bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple clear‐cell acanthomas
Authors: Martínez Escanamé Marcela , Arzberger Edith , Hofmann‐Wellenhof Rainer , Massone Cesare
Published: August 2013

Clear‐cell acanthoma (CCA) usually presents as a solitary lesion involving the lower extremities. The abrupt onset of multiple CCA has been rarely reported. Such presentation may impose clinical diagnostic and therapeutic challenges. A 52‐year‐old man with multiple CCA is presented in this communication. The value of dermoscopy has been demonstrated in the setting of CCA. However, because of the unusual clinical presentation reflecting confocal microscopy was also performed in this case to enhance the accuracy of the clinical and dermoscopic diagnosis.
Properties of submucosal venules in the rat distal colon
Authors: Mitsui Retsu , Miyamoto Shun , Takano Hiromichi , Hashitani Hikaru
Published: August 2013

Background and Purpose

Venules within the gut wall may have intrinsic mechanisms for maintaining the circulation even upon the intestinal wall distension. We aimed to explore spontaneous and nerve‐mediated contractile activity of colonic venules.

Experimental Approach

Changes in the diameter of submucosal venules of the rat distal colon were measured using video microscopy. The innervation of the microvasculature was investigated using fluorescence immunohistochemistry.

Key Results

Submucosal venules exhibited spontaneous constrictions that were abolished by blockers of L‐type Ca2+ channels (1 μM nicardipine), Ca2+‐ATPase (10 μM cyclopiazonic acid), IP3 receptor (100 μM 2‐APB), Ca2+‐activated Cl− channels (100 μM DIDS) or store‐operated Ca2+ entry channels (10 μM SKF96365). Transmural nerve stimulation (TNS at 10 Hz) induced a phasic venular constriction that was blocked by phentolamine (1 μM, α‐adrenoceptor antagonist) or sympathetic nerve depletion using guanethidine (10 μM). Stimulation of primary afferent nerves with TNS (at 20 Hz) or capsaicin (100 nM) evoked a sustained venular dilatation that was attenuated by calcitonin gene‐related peptide (CGRP) 8‐37 (2 μM), a CGRP receptor antagonist. Immunohistochemistry revealed sympathetic and primary afferent nerves running along submucosal venules.

Conclusions and Implications

Submucosal venules of the rat distal colon exhibit spontaneous constrictions that appear to primarily rely on Ca2+ release from sarcoplasmic reticulum and subsequent opening of Ca2+‐activated Cl– channels that trigger Ca2+ influx through L‐type Ca2+ channels. Venular contractility is modulated by sympathetic as well as CGRP‐containing primary afferent nerves, suggesting that submucosal venules may play an active role in regulating the microcirculation of the digestive tract.
An in vitro model for the pro‐fibrotic effects of retinoids: mechanisms of action
Authors: Rankin A C , Hendry B M , Corcoran J P , Xu Q
Published: August 2013

Background and Purpose

Retinoids, including all‐trans retinoic acid (tRA), have dose‐dependent pro‐fibrotic effects in experimental kidney diseases. To understand and eventually prevent such adverse effects, it is important to establish relevant in vitro models and unravel their mechanisms.

Experimental Approach

Fibrogenic effects of retinoids were assessed in NRK‐49F renal fibroblasts using picro‐Sirius red staining for collagens and quantified by spectrophotometric analysis of the eluted stain. Other methods included RT‐qPCR, immunoassays and matrix metalloproteinase (MMP) activity assays.

Key Results

With or without TGF‐β1, tRA was dose‐dependently pro‐fibrotic, notably increasing collagen accumulation. tRA and TGF‐β1 additively suppressed expression of mRNA for MMP2, 3 and 13 and suppressed MMP activity. tRA, in the presence of TGF‐β1, induced plasminogen activator inhibitor‐1 (PAI‐1) mRNA and they additively induced PAI‐1 protein expression. A PAI‐1 inhibitor, a pan‐retinoic acid receptor (RAR) antagonist and a pan‐retinoid X receptor (RXR) antagonist each partially prevented the pro‐fibrotic effect of tRA. The dose‐dependent pro‐fibrotic effects of a pan‐RXR agonist were similar to those of tRA. A pan‐RAR agonist showed weaker, less dose‐dependent pro‐fibrotic effects and the pro‐fibrotic effects of RARα and RARβ‐selective agonists were even smaller. An RARγ‐selective agonist did not affect fibrogenesis.

Conclusions and Implications

An in vitro model for the pro‐fibrotic effects of retinoids was established in NRK‐49F cells. It was associated with reduced MMP activity and increased PAI‐1 expression, and was probably mediated by RXR and RAR. To avoid or antagonize the pro‐fibrotic activity of tRA, further studies on RAR isotype‐selective agonists and PAI‐1 inhibitors might be of value.
Neuropeptide Y and peptide YY protect from weight loss caused by Bacille Calmette–Guérin in mice
Authors: Painsipp Evelin , Köfer Martin J , Farzi Aitak , Dischinger Ulrich S , Sinner Frank , Herzog Herbert , Holzer Peter
Published: August 2013

Background and Purpose

Immune challenge of mice with Bacille Calmette–Guérin (BCG) has been reported to cause transient weight loss and a behavioural sickness response. Although BCG‐induced depression involves the kynurenine pathway, weight loss occurs independently of this factor. Because neuropeptide Y (NPY) and peptide YY (PYY) are involved in the regulation of food intake, we hypothesized that they play a role in the BCG‐induced weight loss.

Experimental Approach

Male wild‐type, PYY knockout (PYY−/−), NPY knockout (NPY−/−) and NPY−/−;PYY−/− double knockout mice were injected with vehicle or BCG (approximately 108 colony‐forming units per mouse), and their weight, locomotion, exploration and ingestion were recorded for 2 weeks post‐treatment.

Key Results

Deletion of PYY and NPY aggravated the BCG‐induced loss of body weight, which was most pronounced in NPY−/−;PYY−/− mice (maximum loss: 15%). The weight loss in NPY−/−;PYY−/− mice did not normalize during the 2 week observation period. BCG suppressed the circadian pattern of locomotion, exploration and food intake. However, these changes took a different time course than the prolonged weight loss caused by BCG in NPY−/−;PYY−/− mice. The effect of BCG to increase circulating IL‐6 (measured 16 days post‐treatment) remained unaltered by knockout of PYY, NPY or NPY plus PYY.

Conclusions and Implications

These data show that NPY and PYY are both required to protect from the action of BCG‐evoked immune challenge to cause prolonged weight loss and disturb energy balance. The findings attest to an important role of NPY and PYY in orchestrating homeostatic reactions to infection and immune stimulation.
Evaluation of the insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta‐cells, isolated pancreatic islets and mice
Authors: McKillop A M , Moran B M , Abdel‐Wahab Y H A , Flatt P R
Published: August 2013

Background and Purpose

G‐protein coupled receptor (GPR)55 is a novel lipid sensing receptor activated by both cannabinoid endogenous ligands (endocannabinoids) and other non‐cannabinoid lipid transmitters. This study assessed the effects of various GPR55 agonists on glucose homeostasis.

Experimental Approach

Insulin secretion and changes in intracellular Ca2+ and cAMP in response to glucose and a range of GPR55 agonists [endogenous ligands (OEA, PEA), chemically synthetic cannabidiol (CBD) analogues (Abn‐CBD, 0–1602), an analogue of rimonabant (AM‐251) and antagonist (CBD)] were investigated in clonal BRIN‐BD11 cells and mouse pancreatic islets. Cytotoxicity was assessed by LDH release, cellular localization by double‐staining immunohistochemistry and in vivo effects assessed in mice.

Key Results

The most potent and selective GPR55 agonist was the synthetic CBD analogue, Abn‐CBD (pEC50 10.33), maximum stimulation of 67% at 10−4 mol·L−1 (P < 0.001) in BRIN‐BD11 cells. AM‐251 (pEC50 7.0), OEA (pEC50 7.0), 0–1602 (pEC50 7.3) and PEA (pEC50 6.0) stimulated insulin secretion. Results were corroborated by islet studies, with no cytotoxic effects. Concentration‐dependent insulin secretion by GPR55 agonists was glucose‐sensitive and accompanied by elevations of [Ca2+]i (P < 0.01–P < 0.001) and cAMP (P < 0.05–P < 0.01). GPR55 agonists exhibited insulinotropic and glucose lowering activity in vivo. GPR55 was expressed on BRIN‐BD11 cells and confined to islet beta cells with no distribution on alpha cells.

Conclusion and Implications

These results demonstrate GPR55 is distributed in pancreatic beta cells and is a strong activator of insulin secretion, with glucose‐lowering effects in vivo. Development of agents agonizing the GPR55 receptor may have therapeutic potential in the treatment of type 2 diabetes.
Neuronal AChE splice variants and their non‐hydrolytic functions: redefining a target of AChE inhibitors?
Authors: Zimmermann M
Published: August 2013

AChE enzymatic inhibition is a core focus of pharmacological intervention in Alzheimer's disease (AD). Yet, AChE has also been ascribed non‐hydrolytic functions, which seem related to its appearance in various isoforms. Neuronal AChE presents as a tailed form (AChE‐T) predominantly found on the neuronal synapse, and a facultatively expressed readthough form (AChE‐R), which exerts short to medium‐term protective effects. Notably, this latter form is also found in the periphery. While these non‐hydrolytic functions of AChE are most controversially discussed, there is evidence for them being additional targets of AChE inhibitors. This review aims to provide clarification as to the role of these AChE splice variants and their interplay with other cholinergic parameters and their being targets of AChE inhibition: AChE‐R is particularly involved in the mediation of (anti‐)apoptotic events in cholinergic cells, involving adaptation of various cholinergic parameters and a time‐dependent link to the expression of neuroprotective factors. The AChE‐T C‐terminus is central to AChE activity regulation, while isolated AChE‐T C‐terminal fragments mediate toxic effects via the α7 nicotinic acetylcholine receptor. There is direct evidence for roles of AChE‐T and AChE‐R in neurodegeneration and neuroprotection, with these roles involving AChE as a key modulator of the cholinergic system: in vivo data further encourages the use of AChE inhibitors in the treatment of neurodegenerative conditions such as AD since effects on both enzymatic activity and the enzyme's non‐hydrolytic functions can be postulated. It also suggests that novel AChE inhibitors should enhance protective AChE‐R, while avoiding the concomitant up‐regulation of AChE‐T.
The moral imperatives of geographies of school failure: Mobilizing market‐based reform coalitions
Authors: Lizotte Christopher
Published: August 2013

School reform efforts in the United States often declare the entire institution irreparably unresponsive to student needs and in need of a fundamental overhaul. Consequently, coalitions that incorporate business and philanthropic actors have advocated strongly for the introduction of market logics into the public system. I argue that these movements are facilitated by creating a sense of obligation that is mapped onto the space of the urban or metropolitan area. I draw on archival research and open‐ended interviews to demonstrate the degree to which this moral obligation dominates reform efforts in the Seattle area through two coalitions: the first, made up of local business, philanthropic, and citizen groups that advocate for introducing market logics of choice and accountability, and the second, made up of parents who advocate for a network of alternative schools that meet the needs of students not served by the public system. Based on these differences, I argue that the former coalition's greater influence is in part due to its ability to mobilize an image of urgency around school reform that is geographically specific even as it glosses over differences in the spaces of education quality within the larger Seattle area.
Education in global Chicago and the remaking of contemporary capitalism
Authors: Brogan Peter
Published: August 2013

This article examines the role that transformations in the K‐12 public education sector have played in the ongoing structural crisis of contemporary capitalism and the re/making of North American global cities. More specifically, it explores why and how teachers’ unions have been at the centre of the neoliberalization of public school systems by drawing on a case‐study analysis of Chicago, which has been an experimental ground for the reconstruction of urban governance, labour markets, and education. Like the marketization of public housing, education markets contribute to the knitting together of education policy and neoliberal urban development. Underlying the assault on public education, teachers, and their unions in the United States are the intermingling logics of capital accumulation and white supremacy. Although teachers’ unions have often been complicit in the making of neoliberalism, they also represent the biggest potential challenge to its further advancement through the adoption of a model of social justice, grassroots unionism. Offering a powerful glimmer of hope is the revitalized Chicago Teachers Union who waged an effective—and widely supported—September 2012 strike.
Clinical characteristics of Graves' orbitopathy in patients showing discrepancy between levels from TBII assays and TSI bioassay
Authors: Jang Sun Young , Shin Dong Yeob , Lee Eun Jig , Yoon Jin Sook
Published: August 2013

Objective

To investigate clinical characteristics of patients with Graves' orbitopathy (GO) who showed discrepancies between levels of thyroid‐stimulating immunoglobulin (TSI) and thyrotropin‐binding inhibitory immunoglobulin (TBII).

Design

Comparative case series.

Patients

A total of 317 patients with GO in whom Mc4‐TSI and M22‐TRAb (third‐generation TBII) were measured simultaneously. Patients were divided into four groups according to TRAb levels as followings: Group 1, TBII and TSI < median value; Group 2, TBII ≥ median, TSI < median; Group 3, TBII < median, TSI ≥ median; Group 4, both TBII and TSI ≥ median.

Measurement

Endocrine and ophthalmic clinical manifestations in each group.

Results

The median value of M22‐TRAb was 6·11 IU/l and that of Mc4‐TSI was 415·1 (SRR%). One hundred seventeen patients were classified as Group 1, 41 patients as Group 2, 41 patients as group 3 and 118 patients as group 4. Mean CAS was significantly higher in Groups 3 (2·2) and 4 (2·2) than in Groups 1 (1·6) and 2 (1·4; P = 0·001, anova). Mean modified NOSPECS scores were significantly higher (P < 0·001, anova) in Groups 3 (4·1) and 4 (4·1) than in Groups 1 (3·1) and 2 (2·3). The proportion of patients with hyperthyroidism was larger in Group 2 (85·4% [35/41 patients]) than in Group 3 (48·8% [20/41 patients]; P = 0·002).

Conclusions

GO is more active and severe in patients with predominant Mc4‐TSI than in patients with predominant M22‐TRAb. Patients with hyperthyroidism were more likely to be included with patients with predominant M22‐TRAb than with predominant Mc4‐TSI.
Treated and untreated women with idiopathic precocious puberty: long‐term follow‐up and reproductive outcome between the third and fifth decades
Authors: Lazar Liora , Meyerovitch Joseph , de Vries Liat , Phillip Moshe , Lebenthal Yael
Published: August 2013

Context

Central precocious puberty (CPP), treated or untreated, may have implications in adulthood.

Objective

To assess the reproductive outcome and social adjustment of former CPP women between the 3rd and 5th decades of life.

Design

Cross‐sectional study of an historical cohort.

Methods

Demographic data and gynaecological history of 214 CPP women aged 25–56 years [135 GnRH analogue (GnRHa)‐treated, 18 cyproterone acetate (CyA)‐treated, 61 untreated] and of 446 controls with normal puberty, matched for age and year of birth, were recorded in a structured interview.

Results

Marital status, education and number of children were similar in CPP women and controls. Clinical hyperandrogenism (acne/hirsutism with oligomenorrhoea) was more frequently reported in CPP women than in controls: GnRHa‐treated 29·6% vs 17·4% (P = 0·006), CyA‐treated 50% vs 20·4% (P = 0·04), untreated 34·4% vs 17·2% (P = 0·003), with no significant difference between CPP groups. Spontaneous pregnancy was similarly achieved by treated CPP and controls: GnRHa‐treated 90·4% vs 93·4%, CyA‐treated 86·7% vs 90·2%. Assisted fertilization rate was higher in untreated CPP than treated CPP groups (P = 0·006) and controls (P = 0·03). Untreated CPP was the only parameter associated with clinical hyperandrogenism (OR=2·04, 95% CI, 1·0–4·16, P = 0·07) and fertility problems (OR=3·40, 95% CI, 1·15–10·0, P = 0·047). Course of pregnancy was uneventful in 90·2% of CPP women and 90·9% of controls.

Conclusions

The increased rate of clinical hyperandrogenism among CPP women implies that the underlying neuroendocrine dysfunction persists into adult life. Pubertal suppression treatment may have a protective effect as fertility problems were more prevalent only among untreated CPP women. Educational achievements and marital status were unaffected by CPP.
Adrenal ganglioneuroma: features and outcomes of 27 cases at a referral cancer centre
Authors: Shawa Hassan , Elsayes Khaled M. , Javadi Sanaz , Morani Ajaykumar , Williams Michelle D. , Lee Jeffrey E. , Waguespack Steven G. , Busaidy Naifa L. , Vassilopoulou‐Sellin Rena , Jimenez Camilo , Habra Mouhammed Amir
Published: August 2013

Background

Adrenal ganglioneuroma (AGN) is a rare neurogenic tumour that can mimic other adrenal neoplasms. Limited information, mostly derived from small cases series, is available for AGN.

Methods

A retrospective review for AGNs seen at a tertiary referral centre describing important features to distinguish AGN from other adrenal neoplasms.

Results

Of 53 ganglioneuromas, 27 were AGNs. Median age was 31 years (range, 1·7–64 years) and median tumour size was 8 cm (range, 1·5–20 cm). Seventeen AGNs (63%) were detected incidentally and nine patients (33%) presented with abdominal/back discomfort. Catecholamine levels, available for 21 patients, were normal. On computed tomography (CT), most AGNs were homogenous and well circumscribed with a median density of 32·5 Hounsfield units (HU) on unenhanced CT; 40 HU on postcontrast venous phase; and 66·5 HU on delayed postcontrast phase. On magnetic resonance imaging (MRI), AGNs had hypo‐intense signal on T1‐weighted images with heterogeneous hyperintense signal on T2‐weighted images. In four patients, there was no tumour growth during median follow‐up of 48 months (range, 21–60 months). One patient had malignant peripheral nerve sheath tumour arising from AGN. Thirteen patients with resected AGN had no recurrence during a median follow‐up of 50 months (range, 2–135 months).

Conclusions

We herein describe the largest AGN series reported to date. Isolated AGNs do not produce catecholamines and have CT imaging characteristics that can help in distinguishing them from other adrenal and para‐adrenal neoplasms. The natural history of AGNs is usually benign, although local extra‐adrenal extension or malignant transformation can rarely occur.
Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome
Authors: Schrauwen I. , Sommen M. , Claes C. , Pinner J. , Flaherty M. , Collins F. , Van Camp G.
Published: August 2013

Two siblings, from a consanguineous Iraqi family, were investigated to identify the underlying genetic cause of their high myopia, esotropia, vitreous changes and cataract. Subsequent investigation identified low molecular weight proteinuria as part of their syndrome. Exome sequencing of one of the probands revealed a new non‐synonymous variant in the LRP2 gene. Sanger sequencing confirmed the mutation and segregation in the family. No mutation was identified in COL9A1/2, COL11A1/2, or COL2A1 genes. The variant (c.11483A>G; p.Asp3828Gly) is predicted to be damaging and is conserved among vertebrate species. Mutations in LRP2 have been shown to cause the Donnai–Barrow syndrome (DBS) or facio‐oculo‐acoustico‐renal (FOAR) syndrome, a syndrome associated with facial dysmorphism, ocular anomalies, sensorineural hearing loss, low molecular weight proteinuria, and diaphragmatic hernia and absent corpus callosum, although there is variability in the expression of some features. This family shows a milder phenotype with a predominant eye phenotype similar to the Stickler syndrome and only a few features of the DBS, including microglobulinuria. The presence of microglobulinuria was only detected after molecular results were known. In conclusion, with the identification of a new mutation in LRP2 associated with a predominant eye phenotype similar to the Stickler syndrome, we have broadened the phenotypic spectrum of LRP2 mutations.
Design and Fabrication of Faceted Mirror Arrays for Light Field Capture
Authors: Fuchs Martin , Kächele Markus , Rusinkiewicz Szymon
Published: August 2013

The high resolution of digital cameras has made single‐shot, single‐sensor acquisition of light fields feasible, though considerable design effort is still necessary in order to construct the necessary collection of optical elements for particular acquisition scenarios. This paper explores a pipeline for designing, fabricating and utilizing faceted mirror arrays which simplifies this task. The foundation of the pipeline is an interactive tool that automatically optimizes for mirror designs while exposing to the user a set of intuitive parameters for light field quality and manufacturing constraints. We investigate two manufacturing processes for automatic fabrication of the resulting designs: one is based on CNC milling, polishing, and plating of one solid work piece, while the other involves assembly of CNC‐cut mirror facets. We demonstrate results for refocusing in a macro photography scenario. In addition, we observe that traditional photographic parameters take novel roles in the faceted mirror array setup and discuss their influence.
Histopathology of body art revisited – analysis and discussion of 19 cases
Authors: Körner Rebecca , Pföhler Claudia , Vogt Thomas , Müller Cornelia S. L.
Published: August 2013

Background and Objectives

With the number of tattoos increasing, a rising number of complications have also been reported, such as allergic and foreign body reactions or the development of malignant tumors. We discuss 19 patients with alterations in skin tattoos, define clinicopathologic characteristics and give a brief review of the literature.

Patients and Methods

Biopsy specimens were obtained in 13 of 19 patients. In all cases, staining was performed with hematoxylin‐eosin, periodic acid‐Schiff, CD68, CD123, and CD163. The inflammatory infiltrate was classified according to the pattern analysis of Ackerman.

Results

Three of 19 patients (15.8%) had temporary tattoos with henna and 16 (84.2%) had permanent tattoos. Histologically, among the 13 biopsy specimens we found signs of acute contact dermatitis in 2 (15.3%), lupus‐like patterns in 2 (15.3%), foreign body dermatitis in 5 (38.4%), deposition of pigment without inflammation or simple scarring in 2 (15.3%), and tumors in 2 patients (15.2%), 1 of which was a malignant melanoma.

Conclusions

Clinical presentation frequently, but not always, correlates with the histologic pattern. Obtaining a biopsy can be helpful in determining further investigations, for example allergy testing or a search for systemic involvement in cases of tattoo sarcoidosis.
Do data in the literature indicate that glycaemic variability is a clinical problem? Glycaemic variability and vascular complications of diabetes
Authors: Cavalot F.
Published: August 2013

In recent years glycaemic variability (GV) has emerged as a determinant of vascular complications of both type 1 and type 2 diabetes mellitus. In type 1 diabetes analysis of data of GV show conflicting results on both micro‐ and macro‐vascular complications. In non‐diabetic subjects blood glucose after loading is a stronger predictor of cardiovascular complications than fasting glucose. In type 2 diabetes both coefficient of variation of fasting blood glucose and postprandial blood glucose predict cardiovascular events. Also, long term variability of HbA1c has been associated predominantly with diabetic nephropathy, less frequently with retinopathy. Intervention trials to evaluate the effect of postprandial glucose have been conducted only in prediabetes or in type 2 diabetes and the data are not conclusive. In vitro and in vivo data have shown the mechanisms that are at the basis of the adverse cardiovascular effects of GV, mainly associated with oxidative stress; the atherogenic action of postprandial glucose also involves insulin sensitivity, postprandial increase in serum lipids and glycaemic index of food. Thus, correction of GV emerges as a target to be pursued in clinical practice in order to safely reduce mean blood glucose (and thus glycated haemoglobin) and for its direct effects on vascular complications of diabetes.
How can we monitor glycaemic variability in the clinical setting?
Authors: Inchiostro S. , Candido R. , Cavalot F.
Published: August 2013

No universal consensus exists on how to express glycaemic variability. Among other parameters, standard deviation of blood glucose values, mean amplitude of glycaemic excursions (MAGE), the Low Blood Glucose Index (LBGI) and the High Blood Glucose Index (HBGI), which were subsequently combined into the Average Daily Risk Range (ADRR), mean of daily differences (MODD) and glycaemic variability index (GVI) are highlighted. The continuous glucose monitoring in research and clinical settings has been a great help for a comprehensive approach to circadian blood glucose evaluation and identification of individual patterns, mainly in type 1 diabetes, but recently also in type 2 diabetes. In everyday clinical practice the judicious use of self‐monitoring of blood glucose in an educational setting involving the patient and the care team is an unreplaceable tool to effectively and safely guide behavioural and drug therapy.
Losing Oneself (in a Good Way): On the Value of Full Attention
Authors: Debus Dorothea
Published: August 2013

The present paper considers the question whether, and if so how, a subject's full attention to an object which she interacts with might have value. More specifically,Idefend the claim that in order for a subject's activity to have value, it issufficientthat the subject give her full attention to the object towards which the activity is directed.
Epilepsy in individuals with neurofibromatosis type 1
Authors: Ostendorf Adam P. , Gutmann David H. , Weisenberg Judith L. Z.
Published: August 2013

Purpose

To describe the clinical characteristics and outcomes of individuals with neurofibromatosis type 1 (NF1) and seizures in the largest cohort reported to date.

Methods

A retrospective cross‐sectional review of 536 individuals with NF1 was performed, and clinical data from 51 individuals with a history of at least one seizure were analyzed.

Key Findings

In individuals with NF1, 9.5% had a history of at least one unprovoked seizure, and 6.5% had documented epilepsy. Individuals with seizures were more likely to have inherited NF1 from their mother (p = 0.001). Focal seizures were the most common type, occurring in 57% of individuals, although generalized seizures, specific electroclinical syndromes, and the presence of multiple seizure types were also noted. Moreover, in 21% of individuals with a previously unremarkable magnetic resonance imaging (MRI) study, neuroimaging at seizure onset revealed a new structural abnormality. In this population, 77% of individuals required multiple antiepileptic drugs (AEDs), and some required epilepsy surgery, with the best results following temporal lobe glioma resection.

Significance

Compared to the general population, seizures are more common in individuals with NF1, where they are often focal and related to an intracranial neoplasm. These observations suggest that all individuals with NF1 and a new seizure should undergo MRI despite previous normal neuroimaging. Individuals with seizures and NF1 typically require more aggressive therapy than those without NF1 and should be considered for epilepsy surgery when appropriate.
The nature and origin of nucleus‐like intracellular inclusions in Paleoproterozoic eukaryote microfossils
Authors: Pang K. , Tang Q. , Schiffbauer J. D. , Yao J. , Yuan X. , Wan B. , Chen L. , Ou Z. , Xiao S.
Published: August 2013

The well‐known debate on the nature and origin of intracellular inclusions (ICIs) in silicified microfossils from the early Neoproterozoic Bitter Springs Formation has recently been revived by reports of possible fossilized nuclei in phosphatized animal embryo‐like fossils from the Ediacaran Doushantuo Formation of South China. The revisitation of this discussion prompted a critical and comprehensive investigation of ICIs in some of the oldest indisputable eukaryote microfossils—the ornamented acritarchs Dictyosphaera delicata and Shuiyousphaeridium macroreticulatum from the Paleoproterozoic Ruyang Group of North China—using a suite of characterization approaches: scanning electron microscopy (SEM), transmission electron microscopy (TEM), and focused ion beam scanning electron microscopy (FIB‐SEM). Although the Ruyang acritarchs must have had nuclei when alive, our data suggest that their ICIs represent neither fossilized nuclei nor taphonomically condensed cytoplasm. We instead propose that these ICIs likely represent biologically contracted and consolidated eukaryotic protoplasts (the combination of the nucleus, surrounding cytoplasm, and plasma membrane). As opposed to degradational contraction of prokaryotic cells within a mucoidal sheath—a model proposed to explain the Bitter Springs ICIs—our model implies that protoplast condensation in the Ruyang acritarchs was an in vivo biologically programmed response to adverse conditions in preparation for encystment. While the discovery of bona fide nuclei in Paleoproterozoic acritarchs would be a substantial landmark in our understanding of eukaryote evolution, the various processes (such as degradational and biological condensation of protoplasts) capable of producing nuclei‐mimicking structures require that interpretation of ICIs as fossilized nuclei be based on comprehensive investigations.
Rain use efficiency as affected by climate warming and biofuel harvest: results from a 12‐year field experiment
Authors: Yan Liming , Luo Yiqi , Sherry Rebecca A. , Bell Jesse E. , Zhou Xuhui , Xia Jianyang
Published: August 2013

The efficiency of a terrestrial ecosystem to use rainfall in production is critical in regulating the ecological functions of the earth system under global change. However, it remains unclear how rain use efficiency (RUE) will be altered by changes in climate and human activities such as biofuel harvest. In this study, we used RUE data from a long‐term experiment in a tallgrass prairie to analyze the effects of warming and biofuel harvest (clipping). From 2000 to 2011, experimental warming enhanced RUE in most years, with larger positive effects in normal and wet than dry hydrological years. Clipping decreased RUE in dry and normal hydrological years, but had no impact on RUE in wet years. The observed RUE responses resulted from treatment‐induced changes in both biologically ineffective (i.e., runoff and soil evaporation) and effective (i.e., transpiration) parts of precipitation. For example, litter cover was increased in warming plots, but reduced by clipping, leading to negative and positive effects on runoff and soil evaporation, respectively. The dominance of C4 species, which usually have higher water use efficiency than C3 species, was enhanced by warming, but reduced by clipping. Moreover, RUE was positively correlated with ratios of rainfall in the late growing season (June–August), when the growth of C4 plants was most active, relative to that in the other seasons. Our results indicate that RUE is positively influenced by climate warming, but negatively affected by biofuel harvest in tallgrass prairie of the Great Plains. These findings highlight the important roles of plant community structure and temporal distribution of precipitation in regulating ecosystem RUE.
Dementia diagnosis and osteoporosis treatment propensity: A population‐based nested case–control study
Authors: Knopp‐Sihota Jennifer A , Cummings Greta G , Newburn‐Cook Christine V , Homik Joanne , Voaklander Don
Published: August 2013

Aim

Increasing age and a diagnosis of dementia both dramatically increase the risk of serious osteoporosis‐related sequela. We sought to examine the factors associated with osteoporosis treatment, in relation to dementia diagnosis, in older adults with osteoporosis.

Methods

This was a population‐based, retrospective, nested, case–control study utilizing administrative healthcare data fromBritishColumbia,Canada.Community‐based individuals aged ≥65 years with an osteoporosis diagnosis and continuous enrolment in the provinces' drug plan between 1991 and 2007 were eligible for inclusion. A multivariate logistic regression model was assembled to examine the relationship between dementia diagnosis, age, sex, other comorbidity, residence and osteoporosis medication dispensation.

Results

Almost half of the total osteoporosis cohort (n = 39 452) were dispensed an osteoporosis medication during the study period. Individuals with no dementia diagnosis were dispensed a medication significantly more often than those with a diagnosis of dementia (P < 0.001). Those patients with dementia (n = 13 315), who had been dispensed an osteoporosis drug, were more often younger, female, had not sustained a previous fracture, had ≥ 4 comorbid conditions and lived in the most central health region (P < 0.001). A diagnosis of dementia was found to be a significant negative predictor of osteoporosis drug dispensation (adjustedOR0.55; 95%CI0.44–0.69). Increasing comorbidity was significantly associated with receiving treatment (adjustedOR3.30; 95%CI2.88–3.78).

Conclusion

Despite the wide availability of osteoporosis medications, our findings suggest that many older adults with a diagnosis of dementia, but not necessarily fewer comorbid conditions, were not receiving treatment.GeriatrGerontol Int 2014; 14: 121–129.
Neighborhood attributes security and solidarity promote the well‐being of community‐dwelling older people in the Netherlands
Authors: Cramm Jane M , Nieboer Anna P
Published: August 2013

Aim

To determine whether the neighborhood attributes solidarity and security positively affect the well‐being of community‐dwelling older people in the Netherlands after accounting for individual characteristics, and to test if a higher level of security in combination with a stronger sense of neighborhood solidarity results in a higher level of well‐being.

Methods

The study sample for the cross‐sectional study consisted of 869 out of 2212 (39% response rate) independently‐living older adults (aged >70 years) in 92 neighborhoods of Rotterdam. We fitted a hierarchical random‐effects model to account for the structure of the study design: 869 older people (level 1) nested in 92 neighborhoods (level 2) in 10 districts (level 3).

Results

Neighborhood security and solidarity among neighbors varied significantly among the 10 districts. Univariate analyses showed that education, income, neighborhood security and solidarity within neighborhoods (all P ≤ 0.001) were significantly related to the well‐being of community‐dwelling older people. Multilevel analyses showed neighborhood security and solidarity within neighborhoods predicted the well‐being of community‐dwelling older people. Furthermore, a positive interaction effect was found between neighborhood security and solidarity within neighborhoods, and well‐being of community‐dwelling older people.

Conclusions

Neighborhood security and solidarity among neighbors are important for the well‐being of community‐dwelling older people. Furthermore, neighborhoods with high levels of perceived security in combination with stronger solidarity among neighbors are especially beneficial to the well‐being of community‐dwelling older people. Geriatr Gerontol Int 2014; 14: 681–688.
Use of thromboelastography and thrombin generation assay to predict clinical phenotype in patients with severe FVII deficiency
Authors: Tran H. T. T. , Tjønnfjord G. E , Holme P. A.
Published: August 2013

Bleeding tendency is weakly correlated with the activity of factor VII (FVII) in the plasma of patients with FVII deficiency. A laboratory method for predicting bleeding risk in patients with this coagulation disorder is lacking. We investigated whether global coagulation assays, specifically thromboelastography (TEG) and thrombin generation assay (TGA), could be used to predict bleeding risk. We also sought to identify factors that may explain the differences in bleeding phenotype observed among individuals with severe FVII deficiency. The study comprised 12 patients with severe FVII deficiency (FVII activity <1%). Eleven patients were homozygous for the Gln100Arg mutation and one patient was compound heterozygous. Clinically, 10 patients had increased haemorrhagic diathesis, whereas two patients were asymptomatic. Blood sampling was performed at baseline for TEG and TGA analyses. The platelet aggregation assay was performed and the plasma level of anticoagulation inhibitors and thrombophilic risk factors assessed. No difference in the TEG and TGA results was observed in all FVII‐deficient individuals. The level of free tissue factor pathway inhibitor was within the normal range and similar in symptomatic and asymptomatic subjects. None of the participants had the FV Leiden mutation, prothrombin gene mutation, or abnormal anticoagulant inhibitor levels. Asymptomatic subjects showed normal platelet aggregation. These data suggested that TEG and TGA were not suitable methods for predicting the clinical phenotype in FVII‐deficient subjects.
Determination of phosphorylated proteins in tissue specimens requires high‐quality samples collected under stringent conditions
Authors: Wolf Corinna , Jarutat Tiantom , Vega Harring Suzana , Haupt Kristin , Babitzki Galina , Bader Sabine , David Kerstin , Juhl Hartmut , Arbogast Susanne
Published: August 2013

Aims

For selection of patients who will benefit from targeted therapies, identification of biomarkers predictive of treatment response is desirable. Activation of the targeted pathway becomes apparent by protein phosphorylation. Determination of this phenomenon is therefore considered a promising biomarker approach. To date, however, it is unclear whether routinely collected tissue specimens allow determination of in‐vivo phosphorylation states.

Methods and results

To investigate whether routinely collected tissue specimens retain the true phosphorylation states of a tumour's proteins, we compared protein phosphorylation states between matched tumour samples that were subjected to different ischaemic times by immunohistochemistry. The influence of formalin fixation and paraffin‐embedding on phosphorylation states was investigated by comparison of matched fresh frozen and formalin‐fixed paraffin‐embedded surgical specimens as well as small biopsies. We show that ischaemia influences protein phosphorylation in a tumour‐specific, unpredictable manner. Formalin fixation and paraffin‐embedding lead to a decrease in detectable protein phosphorylation in larger surgical specimens, but not in small biopsies.

Conclusions

Determination of protein phosphorylation using routinely collected surgical specimens results in artefacts which do not reflect a tumour's true states of pathway activation. Valid measurement of phosphorylated biomarkers requires that tissue collection procedures are tightly controlled, avoiding ischaemia and large‐specimen fixation.
The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review
Authors: Fisher Cyril
Published: August 2013

Many soft tissue sarcomas have chromosomal translocations with resultant formation of new fusion genes. Among the genes that can be rearranged, the EWSR1 gene has been identified as a partner in a wide variety of clinically and pathologically diverse sarcomas as well as some non‐mesenchymal tumours. The former include Ewing sarcoma and similar (Ewing‐like) small round cell sarcomas, desmoplastic small round cell tumour, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue and clear cell sarcoma‐like tumours of the gastrointestinal tract, primary pulmonary myxoid sarcoma, extrasalivary myoepithelial tumours and sporadic examples of low‐grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma and mesothelioma. EWSR1 is a ‘promiscuous’ gene that can fuse with many different partner genes, but sometimes this results in phenotypically identical tumours. EWSR1 can, conversely, partner with the same genes in morphologically and behaviourally different neoplasms. This paper reviews the diversity of the several soft tissue tumour types that are associated with rearrangement of the EWSR1 gene.
The efficacy of chlorhexidine dentifrice or gel on plaque, clinical parameters of gingival inflammation and tooth discoloration: a systematic review
Authors: Slot DE , Berchier CE , Addy M , Van der Velden U , Van der Weijden GA
Published: August 2013

Aim

Based on the existing scientific literature, the effect of chlorhexidine (CHX) dentifrice/gel as compared to a regular or placebo dentifrice/gel is established in healthy adults on the primary outcome parameters of plaque and gingivitis scores. As secondary parameter, tooth surface discoloration was evaluated as a side effect.

Materials and methods

MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched up to July 2013 to identify eligible studies. Included were (randomized) controlled clinical trials, regarding self‐performed brushing by adults without periodontitis with a minimum duration of 4 weeks.

Results

Independent screening of 389 unique titles and abstracts resulted in 16 comparisons. Of these, nine evaluated CHX dentifrice (0.4–1.0%) and 7 CHX gel (0.2–2.0%). It was not possible to perform a meta‐analysis; therefore, a descriptive analysis was carried out. Regarding plaque score reduction, the majority of the experiments using a CHX dentifrice provided a significant positive effect. All studies assessing gingival bleeding as parameter for gingivitis observed a significant reduction in favour of CHX dentifrice over placebo dentifrice. Tooth surface discoloration was more pronounced with CHX dentifrice. The combined data concerning parameters of interest for CHX gel compared with a placebo did not show a trend towards a beneficial effect on plaque and bleeding scores.

Conclusions

Within the limitations of this analysis, it may be concluded that toothbrushing with a CHX gel does not provide conclusive evidence. Brushing with a CHX dentifrice can be effective with regard to the control of plaque and gingivitis. Tooth surface discoloration was observed as side effect, which potentially can have a negative impact on patients' compliance.
Voluntary Audit Committee Characteristics, Incentives, and Aggressive Earnings Management: Evidence from New Zealand
Authors: Sharma Vineeta D. , Kuang Chunli
Published: August 2013

This study provides initial evidence on the association between voluntary audit committee characteristics, incentives and aggressive earnings management in New Zealand. Our results suggest audit committees comprising independent (non‐executive) directors reduce (increase) the likelihood of aggressive earnings management. Financial expertise is associated with a lower likelihood of aggressive earnings management but only when the expertise is held by independent directors. Greater stock ownership by non‐executive and executive directors serving on the audit committee increases the risk of aggressive earnings management. However, stock ownership by independent directors reduces this risk. Our results show that independent directors serving on other boards are associated with a lower likelihood of aggressive earnings management. Results relating to the New Zealand audit committee regulatory guidelines show that only majority independent directors on the audit committee are associated with the likelihood of aggressive earnings management. We raise potential implications for policy makers in New Zealand.
Unravelling the Subsidiary Initiative Process: A Multilevel Approach
Authors: Strutzenberger Anna , Ambos Tina C.
Published: August 2013

Strategy‐making and entrepreneurial behaviour at the subsidiary level, in particular the phenomenon of subsidiary initiative, has received increasing research attention in recent years. In the fields of international business, strategy and entrepreneurship, several studies addressing aspects of this phenomenon have been conducted. They focused on different stages of the subsidiary initiative process, different theories and also different methodological levels. This puts subsidiary initiatives as a topic at the crossroads of several disciplines, so that theory‐building remains fragmented, and there is a lack of perspective capturing the complexity of the entire subsidiary initiative process. Based on a comprehensive literature review, this paper discusses theoretical concepts and streams of thinking that have contributed to our understanding of the subsidiary initiative process, and develops an organizing framework based on stages and levels of the subsidiary initiative process. In order to integrate theories across levels, the authors identify ‘aggregation’ theories that guide the emergence of initiatives from the individual up to the network level, and also acknowledge theories that link the micro–macro divide and may help in the development of a more holistic view of subsidiary initiatives.
Student nurses' attitudes towards professional containment methods used in psychiatric wards and perceptions of aggression
Authors: Özcan Neslihan Keser , Bilgin Hülya , Badırgalı Boyacıoğlu Nur Elçin , Kaya Fadime
Published: August 2013

The aim of this study was to determine student nurses' attitudes towards professional containment methods used in psychiatric wards and its relation to their perception of aggression.

We employed a cross‐sectional descriptive design to evaluate nurses' attitudes. Participants included 120 student nurses who were enrolled in psychiatric nursing during their fourth (final) year of education. The ‘Attitude to Containment Measures Questionnaire’ and ‘The Perception of Aggression Scale’ were used for assessments.

Student nurses exhibited positive attitudes toward ‘intermittent observation’, ‘Pro re nata Medication’ and ‘Psychiatric Intensive Care Unit’, respectively. The least approved method was ‘net bed’. The data showed a negative correlation between approval of ‘Intra‐Muscular Medication’ and ‘mechanical restraint’ with the perception that aggression was dysfunctional/unacceptable. Student nurses who believed that professional containment methods were effective also perceived aggression as less functional/acceptable. These results emphasize the importance of health care perceptions of aggression towards patients and their experience with containment measures.
Effect on pain intensity of injection sites and speed of injection associated with intramuscular penicillin
Authors: Tuğrul Emel , Khorshıd Leyla
Published: August 2013

The aim of this one‐group, quasi‐experimental study was to examine the effect of choice of injection site and injection duration on the intensity of pain associated with intramuscular penicillin injection. Injections containing the same dose of drug were administered 12 hours apart for each patient over 5 s/mL and 10 s/mL durations in the dorsogluteal and ventrogluteal sites. Sixty patients who had a medical order for intramuscular penicillin at least twice in a day and for two successive days at the same dose were included in the study. No difference in pain was perceived by participants between the two injection durations at either the dorsogluteal or the ventrogluteal site. This study showed that intramuscular penicillin can be administered to either site over 5 s/mL or 10 s/mL durations. There is a need for further research with a randomized controlled design in different settings and in a larger sample on the impact of choice of injection site and injection duration on pain intensity.