Bello Vitantonio , La Carrubba Salvatore , Conte Lorenzo , Fabiani Iacopo , Posteraro Alfredo , Antonini‐Canterin Francesco , Barletta Valentina , Nicastro Irene , Mariotti Egidio , Severino Sergio , Caso Pio , Benedetto Frank , Savino Ketty , Carerj Scipione ,   SIEC (Italian Society of Cardiovascular Echography)
Published: April 2015

Background

We prospectively assessed the incremental value of a pocket‐sized echocardiography (PSE) device during cardiology consultations, in addition to physical examination, ECG reading, and chest x‐ray.

Methods

A total of 443 consecutive patients (53% men), referred for bedside consultations, underwent physical examination, ECG, and CXR, followed by PSE examination. The physician completed a detailed questionnaire (clinical and echocardiographic data, scanning time, abnormal results). Receiver operating characteristic (ROC) curve analysis was generated to test the predictive discrimination value of the different methods. The incremental value of PSE examination compared to clinical visit alone or combined with ECG results was expressed as a global chi‐square value.

Results

The PSE examination did not influence the definitive diagnosis in only 23.5% of cases, while 25.3% of the diagnoses were confirmed and verified by PSE. The clinical diagnosis was enriched by PSE in 21.9% of cases, and the diagnosis was changed in 26.2%. The area under curve (AUC) of physical examination + ECG results (sensitivity: 80%; specificity: 67%) was significantly higher than physical examination alone (sensitivity: 75%; specificity: 62%) (P < 0.0002), and the AUC of PSE results (sensitivity: 88%; specificity: 86%) was significantly higher than physical examination + ECG results (P < 0.0001). The PSE results, combined with clinical and ECG results, had a significant incremental diagnostic value during cardiology consultation when compared to the clinical visit alone or with ECG results (P < 0.0001).

Conclusions

PSE had an incremental diagnostic value during bedside cardiology consultation, increasing the number of appropriate diagnoses and reducing the routine use of echocardiography.
Patients characteristics influencing the longitudinal utilization of steroids in multiple sclerosis – an observational study
Authors: Rommer Paulus S. , Buckow Karoline , Ellenberger David , Friede Tim , Pitschnau‐Michel Dorothea , Fuge Jan , Stüve Olaf , Zettl Uwe K. ,   the German Multiple Sclerosis (MS) Registry of the German National MS Society (DMSG)
Published: April 2015

Background

Multiple Sclerosis is the most common disease in young adults affecting the central nervous system. Disease may progress with acute attacks (relapsing MS) or continuously (progressive MS). Glucocorticosteroids are used in the treatment of acute attacks. The aim of this study was to analyse characteristics of patients with MS, and their influence on current treatment patterns of relapses with glucocorticosteroids.

Design

In 2001, the German National MS Society initiated the German MS‐Registry. Patients with relapsing MS were included (n = 5106) from this registry. Logistic regression models were used to detect trends over time. The likelihood of administration of steroids is modelled in dependence of calendar year and in dependence to confounders in treatment conditions. The sample size allows that odds ratios can be detected with a power of 90% (alpha = 0·05).

Results

Administration of glucocorticosteroids was influenced by EDSS (P < 0·0001), age (P < 0·0001) and disease duration (P < 0·0001). Therapy administration in an outpatient setting was more likely in patients with higher EDSS (P < 0·0001) and longer disease duration (P < 0·0001). The utilization of glucocorticosteroids increased with higher EDSS for all relapsing patients. Interestingly, all overutilization of glucocorticosteroids decreased over time and was accompanied by a steadily increased administration of emergent therapeutics. Although there are about 70% of registered patients with relapsing MS on immune‐modulatory treatment, almost 60% of them received glucocorticosteroids for treatment of relapses.

Conclusions

Treatment patterns with glucocorticosteroids in patients with MS are influenced mainly by EDSS and disease duration. The decline in the utilization of glucocorticosteroids is accompanied by an increase in natalizumab treatment.
Effects of water clarity and other environmental factors on trophic niches of two sympatric piscivores
Authors: Stasko Ashley D. , Johnston Tom A. , Gunn John M.
Published: April 2015

Water clarity can have a profound influence on aquatic ecosystem structure and processes via its effects on physical habitat (e.g., thermal regime, macrophyte density) and behavioural responses of biota (e.g., predator avoidance, reaction distances, foraging efficiency). Changes in foraging efficiencies under varying water clarity conditions are well documented for many freshwater piscivores in laboratory studies, but the influence of visual foraging conditions on interspecific trophic dynamics is poorly understood in wild populations, especially within water clarity ranges that are realistic for north‐temperate boreal lakes.

Here, we used stable isotopes of nitrogen (15N/14N) and carbon (13C/12C) in fish muscle tissue to investigate how resource partitioning between two sympatric visual piscivores is related to water clarity and other habitat variables in 28 small (100–200 ha) Boreal Shield lakes. One of the species is adapted for foraging in low subsurface illumination (walleye, Sander vitreus) and the other in high subsurface illumination (smallmouth bass, Micropterus dolomieu).

Trophic niche dimensions of the dark‐adapted predator did not respond significantly to differences in water clarity. In contrast, total isotopic niche space of the light‐adapted predator decreased significantly with increasing water clarity through greater use of pelagic resources and a narrower range of trophic levels, although these relationships were weak.

Niche overlap ranged from 0 to 65%, but was not significantly related to water clarity. Rather, indices of prey availability appeared to be much stronger predictors of trophic interactions. Both species occupied more similar food‐web positions when yellow perch (Perca flavescens) abundance was higher, and had more similar niche size and trophic evenness with decreasing prey fish species richness.

Results indicate that the trophic ecology of predators adapted to foraging in low light conditions is less influenced by water clarity than that of predators adapted to foraging in high light conditions. However, prey availability, rather than the environmental conditions in which foraging occurs, may be a more important driver of resource partitioning among generalists even when light conditions favour one species’ foraging strategy over another.
It's complicated – Factors predicting decisional conflict in prenatal diagnostic testing
Authors: Muller Cécile , Cameron Linda D.
Published: April 2015

Background

The technologies currently available to detect the presence of foetal genetic abnormalities are complex, and undergoing prenatal diagnostic testing can have wide‐ranging repercussions. Before individuals can decide with certainty whether or not to take these tests, they first need to grasp the many psychosocial and clinical dimensions of prenatal genetic testing.

Objective

To test a model integrating key psychosocial and clinical factors as predictors of decisional conflict in decisions about whether or not to undergo prenatal genetic testing.

Method

Adults (n = 457) read one of four hypothetical scenarios asking them to imagine expecting a child and considering the option of a prenatal test able to detect a genetic condition; age of condition onset (birth vs. adulthood) and its curability (no cure vs. curable) were manipulated. Participants completed measures of decisional conflict, perceived benefits from normal results, test response efficacy, condition coherence, child‐related worry, perceived disagreement with the other parent's preference, motivation to comply with doctors' perceived preferences, and parity.

Results

Prenatal testing decisional conflict was positively predicted by perceiving normal results as beneficial, doubting the test's reliability, lacking understanding of the genetic condition, worrying about the health of the foetus, perceiving differences of opinion from partner/spouse, wanting to follow doctors' preferences, and being childless.

Discussion

These results, of growing relevance given the increasing availability of new technologies in pregnancy care, can inform communication strategies that facilitate coupless' decision making.

Conclusion

This study provides insights into factors that might complicate prenatal testing decision making.
Exploring teachers' ontologies of English: Monolithic conceptions of grammar in a group of Chinese teachers
Authors: Hall Christopher J , Wicaksono Rachel , Liu Shu , Qian Yuan , Xu Xiaoqing
Published: April 2015

This study presents a conceptual framework for exploring teachers' ontologies of English and investigates how a group of Chinese university teachers of English conceive of, and orient to, the language. Interview data suggest that participants orient to both a monolithic view as well as the ‘plurilithic’ reality. The data reveal that monolithic ontologies are associated primarily with classroom contexts, whereas plurilithic ontologies are activated when usage is in focus. Particularly significant is teachers' monolithic conception of grammar, compared to plurilithic conceptions of lexis and pronunciation. We propose that usage‐based approaches to grammar might offer teachers a way to reconcile their apparently contradictory ontologies and help them challenge the deficit view of learning inherent in the monolithic approach.
Morphological MRI Characteristics of Recent Small Subcortical Infarcts
Authors: Gattringer Thomas , Eppinger Sebastian , Pinter Daniela , Pirpamer Lukas , Berghold Andrea , Wünsch Gerit , Ropele Stefan , Wardlaw Joanna M. , Enzinger Christian , Fazekas Franz
Published: April 2015

Background

New imaging criteria for recent small subcortical infarcts have recently been proposed, replacing the earlier term ‘lacunar infarction’, but their applicability and impact on lesion selection is yet unknown.

Aims

To collect information on the morphologic characteristics and variability of recent small subcortical infarcts on magnetic resonance imaging in regard to lesion location and demographic variables.

Methods

We identified all patients with acute stroke and cerebral magnetic resonance imaging from 2008 to 2013 in our hospital database and selected those with a single recent small subcortical infarct defined by an estimated maximal axial diameter of 20 mm. Recent small subcortical infarcts were segmented on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence to calculate the largest axial and longitudinal diameter and lesion volume. We assessed morphometric differences of recent small subcortical infarcts regarding location and demographic variables and the impact of different recent small subcortical infarct definitions on lesion selection.

Results

Three hundred forty-four patients (median age 72; range 25–92 years, 65% male) were selected. Most recent small subcortical infarcts were located in the basal ganglia ( n = 111), followed by pons ( n = 92), thalamus ( n = 77), and centrum semiovale ( n = 64). Quantitative measurements confirmed visual assessment of the axial diameter in 95%. All morphometric variables were strongly intercorrelated and comparable on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence. Recent small subcortical infarcts in the basal ganglia were significantly larger both in the axial and longitudinal direction compared with other regions. Dichotomization of recent small subcortical infarcts according to axial (≤ / >15 mm) or longitudinal (≤ / >20 mm) sizes resulted in different regional frequencies and distributions. Age, gender, and time from stroke onset to magnetic resonance imaging did not influence lesion metrics or the distribution of recent small subcortical infarcts.

Conclusions

Our study confirms the recent neuroimaging criteria for recent small subcortical infarcts as a practical concept. Definitions of the maximal axial and longitudinal diameter have a significant impact on the frequency and distribution of selected infarcts, which has to be considered for future studies.
Reflection as a facilitator of teachers' innovative work behaviour
Authors: Messmann Gerhard , Mulder Regina H.
Published: April 2015

The aim of this study was to investigate the role of reflection as a preparatory mechanism for employees' engagement in innovative work behaviour (IWB). This issue was explored in a study with 67 teachers at the highest level of German secondary education. Specifically, we investigated whether teachers who reflected on work tasks, the social context and their work performance were more engaged in the exploration of opportunities for innovation as well as the generation, promotion and realization of innovative ideas. By applying path modelling, we found that work‐related reflection facilitated all dimensions of IWB. Teachers' IWB most strongly depended on their performance‐related reflection. Also, reflecting on work tasks and the social context affected teachers' IWB indirectly by benefitting their performance‐related reflection. As a consequence, reflection should be valued as a resource for innovation and professional development as well as a vital component of work routines, organizational cultures and job training.
Lower Blood Pressure and Gray Matter Integrity Loss in Older Persons
Authors: Foster‐Dingley Jessica C. , Moonen Justine E.F. , van den Berg‐Huijsmans Anne A. , de Craen Anton J.M. , de Ruijter Wouter , van der Grond Jeroen , van der Mast Roos C.
Published: April 2015

In contrast to middle age, it is unclear whether blood pressure (BP) in older persons is associated with cerebral small vessel disease (cSVD). The authors evaluated the association of BP with signs of cSVD as well as gray and white matter integrity in older persons. In 220 participants aged 75 years and older from the Discontinuation of Antihypertensive Treatment in the Elderly (DANTE) study, cSVD was assessed with conventional magnetic resonance imaging, and microstructural integrity with diffusion tensor and magnetization transfer (MT) imaging. BP measures were not associated with cSVD. However, lower systolic and diastolic BP and mean arterial pressure were associated with decreased gray matter MT ratio peak height and MT ratio in cortical gray matter. Mean arterial pressure was also associated with increased gray matter diffusivity. A lower level of BP was especially associated with worse gray matter integrity. Results suggest that not only upper but preferably lower thresholds of BP values should be observed in older persons.
The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue
Authors: Egom Emmanuel E. , Kruzliak Peter , Rotrekl Vladimir , Lei Ming
Published: April 2015

The sphingosine‐1‐phosphate (S1P) receptor modulator, fingolimod (FTY720), has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular (AV) conduction block have been reported in some patients after the first dose. The underlying mechanism of this AV node conduction blockade is still not well‐understood. In this study, we hypothesize that expression of this particular arrhythmia might be related to a direct effect of FTY720 on AV node rather than a parasympathetic mimetic action. We, therefore, investigated the effect of FTY720 on AV nodal, using in vitro rat model preparation, under both basal as well as ischaemia/reperfusion conditions. We first look at the expression pattern of S1P receptors on the AV node using real‐time PCR. Although all three S1P receptor isoforms were expressed in AVN tissues, S1P1 receptor isoform expression level was higher than S1P2 and S1P3. The effect of 25 nM FTY720 on cycle length (CL) was subsequently studied via extracellular potentials recordings. FTY720 caused a mild to moderate prolongation in CL by an average 9% in AVN (n = 10, P < 0.05) preparations. We also show that FTY720 attenuated both ischaemia and reperfusion induced AVN rhythmic disturbance. To our knowledge, these remarkable findings have not been previously reported in the literature, and stress the importance for extensive monitoring period in certain cases, especially in patients taking concurrently AV node blocker agents.
Cost‐effectiveness of non‐surgical peri‐implantitis treatments
Authors: Listl Stefan , Frühauf Nadine , Dannewitz Bettina , Weis Christiane , Tu Yu‐Kang , Chang Huei‐Ju , Faggion Clovis M.
Published: April 2015

Aim

The purpose of the present study was to assess the cost‐effectiveness of various alternatives of non‐surgical peri‐implantitis treatment.

Materials and Methods

A decision analytical model was constructed and populated with parameter estimates from recent literature for reduction in pocket probing depth (PPD) in response to eight different treatment alternatives. A micro‐costing approach combined with an online expert survey was applied to simulate a decision‐making scenario taking place in Germany. The treatment alternatives providing the most advantageous cost/outcome combinations were identified according to the net benefit criterion. Uncertainties regarding model input parameters were incorporated via simple and probabilistic sensitivity analysis based on Monte Carlo simulation.

Results

In the base case scenario, debridement alone, Air‐Flow®, debridement combined with PerioChip®, and debridement combined with local antibiotics were identified as treatment strategies with comparably better value for money than Er:YAGlaser monotherapy, Vector™System, debridement combined withCHX, and photodynamic therapy. Sensitivity analysis revealed considerable decision uncertainty corresponding to limited evidence about different treatment alternatives for peri‐implantitis treatment.

Conclusions

Derivation of robust treatment recommendations for peri‐implantitis requires more comprehensive and patient‐centred evidence on peri‐implantitis treatments.
Effects of non‐equilibrium plasma in the treatment of ligature‐induced peri‐implantitis
Authors: Shi Qi , Song Ke , Zhou Xincai , Xiong Zilan , Du Tianfeng , Lu Xinpei , Cao Yingguang
Published: April 2015

Aim

To evaluate the effects of non‐equilibrium plasma in the treatment of ligature‐induced peri‐implantitis in beagle dogs.

Materials and Methods

Six beagles received 12 implants installed in the position of the fourth mandibular premolars. Ligature‐induced peri‐implantitis was initiated at 3 months post‐implantation. When approximately 40% of the supporting bone was lost, the ligatures were removed. The implants were subjected to the muco‐periosteal scaling and chlorhexidine irrigation with or without plasma irrigation. Three months later, clinical, radiographic and microbiological analyses were performed. Block biopsies were prepared for micro‐CT and histomorphometric analysis. The primary outcome was the difference in bone healing of peri‐implant sites, and the secondary outcomes included changes in clinical parameters (SBI, PD) and bacterial detection.

Results

At baseline, no significant differences were observed between the two groups. At 3 months post‐treatment, the plasma group showed a significantly higher bone level than the control group (p < 0.05), a significantly decreased detection of bacteria (Porphyromonas gingivalis and Tannerella forsythia) (p < 0.05), and a significant improvement in clinical examination (p < 0.05).

Conclusions

Within the limits of this study, non‐equilibrium plasma treatment as an adjunct to the conventional therapy is a feasible approach for the treatment of peri‐implantitis.
Developmental differences in intra‐individual variability in children with ADHD and ASD
Authors: van Belle Janna , van Hulst Branko M. , Durston Sarah
Published: April 2015

Background

Intra‐individual variability reflects temporal variation within an individual's performance on a cognitive task. Children with developmental disorders, such as ADHD and ASD show increased levels of intra‐individual variability. In typical development, intra‐individual variability decreases sharply between the ages 6 and 20. The tight link between intra‐individual variability and age has led to the suggestion that it may be marker of neural development. As there is accumulating evidence that ADHD and ASD are characterised by atypical neurodevelopmental trajectories, we set out to explore developmental changes in intra‐individual variability in subjects with ADHD and ASD.

Method

We used propensity score matching to match a cross‐sectional sample of children with ADHD, ASD and control subjects (N = 405, aged 6–19 years old) for age, IQ and gender. We used ex‐Gaussian distribution parameters to characterise intra‐individual variability on fast responses (sigma) and slow responses (tau).

Result

Results showed that there was a similar decrease in mean response times with age across groups, and an interaction between age and group for measures of variability, where there was a much lower rate of change in the variability parameters (sigma and tau) for subjects with ASD compared with the other two groups. Subjects with ADHD had higher intra‐individual variability, reflected by both sigma and tau, but the rate of decrease in variability with age was similar to that of the controls.

Conclusion

These results suggest that subjects with ADHD, ASD and controls differ in the rate at which intra‐individual variability decreases during development, and support the idea that intra‐individual variability may be a marker of neural development, mimicking the neurodevelopmental changes in these disorders.
The validity, reliability and acceptability of the SAVASI; a new self‐assessment score in vitiligo
Authors: Komen L. , van der Kraaij G.E. , van der Veen J.P.W. , de Rie M.A. , Wolkerstorfer A.
Published: April 2015

Background

Vitiligo is a common depigmenting skin disorder that can influence a patient's quality of life. Although patient‐orientated medicine is an emerging concept, a self‐assessment tool to assess the degree of depigmentation in vitiligo is not yet available. Therefore, we developed the SAVASI, a self‐assessment tool that uses the same basic principles as the VASI.

Objective

To assess the validity, reliability and acceptability of the SAVASI.

Methods

To assess the validity of the SAVASI, we compared the scores assessed by the patient with the scores of the VASI assessed by the physician. To assess the intra‐rater reliability, the correlation between the baseline SAVASI and the SAVASI after 2 weeks was calculated. To assess the acceptability, patients indicated the time needed to complete the SAVASI and the patient assessed the difficulty of the questionnaire on a five‐point scale. The Skindex‐29 was used to determine the quality of life. The overestimation of the SAVASI compared to the VASI was calculated by subtracting the VASI scores off from the SAVASI scores.

Results

A high correlation between the VASI and the SAVASI (ICC 0.97, 95% CI: 0.95–0.98) was found in 60 patients. The intra‐rater reliability of the SAVASI (ICC 0.75, 95% CI 0.54–0.87) was adequate in 31 patients. Fifty (83%) of the patients completed the questionnaire within 10 min and only five (8%) of the patients considered the SAVASI hard. We found no correlation between overestimation of the SAVASI score and the Skindex‐29 score.

Conclusion

The SAVASI is a valid, reliable and acceptable self‐assessment tool to measure the degree of depigmentation in vitiligo. With the SAVASI the degree of depigmentation can reliably be assessed by the patient themselves which can be useful in large (epidemiological) studies. Furthermore, this could contribute to the patient's disease insight and therapy loyalty.
Protein pheromone expression levels predict and respond to the formation of social dominance networks
Authors: Nelson A. C. , Cunningham C. B. , Ruff J. S. , Potts W. K.
Published: April 2015

Communication signals are key regulators of social networks and are thought to be under selective pressure to honestly reflect social status, including dominance status. The odours of dominants and nondominants differentially influence behaviour, and identification of the specific pheromones associated with, and predictive of, dominance status is essential for understanding the mechanisms of network formation and maintenance. In mice, major urinary proteins (MUPs) are excreted in extraordinary large quantities and expression level has been hypothesized to provide an honest signal of dominance status. Here, we evaluate whether MUPs are associated with dominance in wild‐derived mice by analysing expression levels before, during and after competition for reproductive resources over 3 days. During competition, dominant males have 24% greater urinary MUP expression than nondominants. The MUP darcin, a pheromone that stimulates female attraction, is predictive of dominance status: dominant males have higher darcin expression before competition. Dominants also have a higher ratio of darcin to other MUPs before and during competition. These differences appear transient, because there are no differences in MUPs or darcin after competition. We also find MUP expression is affected by sire dominance status: socially naive sons of dominant males have lower MUP expression, but this apparent repression is released during competition. A requisite condition for the evolution of communication signals is honesty, and we provide novel insight into pheromones and social networks by showing that MUP and darcin expression is a reliable signal of dominance status, a primary determinant of male fitness in many species.
Prospective population‐based cohort of inflammatory bowel disease in the biologics era: Disease course and predictors of severity
Authors: Niewiadomski Olga , Studd Corrie , Hair Chris , Wilson Jarrad , Ding Nik S , Heerasing Neel , Ting Alvin , McNeill John , Knight Ross , Santamaria John , Prewett Emily , Dabkowski Paul , Dowling Damian , Alexander Sina , Allen Ben , Popp Benjamin , Connell William , Desmond Paul , Bell Sally
Published: April 2015

Background and Aim

We have previously found high incidence of inflammatory bowel disease (IBD) in Australia. A population‐based registry was established to assess disease severity, frequency of complications, and prognostic factors.

Methods

Incident cases were prospectively identified over 4 years. Early disease severity was assessed according to need for hospitalization and resective surgery and medication use.

Results

We report on the early outcomes (median 18 months, range 12–60 months) for 252 patients comprising 146 with Crohn's disease (CD), 96 with ulcerative colitis (UC), and 10 IBD undifferentiated. Eighty‐seven percent of CD patients had inflammatory disease at diagnosis, and this reduced to 73% at 5 years (n = 38). Immunomodulators were prescribed in 57% of CD patients and 19% with UC. A third of all CD patients were hospitalized, the majority (77%) in the first 12 months. Risk factors for hospitalization included penetrating, perianal, and ileocolonic disease (P < 0.05). Twenty‐four percent of UC patients were hospitalized, most within the first 12 months. Intestinal resection rates were 13% at 1 year in CD and 26% at 5 years. Risk factors include penetrating and stricturing disease (P < 0.001) and ileal involvement (P < 0.05). Colectomy rates in UC were 2% and 13% at 1 and 5 years. High C‐reactive protein (CRP) at diagnosis was associated with colectomy.

Conclusions

A high rate of inflammatory disease, frequent immunomodulator use in CD, and a low rate of surgery in both CD and UC were identified. In CD, ileal involvement and complex disease behavior are associated with a more severe disease course, while in UC a high CRP predicted this outcome.
Pretest prediction and diagnosis of metastatic lesions to the pancreas by endoscopic ultrasound‐guided fine needle aspiration
Authors: Krishna Somashekar G , Bhattacharya Abhik , Ross William A , Ladha Harshad , Porter Kyle , Bhutani Manoop S , Lee Jeffrey H
Published: April 2015

Background and Aim

Early diagnosis of solid pancreatic lesions (SPLs) enables prompt treatment. The study aims to identify factors differentiating metastatic lesion to the pancreas (PMET) from pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (PNETs).

Methods

This is a retrospective study at a tertiary cancer center. Consecutive patients referred for endoscopic ultrasound (EUS) of SPLs from 2004 to 2011 were reviewed. The main outcomes were pre‐EUS‐FNA (endoscopic ultrasound‐guided fine needle aspiration) predictors and diagnostic accuracy of EUS‐FNA for PMETs.

Results

Among a total of 1108 EUS‐FNAs for pancreatic lesions, 672 patients had neoplastic SPLs (PMETs = 53; PDACs = 528, PNETs = 91). The sensitivity, specificity, positive predictive value, and accuracy of EUS‐FNA for diagnosis of PMETs were 84.9%, 100%, 100%, and 98.8%, respectively. The mean number of EUS‐FNA passes for diagnosis of PMET was 3.1 per patient. For each endosonographer, preceding 3‐year EUS volume (mean/year) significantly correlated with fewer needle passes (rs[−0.30], P = 0.03). The most common PMET was renal cell carcinoma. Stratified multivariate analyses were performed. Compared with patients with PDACs, PMETs were more common in men (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.0–4.0); located in the pancreatic tail (OR = 2.4; 95%CI = 1.1–5.2); and were less likely with increasing age (OR = 0.95; 95%CI = 0.92–0.99), presence of major symptoms (abdomen pain/diarrhea/weight loss; OR = 0.2; 95%CI = 0.1–0.4), elevated bilirubin (OR = 0.3; 95%CI = 0.13–0.69), and imaging evidence of arterial invasion (OR = 0.15; 95%CI = 0.03–0.67). Compared with PNETs, PMETs were more common with increase age (OR = 1.05; 95%CI = 1.02–1.08) and increasing lesion size (OR = 1.03; 95%CI = 1.0–1.1), and were less likely in patients with diabetes (OR = 0.34; 95%CI = 0.11–0.99).

Conclusion

Among the largest numbers of neoplastic SPLs evaluated at a single center, pre‐test features reliably characterize, and EUS‐FNA provides a highly specific diagnosis of PMETs.
Metabolic abnormalities of gastrointestinal mucosa in celiac disease: An in vitro proton nuclear magnetic resonance spectroscopy study
Authors: Sharma Uma , Upadhyay Deepti , Mewar Sujeet , Mishra Asha , Das Prasenjit , Gupta Siddhartha Datta , Dwivedi Sada Nand , Makharia Govind K , Jagannathan Naranamangalam R
Published: April 2015

Background and Aim

Celiac disease (CeD) is a common autoimmune disorder in which ingestion of gluten and related proteins leads to inflammation in the small intestine. Although the histological findings in CeD are characteristic, they are not specific. In this study, proton nuclear magnetic resonance (NMR) spectroscopy was used to investigate the differences in metabolic profile of duodenal mucosal biopsies of patients with CeD and controls to find out the biomarker/s of villous atrophy.

Methods

Duodenal mucosal biopsies were collected from 29 CeD patients (mean age 26.2 ± 10.8 years) and 17 controls (mean age 34.1 ± 11.1 years) and were subjected to proton NMR spectroscopy following perchloric acid extraction. Assignment of metabolite resonances was carried out and their concentrations were determined. For comparison between the groups unpaired t‐test/Wilcoxon rank sum test was used. Partial least squares‐discriminant analysis was performed to study the clustering behavior of the samples from CeD patients and controls using the Unscrambler 10.2 software.

Results

Partial least squares‐discriminant analysis clearly differentiated CeD patients from controls. Significantly higher concentrations of isoleucine, leucine, aspartate, succinate, and pyruvate, and lower concentration of glycerophosphocholine, were observed in the duodenal mucosa of CeD patients compared with controls. The results suggest abnormalities in glycolysis, Krebs cycle (energy deficiency), and amino acid metabolism, which may affect the biosynthetic pathways and consequently contribute to villous atrophy.

Conclusions

NMR spectroscopy with multivariate analysis of duodenal mucosal biopsies revealed a characteristic metabolic profile in CeD patients. The work provided an insight in determining biomarker/s for villous atrophy and diagnosis of CeD patients.
Endocytosis of GABAC receptors depends on subunit composition and is regulated by protein kinase C‐ζ and protein phosphatase 1
Authors: Linck Lisa , Binder Jasmin , Haynl Christian , Enz Ralf
Published: April 2015

Neuronal excitability depends on the surface concentration of neurotransmitter receptors. Type C gamma‐aminobutyric acid receptors (GABACR) are composed of ρ subunits that are highly expressed in the retina. Molecular mechanisms that guide the surface concentration of this receptor type are largely unknown. Previously, we reported physical interactions of GABACR ρ subunits with protein kinase C‐ζ (PKCζ) via adapter proteins of the ZIP protein family, as well as of protein phosphatase 1 (PP1) via PNUTS. Here, we demonstrate that co‐expressing ρ1 with ZIP3 and PKCζ enhanced basal internalization of GABACR, while receptor internalization was reduced in the presence of PNUTS and PP1. Co‐expression of ρ1 with individual binding partners showed no alterations, except for PP1. Heterooligomeric GABACR composed of ρ1 and ρ2 subunits had a significant higher endocytosis rate than ρ1 containing homooligomeric receptors. Mutant constructs lacking binding sites for protein interactions ensured the specificity of our data. Finally, substitution of serine and threonine residues with alanines indicated that GABACR internalization depends on serine/threonine kinases and phosphatases, but not on tyrosine phosphorylation. We conclude that GABACR internalization is reciprocally regulated by PKCζ and PP1 that are anchored to the receptor via ZIP3 or PNUTS respectively.

image

Endocytosis of GABACR depends on subunit composition and is reciprocally regulated by protein kinase C‐ζ and protein phosphatase 1 that are immobilized to intracellular receptor domains by scaffold proteins (ZIP3, PNUTS). Rho subunits of the pentameric GABACR (grey) offer intracellular phosphorylation sites (P). Our data propose a molecular mechanism that complements available electrophysiological data for GABACR turnover reported in the literature.
Dynamic Contrast‐Enhanced Perfusion MRI and Diffusion‐Weighted Imaging in Grading of Gliomas
Authors: Arevalo‐Perez Julio , Peck Kyung K. , Young Robert J. , Holodny Andrei I. , Karimi Sasan , Lyo John K.
Published: April 2015

PURPOSE

Accurate glioma grading is crucial for treatment planning and predicting prognosis. We performed a quantitative volumetric analysis to assess the diagnostic accuracy of histogram analysis of diffusion‐weighted imaging (DWI) and dynamic contrast‐enhanced (DCE) T1‐weighted perfusion imaging in the preoperative evaluation of gliomas.

METHODS

Sixty‐three consecutive patients with pathologically confirmed gliomas who underwent baseline DWI and DCE‐MRI were enrolled. The patients were classified by histopathology according to tumor grade: 20 low‐grade gliomas (grade II) and 43 high‐grade gliomas (grades III and IV). Volumes‐of‐interest were calculated and transferred to DCE perfusion and apparent diffusion coefficient (ADC) maps. Histogram analysis was performed to determine mean and maximum values for Vp and Ktrans, and mean and minimum values for ADC. Comparisons between high‐grade and low‐grade gliomas, and between grades II, III, and IV, were performed. A Mann‐Whitney U test at a significance level of corrected P ≤ .01 was used to assess differences.

RESULTS

All perfusion parameters could differentiate between high‐grade and low‐grade gliomas (P < .001) and between grades II and IV, grades II and III, and grades III and IV. Significant differences in minimum ADC were also found (P < .01). Mean ADC only differed significantly between high and low grades and grades II and IV (P < .01). There were no differences between grades II and III (P = .1) and grades III and IV (P = .71).

CONCLUSION

When derived from whole‐tumor histogram analysis, DCE‐MRI perfusion parameters performed better than ADC in noninvasively discriminating low‐ from high‐grade gliomas.
The influence of ruthenium on vascular tone
Authors: Pauwels Bart , Boydens Charlotte , Van de Voorde Johan
Published: April 2015

Objectives

Over the past few years, ruthenium has been under attention for development of organometallic drugs with various therapeutic applications. Because of its favourable characteristics, ruthenium is perfectly suitable for drug design. Ruthenium-containing complexes exert a wide range of biological effects. However, so far, the influence of ruthenium itself on vascular tone has never been studied.

Methods

The effect of ruthenium was analysed through organ bath studies measuring isometric tension on mice thoracic aorta. After obtaining a stable contraction plateau, cumulative concentration-response curves of the ruthenium-compounds (RuCl3, Ruthenium Red, [RuCl2(CO)3]2 and RuCl2(DMSO)4) (30–600 μmol/l) were performed. The effect of RuCl3 after contraction with different contractile agents was evaluated. Furthermore, the influence of ruthenium-containing molecules on endogenous (acetylcholine) and exogenous (sodium nitroprusside) NO-mediated relaxations was determined.

Key findings

All studied ruthenium compounds elicit, to some extent, a decrease of the contraction level. Looking further into the underlying mechanism, we found that RuCl3 relaxes aortic rings only when contracted with norepinephrine. This RuCl3-induced relaxation can be prevented by the antioxidants ascorbic acid and N-acetyl L-cysteine. In addition, ruthenium compounds may diminish acetylcholine- or sodium nitroprusside-induced relaxations.

Conclusions

Ruthenium-containing molecules can influence vascular tone induced by norepinephrine due to oxidative inactivation. Moreover, they can undermine NO-mediated responses. This should be considered when developing ruthenium-containing drugs.
Effects of iron–glycine chelate on growth, carcass characteristic, liver mineral concentrations and haematological and biochemical blood parameters in broilers
Authors: Kwiecień M. , Samolińska W. , Bujanowicz‐Haraś B.
Published: April 2015

Studies were carried out to determine the effect of additive iron–glycine chelate on the production performance, slaughter yield, mineral deposition in the liver and the metabolic blood panel in broiler chickens. A total of 250 one‐day‐old Ross 308 chicks were allotted into five groups with five replicates of 10 birds each. Diets were supplemented with the organic form iron (Fe–Gly at the rate of 25%, 50% or 100% of the total requirements of the elements) and inorganic Fe (FeSO4at the rate of 50% or 100%). In the experiment, iron was added to the premix (containing no Fe) in an amount of 40 or 20 mg per kg of basal diet, in groups I andII, in the form of FeSO4, and in an amount of 40, 20 or 10 mg per kg of basal diet, in groupsIII,IVand V, in the form of Fe–Gly. The study covering the period from the first to the 42nd day of breeding revealed that the production performance and slaughter yield were not dependent on the form and amount of added Fe. In the experimental groups with the addition of Fe–Gly of 20 or 10 mg/kg, there were no deaths of chickens during the whole fattening period. As a result, introducing an organic form of iron covering 50% and 25% of the birds' requirement increased the effectiveness of chicken fattening (European Efficiency Index) (p < 0.01). An organic Fe compound (40, 20 or 10 mg/kg) added to mixtures contributed to significant changes in the level of biochemical and haematological indicators in blood. The study demonstrated that an addition of Fe–Gly to mixtures for broilers can be fully effective in terms of production and health performance even if the suggested requirement for this element is 50% or 25% covered.
Alternate‐day dosing of itraconazole in healthy adult cats
Authors: Middleton S. M. , Kubier A. , Dirikolu L. , Papich M. G. , Mitchell M. A. , Rubin S. I.
Published: April 2015

The current available formulations of itraconazole are not ideal for dosing in cats. The capsular preparation often does not allow for accurate dosing, the oral solution is difficult to administer and poorly tolerated, and the bioavailability of compounded formulations has been shown to be poor in other species. The aim of this study was to evaluate every other day dosing of 100 mg itraconazole capsule in healthy adult cats. Ten healthy adult cats received a 100 mg capsule of itraconazole orally every 48 h for 8 weeks. Peak and trough serum concentrations of itraconazole were measured weekly using high‐performance liquid chromatography (HPLC). Physical examination, complete blood count (CBC), and chemistry profiles were performed weekly. The dosage regimen achieved average therapeutic trough concentrations (>0.5 μg/mL) within 3 weeks. The protocol yielded no adverse effects in 8 of the 10 study cats, with affected cats recovering fully with discontinuation of the drug and supportive care. At 8 weeks, an average peak concentration of 1.79 ± 0.952 μg/mL(95%CI: 0.996–2.588) and an average trough concentration of 0.761 ± 0.540 μg/mL(95%CI: 0.314–1.216) were achieved. Overall, a 100 mg every other day oral dosage regimen for itraconazole in cats yielded serum concentrations with minimal fluctuation and with careful monitoring may be considered for treatment of cats with systemic fungal disease.
The danger within: the role of genetic, behavioural and ecological factors in population persistence of colour polymorphic species
Authors: Bolton Peri E. , Rollins Lee A. , Griffith Simon C.
Published: April 2015

Polymorphic species have been the focus of important work in evolutionary biology. It has been suggested that colour polymorphic species have specific evolutionary and population dynamics that enable them to persist through environmental changes better than less variable species. We suggest that recent empirical and theoretical work indicates that polymorphic species may be more vulnerable to extinction than previously thought. This vulnerability arises because these species often have a number of correlated sexual, behavioural, life history and ecological traits, which can have a simple genetic underpinning. When exacerbated by environmental change, these alternate strategies can lead to conflict between morphs at the genomic and population levels, which can directly or indirectly affect population and evolutionary dynamics. In this perspective, we identify a number of ways in which the nature of the correlated traits, their underpinning genetic architecture, and the inevitable interactions between colour morphs can result in a reduction in population fitness. The principles illustrated here apply to all kinds of discrete polymorphism (e.g. behavioural syndromes), but we focus primarily on colour polymorphism because they are well studied. We urge further empirical investigation of the genetic architecture and interactions in polymorphic species to elucidate the impact on population fitness.
The passenger‐associated transport repeat promotes virulence factor secretion efficiency and delineates a distinct autotransporter subtype
Authors: Doyle Matthew Thomas , Tran Elizabeth Ngoc Hoa , Morona Renato
Published: April 2015

Autotransporters are a superfamily of virulence factors secreted by Gram negative bacteria. They are comprised of an N‐terminal passenger domain that is translocated across the outer membrane and a C‐terminal domain that inserts into the outer membrane forming a β‐barrel anchor. It is still poorly understood how the passenger is efficiently translocated in the absence of external energy inputs. Several mechanisms have been proposed in solution of this problem, yet due to the vast diversity of size, sequence and function of the passenger, it is not clear how widely these mechanisms are employed. In this study we functionally characterize a conserved repeat found in many passengers that we designate the Passenger‐associated Transport Repeat (PATR). Using the autotransporter IcsA from the enteropathogen Shigella flexneri, we identified conserved PATR residues that are required for efficient export of the passenger during growth and infection. Furthermore, PATR‐containing autotransporters are significantly larger than non‐PATR autotransporters, with PATR copy number correlating with passenger size. We also show that PATR‐containing autotransporters delineate a subgroup that associates with specific virulence traits and architectures. These results advance our understanding of autotransporter composition and indicate that an additional transport mechanism is important for thousands of these proteins.
A new quorum‐sensing system (TprA/PhrA) for Streptococcus pneumoniae D39 that regulates a lantibiotic biosynthesis gene cluster
Authors: Hoover Sharon E. , Perez Amilcar J. , Tsui Ho‐Ching T. , Sinha Dhriti , Smiley David L. , DiMarchi Richard D. , Winkler Malcolm E. , Lazazzera Beth A.
Published: April 2015

The Phr peptides of the Bacillus species mediate quorum sensing, but their identification and function in other species of bacteria have not been determined. We have identified a Phr peptide quorum‐sensing system (TprA/PhrA) that controls the expression of a lantibiotic gene cluster in the Gram‐positive human pathogen, Streptococcus pneumoniae. Lantibiotics are highly modified peptides that are part of the bacteriocin family of antimicrobial peptides. We have characterized the basic mechanism for a Phr‐peptide signaling system in S. pneumoniae and found that it induces the expression of the lantibiotic genes when pneumococcal cells are at high density in the presence of galactose, a main sugar of the human nasopharynx, a highly competitive microbial environment. Activity of the Phr peptide system is not seen when pneumococcal cells are grown with glucose, the preferred carbon source and the most prevalent sugar encountered by S. pneumoniae during invasive disease. Thus, the lantibiotic genes are expressed under the control of both cell density signals via the Phr peptide system and nutritional signals from the carbon source present, suggesting that quorum sensing and the lantibiotic machinery may help pneumococcal cells compete for space and resources during colonization of the nasopharynx.
Pimpinella rhomboidea var. tenuiloba is a synonym of Melanosciadium bipinnatum (Apiaceae)
Authors: Tan Jin‐Bo , Wang Zhi‐Xin , Xie Deng‐Feng , He Xing‐Jin
Published: April 2015

Based on field investigations, as well as investigation of relevant specimens, Pimpinella rhomboidea var. tenuiloba is shown to be conspecific with Melanosciadium bipinnatum. The distribution and habitat of M. bipinnatum is redescribed and notes on the taxonomy of the species are presented.