bluuebunny/crossref_metadata_2025 huggingface dataset:
HOW COMPLAINING CUSTOMERS MAKE COMPANIES LISTEN AND INFLUENCE PRODUCT DEVELOPMENT
Authors: CHRISTIANSEN JOHN K. , GASPARIN MARTA , VARNES CLAUS , AUGUSTIN INA
Published: June 2015

The analysis in this paper shows how complaining customers can make companies listen to them by spurring the mobilisation of various actors into a hybrid collective strong enough to influence companies’ product development. Customers as sources of innovation have been analysed previously in the literature, whereas the process of how complaining users mobilise support to influence companies has received less attention and is not well understood.

This study uncovers the processes that made it possible for a 17-year-old Norwegian to become pivotal in constructing a problematisation, which emerged to become so strong as to alter the Norwegian Coca-Cola Company’s earlier decision to cease production of a product in a certain size. The analysis uses constructs from actor–network theory (ANT) and shows how a single dissatisfied individual was able to become a spokesperson who, through different processes, mobilised a heterogeneous group of consumers into a loosely connected hybrid collective. The spokesperson acted on behalf of the hybrid collective and put growing pressure on a multinational company, influencing its decision making. In this case, the complaining customer did not exit, nor did he become a lead user, but rather became a hybrid customer who actively tried to mobile others in his desire for a product.

The study reports on a process analysis of the means by which the company was induced to reinstate a discontinued product. The analysis is divided into three episodes, each marking a critical phase for the collective. This opens up the way for an examination of the processes of mobilisation, interessement, enrolment and mobilisation, revealing the margins of manoeuvre and how these are negotiated and delimited in the process.
Ideal Whitehead graphs in Out(Fr) III: Achieved graphs in rank 3
Authors: Pfaff Catherine
Published: June 2015

By proving precisely which singularity index lists arise from the pair of invariant foliations for a pseudo-Anosov surface homeomorphism, Masur and Smillie [24] determined a Teichmüller flow invariant stratification of the space of quadratic differentials. In this final paper of a three-paper series, we give a first step to an [Formula: see text] analog of the Masur–Smillie theorem. Since the ideal Whitehead graphs defined by Handel and Mosher [16] give a strictly finer invariant in the analogous [Formula: see text] setting, we determine which of the 21 connected, simplicial, five-vertex graphs are ideal Whitehead graphs of fully irreducible outer automorphisms in [Formula: see text]. The rank 2 case is actually a direct consequence of the work of Masur and Smillie, as all elements of [Formula: see text] are induced by surface homeomorphisms and the index list and ideal Whitehead graph for a surface homeomorphism give precisely the same data.
Economic Impacts of FTAs on Trade in Services: Some Empirics in East Asia
Authors: Ishido Hikari
Published: June 2015

While the positive impacts of free trade agreements (FTAs) on liberalization in the services sector are widely noted, detailed quantitative analyses are rather scant. This paper takes a first step in analyzing the impact of ASEAN-related FTAs on mode 3 (commercial presence)-based trade in services. Overall, the results reveal some positive correlations between the degree of service trade liberalization in the host country and the service firms' commercial presence in that country. This points to a need to further promote service trade liberalization possibly under the auspices of the proposed Regional Comprehensive Economic Partnership (RCEP).
Distinguishing diapirs from inflated plutons: an integrated rock magnetic fabric and structural study on the Roundstone Pluton, western Ireland
Authors: McCarthy W. , Petronis M. S. , Reavy R. J. , Stevenson C. T.
Published: June 2015

Granitoid plutons account for much of the continental crust and are critical in the generation of several economic resources. Despite over a century of research, the fundamental process by which large felsic bodies intrude remains controversial. Two contrasting models persist: (1) mass ascent and subsequent cooling of magma (diapirism); (2) sheet ascent and subsequent emplacement (laccoliths). The latter hypothesis is different from the former as distinct ascent and emplacement processes must occur and be identifiable; traditional field methods rarely allow this important distinction to be made. We present field, petrographic and anisotropy of magnetic susceptibility data from the Roundstone Pluton, Connemara, western Ireland, which was previously considered a diapiric intrusion. The new data reveal anomalous subvertical magmatic lineations in the core of this circular intrusion as well as a suite of magmatic and submagmatic fabrics that parallel NNW–SSE country rock faults and coeval G2 sheets within the pluton. We deduce that these structures reflect a distinct centralized ascent process along a NNW–SSE conduit. Lateral emplacement and pluton inflation followed, ultimately forming a punched laccolith. We conclude that the combined application of the above techniques provides a unique insight into pluton architecture that removes ambiguity between contrasting diapiric and inflated pluton models.

Supplementary material:

Complete rock magnetic data tables and sample site coordinates (Irish Grid) are available at
http://www.geolsoc.org.uk/SUP18837
.
Kellwasser horizons, sea-level changes and brachiopod–coral crises during the late Frasnian in the Namur–Dinant Basin (southern Belgium): a synopsis
Authors: Mottequin Bernard , Poty Edouard
Published: June 2015

In Belgium, the Lower Kellwasser Event (LKW) corresponds to the relative sea-level maximum of the first (‘Aisemont sequence’ (AS)) of the two late Frasnian third-order sequences that are recognized here, but the Upper Kellwasser Event (UKW) may have been triggered by a series of tsunamites. The end of the middle Frasnian carbonate platform and reefs is caused by the sea-level drop and emersion of the last middle Frasnian third-order sequence (‘Lion sequence’) in the Lower
rhenana
Zone. The end of the ‘Petit-Mont’ mudmound growth during the transgressive (TST) and highstand (HST) systems tracts of the AS was caused by sea-level fall and emersion at the top of this sequence. The coral and brachiopod extinction in the Upper
rhenana
Zone, during the second late Frasnian third-order sequence (‘Lambermont sequence’ (LS)), is progressive and due to the widespread development of the dysoxic and anoxic facies, before the UKW. Only the LS TST has been identified. No sea-level fall has been recognized in relation to the UKW or near the Frasnian–Famennian boundary. The late Frasnian extinctions are more likely to be related to the decrease in the atmospheric oxygen rate and its impact on marine environments and, to complete, the UKW.
A carbonate carbon isotope record for the late Givetian (Middle Devonian) Global Taghanic Biocrisis in the type region (northern Appalachian Basin)
Authors: Zambito James J. , Joachimski Michael M. , Brett Carlton E. , Baird Gordon C. , Sarah Aboussalam Z.
Published: June 2015

During the Global Taghanic Biocrisis (
c.
385 Ma), Middle Devonian faunas worldwide underwent extinction. In the biocrisis type region, the northern Appalachian Basin, biodiversity changes occurred through three bioevents that ultimately resulted in the loss of numerous endemic taxa. Carbon isotope excursions during this biocrisis have been documented in various stratigraphic successions, but never in the type region. Herein, we reconstruct changes in δ
13
C
carb
from the biocrisis type region and compare these changes to local faunal transitions. An approximately 1.5‰ negative excursion corresponds to the first bioevent, a time of inferred global warming and replacement of most endemic taxa of the mid-palaeolatitude Appalachian Basin by invasive palaeoequatorial taxa. An approximately 2‰ positive excursion is associated with the second bioevent, recognized as a return of the endemic fauna and the loss of invasive taxa. This positive excursion occurs near the
Polygnathus ansatus–Ozarkodina semialternans
zonal boundary and is recognized elsewhere. Faunal cosmopolitanism associated with the third bioevent corresponds with an inflection in the carbon isotope record from negative to positive trending values, which agrees with a positive carbon record excursion seen elsewhere at the
semialternans
–
Schmidtognathus hermanni
zonal boundary. This new carbon isotope record provides an important reference for recognizing this biocrisis in other areas and facies.

Supplementary material:

The δ
13
C and δ
18
O dataset collected for this study is available at
http://www.geolsoc.org.uk/SUP18840
.
Investigating Perceived Emotional Correlates of Rhythmic Density in Algorithmic Music Composition
Authors: Williams Duncan , Kirke Alexis , Miranda Eduardo , Daly Ian , Hallowell James , Weaver James , Malik Asad , Roesch Etienne , Hwang Faustina , Nasuto Slawomir
Published: June 2015

Affective algorithmic composition is a growing field that combines perceptually motivated affective computing strategies with novel music generation. This article presents work toward the development of one application. The long-term goal is to develop a responsive and adaptive system for inducing affect that is both controlled and validated by biophysical measures. Literature documenting perceptual responses to music identifies a variety of musical features and possible affective correlations, but perceptual evaluations of these musical features for the purposes of inclusion in a music generation system are not readily available. A discrete feature, rhythmic density (a function of note duration in each musical bar, regardless of tempo), was selected because it was shown to be well-correlated with affective responses in existing literature. A prototype system was then designed to produce controlled degrees of variation in rhythmic density via a transformative algorithm. A two-stage perceptual evaluation of a stimulus set created by this prototype was then undertaken. First, listener responses from a pairwise scaling experiment were analyzed via Multidimensional Scaling Analysis (MDS). The statistical best-fit solution was rotated such that stimuli with the largest range of variation were placed across the horizontal plane in two dimensions. In this orientation, stimuli with deliberate variation in rhythmic density appeared farther from the source material used to generate them than from stimuli generated by random permutation. Second, the same stimulus set was then evaluated according to the order suggested in the rotated two-dimensional solution in a verbal elicitation experiment. A Verbal Protocol Analysis (VPA) found that listener perception of the stimulus set varied in at least two commonly understood emotional descriptors, which might be considered affective correlates of rhythmic density. Thus, these results further corroborate previous studies wherein musical parameters are monitored for changes in emotional expression and that some similarly parameterized control of perceived emotional content in an affective algorithmic composition system can be achieved and provide a methodology for evaluating and including further possible musical features in such a system. Some suggestions regarding the test procedure and analysis techniques are also documented here.
Creating kairos
Authors: Erickson Thomas
Published: June 2015

Social media has become globally ubiquitous, transforming how people are networked and mobilized. This forum explores research and applications of these new networked publics at individual, organizational, and societal levels.
--- Shelly Farnham, Editor
Big city, big data
Authors: Kitner Kathi R. , de Wet Thea
Published: June 2015

This forum addresses conceptual, methodological, and professional issues that arise in the UX field's continuing effort to contribute robust information about users to product planning and design.
--- David Siegel and Susan Dray, Editors
Activation of the (pro)renin receptor in the paraventricular nucleus increases sympathetic outflow in anesthetized rats
Authors: Huber Michael J. , Basu Rupsa , Cecchettini Cassie , Cuadra Adolfo E. , Chen Qing-Hui , Shan Zhiying
Published: June 2015

Previous studies have indicated that hyperactivity of brain prorenin receptors (PRR) is implicated in neurogenic hypertension. However, the role of brain PRR in regulating arterial blood pressure (ABP) is not well understood. Here, we test the hypothesis that PRR activation in the hypothalamic paraventricular nucleus (PVN) contributes to increased sympathetic nerve activity (SNA). In anaesthetized adult Sprague-Dawley (SD) rats, bilateral PVN microinjection of human prorenin (2 pmol/side) significantly increased splanchnic SNA (SSNA; 71 ± 15%, n = 7). Preinjection of either prorenin handle region peptide, the PRR binding blocker (PRRB), or tiron (2 nmol/side), the scavenger of reactive oxygen species (ROS), significantly attenuated the increase in SSNA (PRRB: 32 ± 5% vs. control, n = 6; tiron: 8 ± 10% vs. control, n = 5; P < 0.05) evoked by prorenin injection. We further investigated the effects of PRR activation on ROS production as well as downstream gene expression using cultured hypothalamus neurons from newborn SD rats. Incubation of brain neurons with human prorenin (100 nM) dramatically enhanced ROS production and induced a time-dependent increase in mRNA levels of inducible nitric oxide synthase (iNOS), NAPDH oxidase 2 subunit cybb, and FOS-like antigen 1 (fosl1), a marker for neuronal activation and a component of transcription factor activator protein-1 (AP-1). The maximum mRNA increase in these genes occurred 6 h following incubation (iNOS: 201-fold; cybb: 2 -fold; Ffosl1: 11-fold). The increases in iNOS and cybb mRNA were not attenuated by the AT1 receptor antagonist losartan but abolished by the AP-1 blocker curcumin. Our results suggest that PVN PRR activation induces sympathoexcitation possibly through stimulation of an ANG II-independent, ROS-AP-1-iNOS signaling pathway.
Effects of oral N-acetylcysteine on walking capacity, leg reactive hyperemia, and inflammatory and angiogenic mediators in patients with intermittent claudication
Authors: da Silva Natan D. , Roseguini Bruno T. , Chehuen Marcel , Fernandes Tiago , Mota Glória F. , Martin Priscila K. M. , Han Sang W. , Forjaz Cláudia L. M. , Wolosker Nelson , de Oliveira Edilamar M.
Published: June 2015

Increased oxidative stress and inflammation contribute to impaired walking capacity and endothelial dysfunction in patients with intermittent claudication (IC). The goal of the study was to determine the effects of oral treatment with the antioxidant N-acetylcysteine (NAC) on walking capacity, leg postocclusive reactive hyperemia, circulating levels of inflammatory mediators, and whole blood expression of angiogenic mediators in patients with IC. Following a double-blinded randomized crossover design, 10 patients with IC received NAC (1,800 mg/day for 4 days plus 2,700 mg before the experimental session) and placebo (PLA) before undergoing a graded treadmill exercise test. Leg postocclusive reactive hyperemia was assessed before and after the test. Blood samples were taken before and after NAC or PLA ingestions and 5 and 30 min after the exercise test for the analysis of circulating inflammatory and angiogenic markers. Although NAC increased the plasma ratio of reduced to oxidized glutathione, there were no differences between experimental sessions for walking tolerance and postocclusive reactive hyperemia. Plasma concentrations of soluble vascular cell adhesion protein-1, monocyte chemotactic protein-1, and endothelin-1 increased similarly following maximal exercise after PLA and NAC ( P < 0.001). Whole blood expression of pro-angiogenic microRNA-126 increased after maximal exercise in the PLA session, but treatment with NAC prevented this response. Similarly, exercise-induced changes in whole blood expression of VEGF, endothelial nitric oxide synthase and phosphatidylinositol 3-kinase R2 were blunted after NAC. In conclusion, oral NAC does not increase walking tolerance or leg blood flow in patients with IC. In addition, oral NAC prevents maximal exercise-induced increase in the expression of circulating microRNA-126 and other angiogenic mediators in patients with IC.
Junctional abnormalities in human airway epithelial cells expressing F508del CFTR
Authors: Molina Samuel A. , Stauffer Brandon , Moriarty Hannah K. , Kim Agnes H. , McCarty Nael A. , Koval Michael
Published: June 2015

Cystic fibrosis (CF) has a profound impact on airway physiology. Accumulating evidence suggests that intercellular junctions are impaired in CF. We examined changes to CF transmembrane conductance regulator (CFTR) function, tight junctions, and gap junctions in NuLi-1 (CFTRwt/wt) and CuFi-5 (CFTRΔF508/ΔF508) cells. Cells were studied at air-liquid interface (ALI) and compared with primary human bronchial epithelial cells. On the basis of fluorescent lectin binding, the phenotype of the NuLi-1 and CuFi-5 cells at week 8 resembled that of serous, glycoprotein-rich airway cells. After week 7, CuFi-5 cells possessed 130% of the epithelial Na+channel activity and 17% of the CFTR activity of NuLi-1 cells. In both cell types, expression levels of CFTR were comparable to those in primary airway epithelia. Transepithelial resistance of NuLi-1 and CuFi-5 cells stabilized during maturation in ALI culture, with significantly lower transepithelial resistance for CuFi-5 than NuLi-1 cells. We also found that F508del CFTR negatively affects gap junction function in the airway. NuLi-1 and CuFi-5 cells express the connexins Cx43 and Cx26. While both connexins were properly trafficked by NuLi-1 cells, Cx43 was mistrafficked by CuFi-5 cells. Cx43 trafficking was rescued in CuFi-5 cells treated with 4-phenylbutyric acid (4-PBA), as assessed by intracellular dye transfer. 4-PBA-treated CuFi-5 cells also exhibited an increase in forskolin-induced CFTR-mediated currents. The Cx43 trafficking defect was confirmed using IB3-1 cells and found to be corrected by 4-PBA treatment. These data support the use of NuLi-1 and CuFi-5 cells to examine the effects of F508del CFTR expression on tight junction and gap junction function in the context of serous human airway cells.
Normalization of Activated Partial Thromboplastin Time Correlates with Low Levels of Dabigatran in a Patient with Severe Sepsis
Authors: Højland Rikke Ebenhard , Thorup Stine Borch , Rasmussen Bodil Steen
Published: June 2015

The oral anticoagulant dabigatran etexilate can be a challenge when patients need acute surgery. Sepsis and acute renal failure exacerbate the anticoagulant effect. There is no specific reversal agent for dabigatran etexilate, but it can be removed by hemodialysis. We present a case where a patient treated with dabigatran etexilate was admitted to intensive care unit with severe sepsis and acute renal failure and in need of bilateral lower limp amputation due to ischemia. The patient had severe coagulopathy and was treated with continuous venovenous hemofiltration in attempt to remove dabigatran etexilate before surgery.
Inverse Modeling of Human Knee Joint Based on Geometry and Vision Systems for Exoskeleton Applications
Authors: Piña-Martínez Eduardo , Rodriguez-Leal Ernesto
Published: June 2015

Current trends in Robotics aim to close the gap that separates technology and humans, bringing novel robotic devices in order to improve human performance. Although robotic exoskeletons represent a breakthrough in mobility enhancement, there are design challenges related to the forces exerted to the users’ joints that result in severe injuries. This occurs due to the fact that most of the current developments consider the joints as noninvariant rotational axes. This paper proposes the use of commercial vision systems in order to perform biomimetic joint design for robotic exoskeletons. This work proposes a kinematic model based on irregular shaped cams as the joint mechanism that emulates the bone-to-bone joints in the human body. The paper follows a geometric approach for determining the location of the instantaneous center of rotation in order to design the cam contours. Furthermore, the use of a commercial vision system is proposed as the main measurement tool due to its noninvasive feature and for allowing subjects under measurement to move freely. The application of this method resulted in relevant information about the displacements of the instantaneous center of rotation at the human knee joint.
Jejunal Intussusception: A Rare Presentation of Carcinoid Tumor
Authors: Kannan Umashankkar , Rahnemai-Azar Amir A. , Patel Ashish N. , Gaduputi Vinaya , Shah Ajay K.
Published: June 2015

A 55-year-old male presented to the emergency department with sudden onset of diffuse abdominal pain for one day. Physical examination was remarkable for tenderness in the umbilical region. A CT scan of the abdomen showed intussusception involving the jejunum without any mass. The patient then underwent an exploratory laparotomy. During surgery, the distal jejunum was intussuscepted with mesenteric lymphadenopathy. Liver showed nodular deposits in both lobes of the liver. The involved small bowel segment was resected with primary anastomosis and liver was biopsied. Pathological examination showed multifocal deposits of well-differentiated carcinoids in the jejunum. The liver and mesenteric deposits were positive for metastatic carcinoid. Patient recovered well without any complications.
Neurilemmoma of Retromolar Region in the Oral Cavity
Authors: Rathore Ajit Singh , Srivastava Deepti , Narwal Nidhi , Shetty Devi Charan
Published: June 2015

Neurilemmoma also known as schwannoma is benign nerve sheath tumor rarely occurring in the oral cavity. Only 1% of all extracranial schwannomas show that intraoral occurrence with tongue is the commonest site and retromolar region is the least common site. It presents as encapsulated, slow growing, solitary, smooth-surfaced, usually asymptomatic tumor. We report a case of 70-year-old male with well-defined mass on left retromolar region which was painless and slow growing. Diagnosis is made by histological examination and immunohistochemistry analysis to confirm the neural tissue origin of the lesion. The treatment is complete surgical excision of the lesion without recurrence.
Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling
Authors: Chistiakov Dmitry A. , Sobenin Igor A. , Orekhov Alexander N. , Bobryshev Yuri V.
Published: June 2015

A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC “contractile” phenotype to the “synthetic” phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles.
Protective Effects of the MushroomLactarius deterrimusExtract on Systemic Oxidative Stress and Pancreatic Islets in Streptozotocin-Induced Diabetic Rats
Authors: Mihailović Mirjana , Arambašić Јovanović Jelena , Uskoković Aleksandra , Grdović Nevena , Dinić Svetlana , Vidović Senka , Poznanović Goran , Mujić Ibrahim , Vidaković Melita
Published: June 2015

The aim of this study was to assess thein vivoeffects of the extract of the medicinal mushroom,Lactarius deterrimus, when administered (60 mg/kg, i.p.) daily for four weeks to streptozotocin- (STZ-) induced diabetic rats. Diabetic rats treated with theL. deterrimusextract displayed several improved biochemical parameters in the circulation: reduced hyperglycemia, lower triglyceride concentration and reduced glycated hemoglobin, glycated serum protein, and advanced glycation end product (AGE) levels. This treatment also adjusted the diabetes-induced redox imbalance. Thus, higher activities of the antioxidative enzymes, superoxide dismutase, and catalase in the circulation were accompanied by increased levels of free intracellular thiols and glutathionylated proteins after treatment with theL. deterrimusextract. In addition to a systemic antioxidant effect, the administration of the extract to diabetic rats also had a positive localized effect on pancreatic islets where it decreased AGE formation, and increased the expression of chemokine CXCL12 protein that mediates the restoration ofβ-cell population through the activation of the serine/threonine-specific Akt protein kinase prosurvival pathway. As a result, the numbers of proliferating cell nuclear antigen- (PCNA-) and insulin-positiveβ-cells were increased. These results show that the ability of theL. deterrimusextract to alleviate oxidative stress and increaseβ-cell mass represents a therapeutic potential for diabetes management.
Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?
Authors: Weil Brian R. , Ozcan Cevher
Published: June 2015

Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets.
Multiplicative Isometries on ClassesMp(X)of Holomorphic Functions
Authors: Iida Yasuo , Kasuga Kazuhiro
Published: June 2015

In (Iida and Kasuga 2013), the authors described multiplicative (but not necessarily linear) isometries ofMp(X)ontoMp(X)in the case of positive integerp∈N, whereMp(X)  (p≥1)is included in the Smirnov classN∗(X). In this paper, we will generalize the result to arbitrary (not necessarily positive integer) value of the exponents0<p<∞.
Brittle Cornea Syndrome: Case Report with Novel Mutation in thePRDM5Gene and Review of the Literature
Authors: Avgitidou Georgia , Siebelmann Sebastian , Bachmann Bjoern , Kohlhase Juergen , Heindl Ludwig M. , Cursiefen Claus
Published: June 2015

A 3-year-old boy presented with acute corneal hydrops on the left eye and spontaneous corneal rupture on the right eye. A diagnosis of brittle cornea syndrome was confirmed by molecular analysis. A novel mutation, the homozygous variant c.17T>G, p.V6G, was found in the gene for PR-domain-containing protein 5 (PRDM5) in exon 1. Brittle cornea syndrome is a rare connective tissue disease with typical ocular, auditory, musculoskeletal, and cutaneous disorders. Almost all patients suffer from declined vision due to corneal scarring, thinning, and rupture. The most common ophthalmologic findings include keratoconus, progressive central corneal thinning, high myopia, irregular astigmatism, retinal detachment, and high risk for spontaneous corneal or scleral rupture. In addition to describing the case with a novel mutation here we review the current literature on brittle cornea syndrome pathogenesis, clinical findings, and therapy.
Phenotypic Spectrum of Granular Corneal Dystrophy Type II in Two Italian Families Presenting an Unusual Granular Corneal Dystrophy Type I Clinical Appearance
Authors: Mazzotta Cosimo , Traversi Claudio , Baiocchi Stefano , Barabino Stefano , Mularoni Alessandro
Published: June 2015

Clinical, instrumental, and genetic findings are reported in Italian families with Type II Granular Corneal Dystrophies (GCD2) presenting an initial unusual presentation of a Granular Corneal Dystrophy Type I (GCD1) phenotypic spectrum in female descendants. Slit-lamp examinations showed the typical phenotypic features of GCD2 in both mothers and a phenotypic appearance of GCD1 in both daughters. Despite the different phenotypic onset, the genetic diagnostic testing revealed the presence of a mutation in the TGFB-I gene, typical of GCD2 in both cases, excluding GCD1. Patients who were clinically suspected of corneal dystrophy need a genetic confirmatory testing for certain diagnosis. Genetic test may help to find the specific mutation distinguishing between different phenotypic spectra with relative diagnostic and prognostic implications. The study demonstrates that the phenotypic spectrum of genetically confirmed granular corneal dystrophies in patients may change over time. Since the R124H mutation has also been described in clinically asymptomatic individuals prior to LASIK, who then develop dramatic deposition, suggesting that this particular mutation and phenotype may be sensitive to, precipitated, or modified by central cornea trauma, a careful familial anamnesis excluding cornel dystrophies and specific preoperative genetic test are recommended prior to LASIK.
Primary Squamous Cell Carcinoma of Thyroid: A Rare Entity
Authors: Chavan Rahulkumar N. , Chikkala Bhargav , Biswas Cinjini , Biswas Somak , Sarkar Diptendra Kumar
Published: June 2015

Primary squamous cell carcinoma (PSCC) of thyroid is an extremely rare malignancy of thyroid. Herewith, we describe a case report of female patient who presented with neck swelling; FNAC misdiagnosed it as papillary carcinoma of thyroid but, after resection, biopsy revealed it to be a case of squamous cell carcinoma of thyroid. After extensive investigations no possible primary focus of squamous cell carcinoma was found elsewhere, so diagnosis of primary squamous cell carcinoma of thyroid was made. Patient underwent chemoradiation but still patient succumbed to death within a year.
Preterm Caesarean Delivery in a Parturient withCandida parapsilosisEndocarditis
Authors: Fu Jason , Retherford Lance M. , Flynn Brigid
Published: June 2015

We present the first documented case ofCandida parapsilosisinfective endocarditis in a pregnant patient. While the incidence of infective endocarditis during pregnancy is rare, the incidence ofC. parapsilosisendocarditis is even rarer. The numerous specific risks and decision making processes regarding this case are presented.
Numerical Simulations of Gravity Driven Reversible Reactive Flows in Homogeneous Porous Media
Authors: Alhumade H. , Azaiez J.
Published: June 2015

The effect of reversibility on the instability of a miscible vertical reactive flow displacement is examined. A model, where densities and/or viscosities mismatches between the reactants and the chemical product trigger instability, is adopted. The problem is governed by the continuity equation, Darcy’s law, and the convection-diffusion-reaction equations. The problem is formulated and solved numerically using a combination of the highly accurate spectral methods based on Hartley’s transform and the finite-difference technique. Nonlinear simulations were carried out for a variety of parameters to analyse the effects of the reversibility of the chemical reaction on the development of the flow under different scenarios of the frontal instability. In general, faster attenuation in the development and growth of the instability is reported as the reversibility of the chemical reaction increases. However, it was observed that reversibility is capable of triggering instability for particular choices of the densities and viscosities mismatches. In addition, the effect of the reversibility in enhancing the instability was illustrated by presenting the total relative contact area between the reactants and the product.
BMP2 Is Associated with Caries Experience in Primary Teeth
Authors: Romanos Helena Freire , Antunes Leonardo Santos , Lopes Ludiana Barbosa , Sabóia Ticiana de Medeiros , Tannure Patricia Nivoloni , Lips Andrea , Antunes Livia Azeredo A. , Abreu Fernanda Volpe de , Deeley Kathleen , Alves Gutemberg , Granjeiro José M. , Vieira Alexandre R. , Costa Marcelo C. , Küchler Erika C.
Published: June 2015

Bone morphogenetic proteins (BMPs) play an important role during the initial process of enamel development and therefore may play a role in caries susceptibility. The purpose of this study was to evaluate the association between the polymorphisms in the BMP2, BMP4 and BMP7 genes and their association with caries experience and primary enamel microhardness characteristics. DNA from buccal cells as well as clinical and demographic information from 1,731 subjects from three different data sets from Brazil were included. Polymorphisms in BMP2, BMP4 and BMP7 were analyzed by real-time polymerase chain reaction from genomic DNA. Association between caries experience, genotype, and allele distribution in both cohorts was evaluated using χ2 and logistic regression analyses. In the family-based set, the association between caries experience and alleles was tested using the transmission disequilibrium test. In the Rio de Janeiro cohort, microhardness data on 108 exfoliated primary teeth before and after demineralization and remineralization challenges was included. Associations between microhardness values and genotype and allele distribution were evaluated using χ2 and logistic regression analyses. Differences between caries experience and some risk factors were statistically significant. In the cohort from Nova Friburgo, BMP2 was associated with caries experience in primary dentition during logistic regression analysis (p = 0.023; OR = 2.58; 95% CI 1.13-5.86). There was no association between genotype and allele distribution for BMP polymorphisms and primary enamel microhardness alterations. Our result suggests that BMP2 may be involved in caries experience in primary dentition from a Nova Friburgo cohort.
Does Anticholinergic Activity Affect Neuropathology Implication of Neuroinflammation in Alzheimer's Disease
Authors: Yoshiyama Yasumasa , Kojima Ayako , Itoh Kimiko , Isose Sagiri , Koide Mizuho , Hori Koji , Arai Kimihito
Published: June 2015

One characteristic neuropathological feature of Alzheimer's disease (AD) is profound neuronal loss in the nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex. Clinically, anticholinergic activity causes a decline in cognitive function and increases the risk of dementia, thus possibly enhancing AD pathologies and neurodegeneration. Until now there has been insufficient human neuropathological data to support this conclusion. Experimental studies using a tauopathy mouse model demonstrated anticholinergics enhanced tau pathology and neurodegeneration corresponding to central anticholinergic activity. Additionally, donepezil, a cholinesterase inhibitor, ameliorated tau pathology and neurodegeneration in the same mouse model. These results indicate the balance between cholinergic and anticholinergic activities might affect neurodegeneration. Importantly, neurodegeneration observed in the mouse model seemed to correspond to the distribution of microglial activation, and it was reported that neuroinflammation plays an important role in the pathomechanism of AD, while anticholinergic activity augments inflammatory responses. Moreover, some studies indicated β-amyloid itself depletes cholinergic function similarly to anticholinergic activity. Thus, anticholinergic activity might initiate and/or accelerate AD pathology. Limited human data support the conclusion that anticholinergic activity enhances AD-related neuropathology and neurodegeneration. However, experimental data from a tauopathy mouse model indicated anticholinergic activity might enhance neurodegeneration with enhanced neuroinflammation including microglial activation.
Hypothesis of Endogenous Anticholinergic Activity in Alzheimer's Disease
Authors: Konishi Kimiko , Hori Koji , Tani Masayuki , Tomioka Hiroi , Kitajima Yuka , Akashi Norihisa , Inamoto Atsuko , Kurosawa Kenzo , Yuda Haijime , Hanashi Takahiro , Ouchi Hiromi , Hosoi Misa , Hachisu Mitsugu
Published: June 2015

In this article, we review and repropose our hypothesis of the endogenous appearance of anticholinergic activity (AA) in Alzheimer's disease (AD). First, we introduce our previous articles and speculate that, because acetylcholine (ACh) regulates both cognitive function and inflammation, downregulation of this neurotransmitter causes upregulation of the inflammatory system. AA then appears endogenously with the production of cytokines and the downregulation of ACh in AD. To support our hypothesis, we present a female AD patient whose AA was considered to occur endogenously through her AD pathology. Her serum anticholinergic activity (SAA) was positive at her first visit to our memory clinic, was negative at the 1-year and 2-year follow-up visits, and had become positive again by 3 years. We speculate that the initial positive SAA was related to her AD pathology plus mental stress, and that her SAA at 3 years was related to her AD pathology only. Consequently, we believe that 2 patterns of SAA positivity (and therefore AA) exist. One occurs when the downregulation of ACh reaches a critical level, and the other occurs with the addition of some other factor such as medication, induced illness or mental stress that causes AA to affect AD pathology. Finally, we consider the pharmacotherapy of AD based on the proposed hypothesis and conclude that cholinesterase inhibitors can be used to prevent rapid disease progression, whereas N-methyl-D-aspartate receptor antagonists should be reserved for the treatment of AD that is already in a stage of rapid progression. We also propose a staging schema for patients with AD.
A Review of the Role of Anticholinergic Activity in Lewy Body Disease and Delirium
Authors: Kitajima Yuka , Hori Koji , Konishi Kimiko , Tani Masayuki , Tomioka Hiroi , Akashi Norihisa , Hosoi Misa , Inamoto Atsuko , Hasegawa Sayaka , Kikuchi Nodoka , Takahashi Akari , Hachisu Mitsugu
Published: June 2015

We have previously proposed a hypothesis in which we argue that anticholinergic activity (AA) appears endogenously in Alzheimer's disease (AD). Acetylcholine (ACh) controls both cognitive function and inflammation. Consequently, when the downregulation of ACh reaches critical levels, the inflammatory system is upregulated and proinflammatory cytokines with AA appear. However, factors other than downregulation of ACh can produce AA; even if ACh downregulation does not reach critical levels, AA can still appear if one of these other AA-producing factors is added. These factors can include neurocognitive disorders other than AD, such as delirium and Lewy body disease (LBD). In delirium, ACh downregulation fails to reach critical levels, but AA appears due to the use of medicines, physical illnesses or mental stress (termed ‘AA inserts'). In LBD, we speculate that AA appears endogenously, even in the absence of severe cognitive dysfunction, for 2 reasons. One reason is that patterns of ACh deterioration are different in LBD from those in AD, with synergistic actions between amyloid and α-synuclein thought to cause additional or severe symptoms that accelerate the disease course. The second reason is that AA occurs through disinhibition by reduced cortisol levels that result from severe autonomic parasympathetic dysfunction in LBD.
Anticholinergic Activity and Schizophrenia
Authors: Tani Masayuki , Akashi Norihisa , Hori Koji , Konishi Kimiko , Kitajima Yuka , Tomioka Hiroi , Inamoto Atsuko , Hirata Akihito , Tomita Akisa , Koganemaru Taishi , Takahashi Akari , Hachisu Mitsugu
Published: June 2015

In this article, we review the downregulation of acetylcholinergic activity in schizophrenia and discuss the similarity and difference between Alzheimer's disease (AD) and schizophrenia in terms of acetylcholine (ACh) and anticholinergic activity (AA); then, we propose the use of cognition-enhancing therapy for schizophrenia. As ACh regulates an inflammatory system, when the cholinergic system is downregulated to a critical level, the inflammatory system is activated. We consider the possibility that AA appears endogenously in AD and accelerates AD pathology. This hypothesis can also be applied to schizophrenia. In fact, even before the onset of the disorder, in the prodromal phase of schizophrenia, cognitive dysfunction exists, and antibodies against astrocyte muscarinic-1 and muscarinic-2 receptors are present in the serum of patients with the paranoid type of schizophrenia. Then we noted that the prodromal phase in schizophrenia might correspond to the mild stage in AD and the acute phase to moderate stage concerning AA. We also think that we should enhance cognition in schizophrenia even in the prodromal phase because as mentioned above, downregulation of ACh is prominent in schizophrenia even in the prodromal phase.
High Peritoneal Glucose Exposure Is Associated with Increased Incidence of Relapsing and Recurrent Bacterial Peritonitis in Patients Undergoing Peritoneal Dialysis
Authors: Jiang Na , Zhang Zhen , Fang Wei , Qian Jiaqi , Mou Shan , Ni Zhaohui
Published: June 2015

Aim: We investigated the association of peritoneal glucose exposure and dialysis exchange number with peritonitis outcome in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods: The first episodes of bacterial peritonitis were retrospectively analyzed in 187 CAPD patients. Peritoneal glucose exposure was calculated based on PD prescription at the onset of peritonitis. Results: Patients with peritoneal glucose exposure ≤140 g/day showed a higher and complete cure rate of peritonitis (66 vs. 51.7%, p = 0.047), lower occurrence of relapsing/recurrent peritonitis (10.0 vs. 21.8%, p = 0.026) and catheter removal (14.0 vs. 26.4%, p = 0.033). Patients who exchanged more than three times every day demonstrated marginally higher catheter removal rate (24.1 vs. 13.0%, p = 0.085). Logistic analysis indicated that peritoneal glucose exposure >140 g/day was an independent predictor for relapsing/recurrent peritonitis (RR: 1.959, p = 0.042). Conclusion: High peritoneal glucose exposure is associated with increased incidence of relapsing/recurrent peritonitis in CAPD patients.
De-Endothelialized Aortic Homografts: A Promising Scaffold Material for Tissue-Engineered Heart Valves
Authors: Jing Hui , Wang Zhenzhen , Chang Qing
Published: June 2015

This study was designed to investigate the feasibility of de-endothelialized aortic homografts as a scaffold for tissue-engineered heart valves. Aortic homografts obtained from donor rabbits were treated either with collagenase to eliminate endotheliocytes or with the enzyme-detergent-nuclease method to remove all cell components. Then biomechanical properties of fresh, de-endothelialized and acellular homografts were investigated comparatively. The inflammation potential and immunogenicity were also assessed after allogenic transplantation. Expression of immune indices and inflammatory infiltration in de-endothelialized and acellular homografts were much weaker than in the controls, and no significant difference was observed between treated groups. However, heat shrinkage temperature, tensile strength and broken extension rate of acellular homografts decreased significantly compared to de-endothelialized ones. It is concluded that both de-endothelialization and thorough decellularization could reduce the immunogenicity and inflammation potential significantly, but the de-endothelialized scaffold retained better structural strength. The de-endothelialized aortic homograft might be a promising scaffold for tissue-engineered heart valves.
Complement in Lupus Nephritis: New Perspectives
Authors: Bao Lihua , Cunningham Patrick N. , Quigg Richard J.
Published: June 2015

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Summary: Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. Key Messages: SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical trials support the use of complement-targeted therapy in the treatment of SLE.