bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of MARCKS in regulated secretion from mast cells and airway goblet cells
Authors: Haddock Brookelyn J. , Zhu Yunxiang , Doyle Sean P. , Abdullah Lubna H. , Davis C. William
Published: April 2014

MARCKS (myristoylated alanine-rich C kinase substrate) is postulated to regulate the passage of secretory granules through cortical actin in the early phase of exocytosis. There are, however, three proposed mechanisms of action, all of which were derived from studies using synthetic peptides representing either the central phosphorylation site domain or the upstream, NH2-terminal domain: it tethers actin to the plasma membrane and/or to secretory granules, and/or it sequesters PIP2. Using MARCKS-null mice, we probed for a loss of function secretory phenotype in mast cells harvested from embryonic livers and maturated in vivo [embryonic hepatic-derived mast cells (eHMCs)]. Both wild-type (WT) and MARCKS-null eHMCs exhibited full exocytic responses upon FcϵRI receptor activation with DNP-BSA (2,4-dinitrophenyl-BSA), whether they were in suspension or adherent. The secretory responses of MARCKS-null eHMCs were consistently higher than those of WT cells, but the differences had sporadic statistical significance. The MARCKS-null cells exhibited faster secretory kinetics, however, achieving the plateau phase of the response with a t½∼2.5-fold faster. Hence, MARCKS appears to be a nonessential regulatory protein in mast cell exocytosis but exerts a negative modulation. Surprisingly, the MARCKS NH2-terminal peptide, MANS, which has been reported to inhibit mucin secretion from airway goblet cells (Li Y, Martin LD, Spizz G, Adler KB. J Biol Chem 276: 40982–40990, 2001), inhibited hexosaminidase secretion from WT and MARCKS-null eHMCs, leading us to reexamine its effects on mucin secretion. Results from studies using peptide inhibitors with human bronchial epithelial cells and with binding assays using purified mucins suggested that MANS inhibited the mucin binding assay, rather than the secretory response.
Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer
Authors: Tokuda Emi , Itoh Toshiki , Hasegawa Junya , Ijuin Takeshi , Takeuchi Yukiko , Irino Yasuhiro , Fukumoto Miki , Takenawa Tadaomi
Published: April 2014

Downregulation of cell–cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell–cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4)P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4)P phosphatase localized in the Golgi apparatus, resulted in decreased cell–cell adhesion and increased cell migration in weakly invasive cells. In contrast, silencing phosphatidylinositol 4-kinase IIIβ, which generates PI(4)P in the Golgi apparatus, increased cell–cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI(4)P effector, Golgi phosphoprotein 3, was found to be involved in the generation of these phenotypes in a manner that depends on its PI(4)P-binding ability. Our results provide a new model for breast cancer cell progression in which progression is controlled by PI(4)P levels in the Golgi apparatus. Cancer Res; 74(11); 3054–66. ©2014 AACR.
Strengths, Weaknesses, and Opportunities of Diagnostic Breathomics in Pleural Mesothelioma—A Hypothesis
Authors: Lamote Kevin , Nackaerts Kristiaan , van Meerbeeck Jan P.
Published: April 2014

Past and present asbestos use will reflect in increasing numbers of mesothelioma cases in the next decades, diagnosed at a late stage and with a dismal prognosis. This stresses the need for early detection tools, which could improve patients' survival. Recently, breath analysis as a noninvasive and fast diagnostic tool has found its way into biomedical research. High-throughput breathomics uses spectrometric, chromatographic, and sensor techniques to diagnose asbestos-related pulmonary diseases based upon volatile organic compounds (VOC) in breath. This article reviews the state-of-the-art available breath analyzing techniques and provides the insight in the current use of VOCs as early diagnostic or prognostic biomarkers of mesothelioma to stimulate further research in this field. Cancer Epidemiol Biomarkers Prev; 23(6); 898–908. ©2014 AACR.
Cancer Screening and Genetics: A Tale of Two Paradigms
Authors: Hamilton Jada G. , Edwards Heather M. , Khoury Muin J. , Taplin Stephen H.
Published: April 2014

The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to disease. Genetic risk information can have varying implications for the health and well-being of patients and their relatives, and has raised important questions about the evaluation and value of risk information. This article explores the paradigms that are being applied to the evaluation of conventional cancer screening tests and emerging genetic and genomic tests of cancer susceptibility, and how these perspectives are shifting and evolving in response to advances in our ability to detect cancer risks. We consider several challenges germane to the evaluation of both categories of tests, including defining benefits and harms in terms of personal and clinical utility, addressing healthcare consumers' information preferences, and managing scientific uncertainty. We encourage research and dialogue aimed at developing a better understanding of the value of all risk information, nongenetic and genetic, to people's lives. Cancer Epidemiol Biomarkers Prev; 23(6); 909–16. ©2014 AACR.
UPARANT: A Urokinase Receptor–Derived Peptide Inhibitor of VEGF-Driven Angiogenesis with Enhanced Stability and In Vitro and In Vivo Potency
Authors: Carriero Maria Vincenza , Bifulco Katia , Minopoli Michele , Lista Liliana , Maglio Ornella , Mele Luigi , Di Carluccio Gioconda , De Rosa Mario , Pavone Vincenzo
Published: April 2014

This work is based on previous evidence showing that chemotactic sequence of the urokinase receptor (uPAR88-92) drives angiogenesis in vitro and in vivo in a protease-independent manner, and that the peptide Ac-Arg-Glu-Arg-Phe-NH2 (RERF) prevents both uPAR88–92- and VEGF-induced angiogenesis. New N-acetylated and C-amidated peptide analogues containing α-methyl α-amino acids were designed and synthesized to optimize the biochemical properties for therapeutic applications. Among these, Ac-L-Arg-Aib-L-Arg-D-Cα(Me)Phe-NH2, named UPARANT, adopts in solution a turned conformation similar to that found for RERF, is stable to sterilization in 3 mg/mL sealed vials in autoclave for 20 minutes at 120°C, is stable in blood, and displays a long-time resistance to enzymatic proteolysis. UPARANT competes with N-formyl-Met-Leu-Phe (fMLF) for binding to the formyl-peptide receptor, inhibits VEGF-directed endothelial cell migration, and prevents cytoskeletal organization and αvβ3 activation in endothelial cells exposed to VEGF. In vitro, UPARANT inhibits VEGF-dependent tube formation of endothelial cells at a 100× lower concentration than RERF. In vivo, UPARANT reduces to the basal level VEGF-dependent capillary sprouts originating from the host vessels that invaded Matrigel sponges implanted in mice, and completely prevents neovascularization induced by subcorneal implantation of pellets containing VEGF in rabbits. Both excellent stability and potency position UPARANT as a promising new therapeutic agent for the control of diseases fueled by excessive angiogenesis, such as cancer and inflammation. Mol Cancer Ther; 13(5); 1092–104. ©2014 AACR.
Development of an Active Site Peptide Analog of α-Fetoprotein That Prevents Breast Cancer
Authors: Jacobson Herbert I. , Andersen Thomas T. , Bennett James A.
Published: April 2014

Epidemiologic studies associate elevated maternal serum levels of α-fetoprotein (AFP) with reduced breast cancer risk for parous women. Laboratory studies demonstrate direct anti-breast cancer activity of AFP. Here, we review the development of a small cyclic peptide that is an active site analog of AFP, referred to as AFPep, which is composed exclusively of amino acids, is orally active, has no discernable toxicity, and is effective for the treatment and prevention of breast cancer in animal models. Cancer Prev Res; 7(6); 565–73. ©2014 AACR.
Truncating Plakophilin-2 Mutations in Arrhythmogenic Cardiomyopathy Are Associated With Protein Haploinsufficiency in Both Myocardium and Epidermis
Authors: Rasmussen Torsten B. , Nissen Peter H. , Palmfeldt Johan , Gehmlich Katja , Dalager Søren , Jensen Uffe B. , Kim Won Y. , Heickendorff Lene , Mølgaard Henning , Jensen Henrik K. , Baandrup Ulrik T. , Bross Peter , Mogensen Jens
Published: April 2014

Background—

Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure, and sudden death. The disease is most often caused by mutations in the desmosomal gene for plakophilin-2 (
PKP2
), which is expressed in both myocardial and epidermal tissue. This study aimed to investigate protein expression in myocardial tissue of patients with AC carrying
PKP2
mutations and elucidate whether keratinocytes of the same individuals exhibited a similar pattern of protein expression.

Methods and Results—

Direct sequencing of 5 AC genes in 71 unrelated patients with AC identified 10 different
PKP2
mutations in 12 index patients. One patient, heterozygous for a
PKP2
nonsense mutation, developed severe heart failure and underwent cardiac transplantation. Western blotting and immunohistochemistry of the explanted heart showed a significant decrease in PKP2 protein expression without detectable amounts of truncated PKP2 protein. Cultured keratinocytes of the patient showed a similar reduction in PKP2 protein expression. Nine additional
PKP2
mutations were investigated in both cultured keratinocytes and endomyocardial biopsies from affected individuals. It was evident that
PKP2
mutations introducing a premature termination codon in the reading frame were associated with PKP2 transcript and protein levels reduced to ≈50%, whereas a missense variant did not seem to affect the amount of PKP2 protein.

Conclusions—

The results of this study showed that truncating
PKP2
mutations in AC are associated with low expression of the mutant allele and that the myocardial protein expression of PKP2 is mirrored in keratinocytes. These findings indicate that
PKP2
haploinsufficiency contributes to pathogenesis in AC.
Transplantation-Free Survival and Interventions at 3 Years in the Single Ventricle Reconstruction Trial
Authors: Newburger Jane W. , Sleeper Lynn A. , Frommelt Peter C. , Pearson Gail D. , Mahle William T. , Chen Shan , Dunbar-Masterson Carolyn , Mital Seema , Williams Ismee A. , Ghanayem Nancy S. , Goldberg Caren S. , Jacobs Jeffrey P. , Krawczeski Catherine D. , Lewis Alan B. , Pasquali Sara K. , Pizarro Christian , Gruber Peter J. , Atz Andrew M. , Khaikin Svetlana , Gaynor J. William , Ohye Richard G.
Published: April 2014

Background—

In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle–to–pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups.

Methods and Results—

Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%;
P
=0.15) or with all available follow-up of 4.8±1.1 years (log-rank
P
=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7
±
5.1% versus 44.7
±
6.0%;
P
=0.007), and right ventricular ejection fraction deteriorated in RVPAS (
P
=0.004) but not MBTS (
P
=0.40) subjects (pre-Fontan minus 14-month mean, −3.25±8.24% versus 0.99±8.80%;
P
=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (
P
=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45–0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07–4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (
P
<0.001) with an increasing HR over time (
P
=0.005): <5 months, 1.14 (95% confidence interval, 0.81–1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02–3.69); and >1 year, 2.48 (95% confidence interval, 1.28–4.80).

Conclusions—

By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00115934.
Surveillance and System Avoidance
Authors: Brayne Sarah
Published: April 2014

The degree and scope of criminal justice surveillance increased dramatically in the United States over the past four decades. Recent qualitative research suggests the rise in surveillance may be met with a concomitant increase in efforts to evade it. To date, however, there has been no quantitative empirical test of this theory. In this article, I introduce the concept of “system avoidance,” whereby individuals who have had contact with the criminal justice system avoid surveilling institutions that keep formal records. Using data from Add Health ( n = 15,170) and the NLSY97 ( n = 8,894), I find that individuals who have been stopped by police, arrested, convicted, or incarcerated are less likely to interact with surveilling institutions, including medical, financial, labor market, and educational institutions, than their counterparts who have not had criminal justice contact. By contrast, individuals with criminal justice contact are no less likely to participate in civic or religious institutions. Because criminal justice contact is disproportionately distributed, this study suggests system avoidance is a potential mechanism through which the criminal justice system contributes to social stratification: it severs an already marginalized subpopulation from institutions that are pivotal to desistance from crime and their own integration into broader society.
Intraoperatively Diagnosed Cerebellopontine Angle Facial Nerve Schwannoma
Authors: Bacciu Andrea , Medina Marimar , Ben Ammar Mehdi , D’Orazio Flavia , Di Lella Filippo , Russo Alessandra , Magnan Jacques , Sanna Mario
Published: April 2014

Objective:

This study aimed to report our experience in the management of patients with intraoperatively diagnosed intracranial facial nerve schwannomas (FNSs) and propose a decision-making strategy.

Methods:

Twenty-three patients with FNS of the internal auditory canal and/or cerebellopontine angle operated on between 1992 and 2012 were identified.

Results:

Preoperatively, all cases have been radiographically diagnosed as vestibular schwannomas. Operative procedures consisted of total tumor resection with grafting in 43.4% of patients, near-total resection leaving behind the tumor capsule overlying the facial nerve in 21.7%, total tumor resection with preservation of anatomic continuity of the facial nerve in 13%, and subtotal resection in 4.3%. Four patients (17.4%) underwent bony decompression with no tumor removal.

Conclusion:

Management of FNS diagnosed at surgery represents a significant clinical challenge. We considered total tumor resection with grafting when patients presented with preoperative facial nerve palsy (≥ grade III). Both subtotal and near-total tumor removal can be performed in patients with preoperative good facial function and/or large tumors with brainstem compression. Patients with small tumors who were selected for hearing preservation surgery can be considered for bony decompression. Fascicle preservation surgery may be an option when a clear cleavage plane between the tumor and the facial nerve is found.
Harmonic Scalpel Assisted Superficial Parotidectomy
Authors: Muhanna Nidal , Peleg Uri , Schwartz Yehuda , Shaul Hanan , Perez Ronen , Sichel Jean-Yves
Published: April 2014

Objective:

The Harmonic Scalpel (HS) has been recently widely used to perform a variety of surgical procedures. We reviewed our experience with the use of HS in superficial parotidectomy to determine the safety and efficacy of this procedure, with regard to operative time, postoperative facial nerve function, and drainage output.

Study Design:

Nonrandomized retrospective review.

Materials and Methods:

The medical records of all patients who underwent superficial parotidectomy for benign pathology at Shaare Zedek Medical Center from January 2006 to July 2009 were retrospectively reviewed. Patients with prior facial nerve weakness or prior parotid surgery or who had undergone concurrent neck dissection or total parotidectomy were excluded.

Results:

Fifty-eight patients were reviewed; 26 patients underwent HS parotidectomy and 32 patients underwent conventional (cold knife) parotidectomy (control group). Harmonic Scalpel assisted parotidectomy was associated with significantly decreased length of surgery from 163.12 ± 21.8 minutes for controls to 137.3 ± 18.6 minutes in the HS assisted group ( P < .05). The incidence of temporary postoperative facial nerve paresis was significantly reduced from 43% in the controls to 23% in the HS group ( P < .05). No permanent facial nerve paralysis was reported. There were differences in the overall postoperative drain output between the HS and control groups, 68 ± 22.3 mL and 73.5 ± 38.2 mL, respectively, but these differences did not achieve significance.

Conclusion:

This study shows that HS assisted superficial parotidectomy for benign pathology is a safe technique and associated with reduced surgical time and incidence of temporary postoperative facial nerve paresis compared with conventional techniques.
Preventing Cuff Rupture During Tracheostomy
Authors: Sood Amit , Taheri M. Reza , Joshi Arjun S.
Published: April 2014

Objective:

The objective of our study is to describe the technique of distal endotracheal tube (ETT) positioning for avoiding cuff rupture and validate the technique in a virtual tracheostomy model.

Methods:

A prospective nonrandomized case series of 129 patients who had undergone tracheostomy using the senior author’s technique were evaluated. Primary outcome was ETT cuff rupture. One hundred normal patient computed tomography (CT) scans were used to generate a virtual tracheostomy model, and the probability of cuff rupture, among other values, was obtained.

Results:

One hundred twenty-three of 129 patients underwent tracheostomy without cuff rupture when the distal tip of the ETT was placed just proximal to the carina. After analysis of 100 3-dimensional CT scans, the average distance from the tracheotomy to the superior aspect of the cuff was 54.6 mm in men and 39.87 mm in women when a 6.5-size ETT was used, and 44.8 mm in men and 30.07 mm in women when a 7.5-size ETT was used. Virtual tracheotomy between the second and third tracheal rings resulted in no probability of inadvertent ETT cuff rupture.

Conclusion:

Distal ETT positioning during tracheostomy should be considered for avoiding inadvertent ETT cuff rupture.
Impedance Probe Testing Prior to Pediatric Airway Reconstruction
Authors: Hart Catherine K. , de Alarcon Alessandro , Tabangin Meredith E. , Hamilton Steven , Rutter Michael J. , Pentiuk Scott P. , Garza Jose M.
Published: April 2014

Objective:

This study aimed to determine if preoperative impedance testing changed management and if testing was associated with surgical outcome in patients undergoing airway reconstruction.

Methods:

Retrospective review of patients who had impedance testing prior to airway reconstruction at a tertiary pediatric hospital from January 2010 to September 2011. Charts were reviewed for demographics, medical/surgical history, impedance testing, and surgical outcomes.

Results:

Fifty-seven patients were included. Forty-seven (82%) were premature. Forty-seven (82%) had a primary diagnosis of subglottic stenosis. Twenty-six (45%) had prior airway surgery. Thirty-six (63%) had gastroesophageal reflux and 21 (36%) had undergone fundoplication. Patients without fundoplication had a median 46 total reflux, 7 proximal, and 14.5 acidic events compared to a median 5 total reflux, 0 proximal, and 0 acidic events in patients with fundoplication. Impedance testing changed management in 22% (8/36) of nonfundoplication patients and 9.5% (2/21) of fundoplication patients. In unadjusted analysis, fewer fundoplication patients had successful surgery compared to those without (33% vs 67%, P = .01). Prematurity, age at surgery, and previous airway surgery were also important predictors of surgical success.

Conclusion:

Fewer patients than anticipated had a change in management. Impedance testing was unlikely to change management in fundoplication patients. Patients with fundoplication were less likely to have a successful outcome, suggesting that factors other than reflux influence airway reconstruction outcomes.
Oxidative status and the severity of clinical symptoms in patients with post-traumatic stress disorder
Authors: Borovac Štefanović Leda , Kalinić Dubravka , Mimica Ninoslav , Beer Ljubić Blanka , Aladrović Jasna , Mandelsamen Perica Marina , Ćurić Maja , Grošić Petra Folnegović , Delaš Ivančica
Published: April 2014

Background

The aim of this study was to measure the parameters of oxidative stress in the blood of patients with post-traumatic stress disorder.

Methods

The study included 80 male war veterans who participated actively in the Homeland war in Croatia. Volunteers were divided into two groups: 50 veterans diagnosed with post-traumatic stress disorder and 30 without diagnosis. The self-assessment Hospital Anxiety and Depression Scale and the Beck Depression Inventory were used to detect the severity of depression and anxiety in the post-traumatic stress disorder patients. Catalytic concentrations of superoxide dismutase and glutathione peroxidase in erythrocytes and the concentration of malondialdehyde in serum were measured spectrophotometrically.

Results

Although the catalytic concentrations of erythrocyte superoxide dismutase and erythrocyte glutathione peroxidase were within the reference range for both groups, the values obtained for the post-traumatic stress disorder group were significantly lower ( P < 0.001). For serum malondialdehyde concentrations, no statistically significant differences between the groups were found.

Conclusions

Lower catalytic concentrations of erythrocyte superoxide dismutase and erythrocyte glutathione peroxidase in patients with post-traumatic stress disorder may indicate a weaker response to oxidative stress due to impaired enzyme activity and/or decreased synthesis. Conversely, no significant changes in serum malondialdehyde concentrations suggest a compensated balance and adaptive response to (oxidative) stress.
The Code of Silence in Schools
Authors: Slocum Lee Ann , Esbensen Finn-Aage , Taylor Terrance J.
Published: April 2014

Socio-ecological models of victimization reporting incorporate normative constraints and instrumental considerations at the individual and contextual levels. Drawing on this model, we explore factors related to students’ willingness to report problem behaviors that they might observe in school. Data obtained from student and teacher/administrator surveys and administrative data are used to explore these relationships. We find that individual-level factors are the primary determinants of reporting attitudes, but school context is also important. Students are more willing to report misbehavior in schools with democratic authority structures and consistent enforcement of school rules. Attitudes toward reporting are less favorable when the school culture is supportive of a street code, and the effect of street code culture is fully explained by students’ personal norms and experiences. We also find evidence that personal adherence to a street code moderates the effect of school context on reporting attitudes. Implications for theory and practice are discussed.
Ophthalmomyiasis externa: three cases caused by Oestrus ovis larvae in Turkey
Authors: Çalışkan Sinan , Ugurbaş Sılay Cantürk , Sağdık Murat
Published: April 2014

Ocular involvement of parasitic infections includes external, internal and orbital ophthalmomyiasis. Oestrus ovis (sheep botfly) is the most common cause of ophthalmomyiasis externa. Living in warm climates, particularly in agricultural districts, is a risk factor. Although external ophthalmomyiasis can be treated by removal of the infecting larva(e) and topical drug treatment, the risk remains of its presence leading to further contamination for other people. We describe three cases of external ophthalmomyiasis due to infestation with the first instar larvae of O. ovis An awareness of larval conjunctivitis in endemic areas may avoid misdiagnosis and allow immediate management to prevent complications.
Presence of accessory penis, colonic duplication and several other congenital anomalies in a child: a very rare association
Authors: Chatterjee Sayan , Mondal Prabodh Chandra , Pandey Shashi Bhushan , Achar Arun
Published: April 2014

An accessory penis is a very rare anomaly. Only five cases have been reported thus far to our knowledge. We present the case of a child aged 2 years and 10 months who had a penis-like structure (containing phallus and glans) attached to the right buttock. Associated anomalies were a non-communicating type of colonic duplication, a paramedian stenosed anal opening, a horse-shoe kidney, posterior urethral valves, scoliosis of the lumbo-sacral spine, polydactyly and equino-varus deformity of the right foot. As far as we can tell, this is the first report of an accessory penis associated with colonic duplication and other congenital anomalies.
Community College Student Success
Authors: Martin Kimberly , Galentino Richard , Townsend Lori
Published: April 2014

Nationwide, low percentages of community college students graduate. Although community colleges’ higher percentages of low income, academically underprepared, non-traditional, and minority students are often cited as the reason for low graduation rates, this study sought to examine common characteristics of community college students who do graduate. The qualitative study included interviews of community college graduates from a large, public community college in the Southeastern United States, as well as interviews of faculty and staff members at the institution. The students in this study were found to have the following characteristics in common: clear goals, strong motivation and a drive to succeed, ability to manage external demands, and self-empowerment.
The Supportive Factors of Firms’ Collusive Behavior: Empirical Evidence from Cartels in the European Union
Authors: Bertrand Olivier , Lumineau Fabrice , Fedorova Evgenia
Published: April 2014

While cartels can be highly detrimental to society and create important economic and social costs for different stakeholders, the literature on organization studies has focused very little on cartels to date. In particular, we still do not know much about firms’ reasons for taking part in cartels. In this study, we build on the rational choice perspective in organizational misconduct to investigate the conditions supporting firms’ collusive behavior. We organize our theoretical arguments around the factors related to motivation and opportunity. Using a sample of cartels in the European Union, our empirical analysis gives evidence for our main arguments: the propensity to participate to a cartel is supported not only by the characteristics of the firm, but also by internal factors interacting with the attributes of the environment in which the firm is embedded. Implications for firms and policy makers are discussed.
Registering ‘the Ethical’ in Organization Theory Formation: Towards the Disclosure of an ‘Invisible Force’
Authors: Ezzamel Mahmoud , Willmott Hugh
Published: April 2014

Theory building is conditioned by three registers – the ontological (reality), the epistemological (knowledge) and the ethical (values). The significance of the first two is widely acknowledged. But the third register tends to be overlooked, especially where a positive/normative dichotomy is assumed. Post-positivist thinking problematizes this dichotomy but leaves the ethical register unthematized. The paper addresses this neglect and illustrates the role of the ethical register in processes of theory formation. Attentiveness to the ethical register is seen to invite radical reflection on a dominant, anthropocentric value-orientation, and thereby problematize the institutionalized estrangement of researchers from the ‘objects’ of their analysis and the abstraction of organizations from their embeddedness in the biosphere.
Inhaled Multiwalled Carbon Nanotubes Modulate the Immune Response of Trimellitic Anhydride–induced Chemical Respiratory Allergy in Brown Norway Rats
Authors: Staal Yvonne C. M. , van Triel Jos J. , Maarschalkerweerd Thérèse V. P. , Arts Josje H. E. , Duistermaat Evert , Muijser Hans , van de Sandt Johannes J. M. , Kuper C. Frieke
Published: April 2014

The interaction between exposure to nanomaterials and existing inflammatory conditions has not been fully established. Multiwalled carbon nanotubes (MWCNT; Nanocyl NC 7000 CAS no. 7782-42-5; count median diameter in atmosphere 61 ± 5 nm) were tested by inhalation in high Immunoglobulin E (IgE)-responding Brown Norway (BN) rats with trimellitic anhydride (TMA)-induced respiratory allergy. The rats were exposed 2 days/week over a 3.5-week period to a low (11 mg/m3) or a high (22 mg/m3) concentration of MWCNT. Nonallergic animals exposed to MWCNT and unexposed allergic and nonallergic rats served as controls. At the end of the exposure period, the allergic animals were rechallenged with TMA. Histopathological examination of the respiratory tract showed agglomerated/aggregated MWCNT in the lungs and in the lung-draining lymph nodes. Frustrated phagocytosis was observed as incomplete uptake of MWCNT by the alveolar macrophages and clustering of cells around MWCNT. Large MWCNT agglomerates/aggregates were found in granulomas in the allergic rats, suggesting decreased macrophage clearance in allergic rats. In allergic rats, MWCNT exposure decreased serum IgE levels and the number of lymphocytes in bronchoalveolar lavage. In conclusion, MWCNT did not aggravate the acute allergic reaction but modulated the allergy-associated immune response.
The Role of eNOS Phosphorylation in Causing Drug-induced Vascular Injury
Authors: Tobin Grainne A. McMahon , Zhang Jun , Goodwin David , Stewart Sharron , Xu Lin , Knapton Alan , González Carlos , Bancos Simona , Zhang Leshuai , Lawton Michael P. , Enerson Bradley E. , Weaver James L.
Published: April 2014

Previously we found that regulation of eNOS is an important part of the pathogenic process of Drug-induced vascular injury (DIVI) for PDE4i. The aims of the current study were to examine the phosphorylation of eNOS in mesentery versus aorta at known regulatory sites across DIVI-inducing drug classes and to compare changes across species. We found that phosphorylation at S615 in rats was elevated 35-fold 2 hr after the last dose of CI-1044 in mesentery versus 3-fold in aorta. Immunoprecipitation studies revealed that many of the upstream regulators of eNOS activation were associated with eNOS in 1 or more signalosome complexes. Next rats were treated with drugs from 4 other classes known to cause DIVI. Each drug was given alone and in combination with SIN-1 (NO donor) or L-NAME (eNOS inhibitor), and the level of eNOS phosphorylation in mesentery and aorta tissue was correlated with the extent of vascular injury and measured serum nitrite. Drugs or combinations produced altered serum nitrite levels as well as vascular injury score in the mesentery. The results suggested that phosphorylation of S615 may be associated with DIVI activity. Studies with the species-specific A2A adenosine agonist CI-947 in rats versus primates showed a similar pattern.
Vaginal Fold Histology Reduces the Variability Introduced by Vaginal Exfoliative Cytology in the Classification of Mouse Estrous Cycle Stages
Authors: Gal Arnon , Lin Po-Ching , Barger Anne M. , MacNeill Amy L. , Ko CheMyong
Published: April 2014

Vaginal exfoliative cytology is commonly used in biomedical and toxicological research to classify the stages of the rodent estrous cycle. However, mouse vaginal exfoliative cytology is commonly used as a stand-alone tool and has not been evaluated in reference to vaginal histology and serum sex hormone levels. In this study, the direct and Giemsa-stained methods of vaginal exfoliative cytology were compared in reference to vaginal fold histology and serum sex hormone levels. Both methods predicted the estrous stages similarly with mean discordance rates of 55%, 77%, 46%, and 31%, for diestrus, proestrus, estrus, and metestrus, respectively. From these results, we conclude that vaginal exfoliative cytology may be used as a general guide to determine the desired estrous stage end point and that a definitive confirmation of the estrous stage should be obtained from evaluation of vaginal fold histology. Confirmation of the stage of the estrous cycle by vaginal fold histology will decrease the variability otherwise introduced by misclassification of estrous cycle stages with vaginal exfoliative cytology.
Macrophage Infiltrate Is Elevated in CRSwNP Sinonasal Tissue Regardless of Atopic Status
Authors: Banks Caroline A. , Schlosser Rodney J. , Wang Eric W. , Casey Sarah E. , Mulligan Ryan M. , Mulligan Jennifer K.
Published: April 2014

Objective

Macrophages are major producers of inflammatory cytokines; however, their role in chronic rhinosinusitis (CRS) has not been clearly defined. The aim of this study was to quantify macrophages in sinus tissue of patients with various subtypes of CRS and determine the impact of atopic status on macrophage infiltrate.

Study Design

Prospective immunohistochemical study of human sinonasal tissue.

Setting

Academic medical center.

Subjects and Methods

Human sinonasal tissue was taken from patients with CRS with nasal polyposis (CRSwNP, n = 8), CRS without nasal polyposis (CRSsNP, n = 8), and controls (n = 8) undergoing surgery for CSF leak repair or endoscopic excision of non‐secreting pituitary tumor. Samples were immunohistochemically stained for macrophage/monocyte markers Mac387 and CD68.

Results

CRSwNP patients had significantly increased numbers of Mac387 and CD68 cells compared to control patients (P <. 05) or CRSsNP patients (P <. 01). CRSsNP had significantly increased number of cells staining for CD68 compared to controls (P <. 05). The increased presence of macrophages measured by either marker in CRSwNP was independent of atopic status.

Conclusion

Macrophages are increased in CSRwNP patients regardless of atopic status and may contribute to the immunopathology of CRS.
Risk Factors for Preoperative and Postoperative Hearing Loss in Children Undergoing Pressure Equalization Tube Placement
Authors: Sidell Douglas , Hunter Lisa L. , Lin Li , Arjmand Ellis
Published: April 2014

Objective

Pressure equalization tube (PET) placement is the most common surgical procedure performed during childhood. Current guidelines recommend more prompt management of children with otitis media with effusion who are at greater risk for speech‐language and developmental problems. This study was designed to examine risk factors for continued post‐PET hearing loss in a large pediatric clinical sample.

Study Design

Retrospective analysis using the electronic medical record.

Setting

Tertiary care children's hospital.

Subjects

Pediatric patients undergoing PET placement between January 2009 and October 2012 who had audiometric tests.

Methods

Demographics, patient diagnoses, and hearing loss information were extracted. Multivariate binary logistic regression models were used to identify associations between patient‐specific characteristics and the presence of hearing loss.

Results

In total, 3949 children with 4598 audiology visits were included (2357 males and 1592 females; mean age, 3.3 years), and 1272 preoperative and 3329 postoperative audiograms were performed. Using multivariate modeling, the only variable significantly associated with preoperative hearing loss was low tympanometric static acoustic admittance. Postoperative hearing loss was positively associated with patient age, preoperative hearing loss, lower tympanometric equivalent canal volumes, and Down syndrome. Other factors, including cranial/facial anomalies, low birth weight or prematurity, allergies, and asthma, were not determined to be risk factors for hearing loss.

Conclusion

Our results support hearing testing to identify candidates for PET surgery and to determine treatment effectiveness after surgery, since hearing loss cannot be predicted on the basis of risk or demographic factors. These data have important preoperative counseling and postoperative management implications.
Surgical Techniques for Zenker's Diverticulum: A Comparative Analysis
Authors: Leibowitz Jason M. , Fundakowski Christopher E. , Abouyared Marianne , Rivera Andrew , Rudman Jason , Lo Ka‐Ming , Weed Donald , Civantos Francisco
Published: April 2014

Objective

To compare the different modalities for treatment of Zenker's diverticulum and the associated clinical outcomes.

Study Design

Case series with chart review.

Setting

Tertiary care hospital.

Subjects and Methods

Between 1995 and 2011, 164 patients underwent surgery for Zenker's diverticulum (stapler, n = 69; laser, n = 68; open, n = 27). Patient sociodemographics, medical comorbidities, pre‐ and postoperative subjective dysphagia and regurgitation score, complications, length of stay, time to oral intake, and recurrence were reviewed for each surgical modality.

Results

No statistically significant difference in diverticulum prevalence was associated with age, gender, or treatment group. Mean length of hospital stay was not significantly different between the 3 groups (P =. 14). A significant difference in time to oral intake was observed in the laser group compared with the other 2 groups (P =. 012). No significant difference in recurrence (P =. 21) or complication (P =. 12) rates was identified between the 3 groups. Although all 3 groups demonstrated a significant decrease between preoperative and postoperative dysphagia and regurgitation scores, the degree of improvement was not significant when the 3 groups were compared.

Conclusion

There is no single “best” approach to Zenker's diverticulum. The open, laser, and stapler methods are equally effective and have similar complication rates.
Resident Research Experience and Career Path Association: A National Survey of Recent Otolaryngology Graduates
Authors: Zahtz Gerald , Vambutas Andrea , Hussey Heather M. , Rosen Lisa
Published: April 2014

Objective

To determine whether the research rotation experience affects the career path of otolaryngology residents.

Study Design/Setting

Two web‐based surveys were disseminated by the AAO‐HNS; one to current and former resident trainees and the other to current residency program directors.

Subjects and Methods

A web‐based survey was disseminated to all AAO‐HNS members classified as otolaryngology residents or residency graduates within the last 6 years, regarding their research rotation and its potential influence on their career path. A second web‐based survey was delivered simultaneously to program directors to evaluate their perception of the need for research in a training program and their role in the rotation. Chi‐square tests for independence as well as multivariate analyses were conducted to determine whether aspects of the resident research rotation related to career path.

Results

The resident survey was completed by 350 respondents (25% response rate), and 39 program directors completed the second survey (37% response rate). Multiple factors were examined, including federal funding of faculty, mentorship, publications prior to residency, success of research project measured by publication or grant submission, and type of research. Multivariate analyses revealed that factors most predictive of academic career path were intellectual satisfaction and presence of a T32 training grant within the program (P <. 05).

Conclusion

The composition and quality of the residency research rotation vary across institutions. Factors that enhance stronger intellectual satisfaction and the presence of T32 grant, which demonstrates an institution's commitment to research training, may promote pursuit of a career in academia versus private practice.
Discrepancy between Objective and Subjective Outcomes after Adenotonsillectomy in Children with Obstructive Sleep Apnea Syndrome
Authors: Kang Kun‐Tai , Weng Wen‐Chin , Lee Chia‐Hsuan , Lee Pei‐Lin , Hsu Wei‐Chung
Published: April 2014

Objective

Adenotonsillectomy (T&A) is the first line therapy for pediatric obstructive sleep apnea (OSA); however, inconsistency between objective and subjective outcomes perplexes physicians. This study investigates changes of objective and subjective outcomes in children with OSA after T&A, in particular, to elucidate correlations and discrepancies between these 2 measures.

Study Design

Case series with record review.

Setting

Tertiary referral medical center.

Subjects and Methods

Symptomatic children with polysomnographic diagnosis of OSA (apnea‐hypopnea index [AHI] > 1) were included. All children underwent T&A to treat OSA, along with completely objective (polysomnography) and subjective (Obstructive Sleep Apnea 18‐Item Quality‐of‐Life Questionnaire [OSA‐18]) measures before and 3 months after surgery.

Results

One hundred nineteen children were included (mean age, 6.9 ± 3.3 years; 76% boys). Adenotonsillectomy significantly reduced AHI from 15.4 ± 21.2 per hour to 1.6 ± 2.5 per hour (P <. 001). The OSA‐18 scores were significantly improved after surgery (P <. 001). A weak but statistically significant positive correlation was found between AHI and OSA‐18 scores preoperatively (ρ = 0.22, P =. 016) but not postoperatively (ρ = 0.04, P =. 677). Among those cases with residual OSA after surgery, only 6% (3/54) had a residual effect on quality of life (OSA‐18 score > 60).

Conclusion

Adenotonsillectomy improves both objective and subjective outcomes. After surgery, quality of life significantly improved subjectively, despite an incomplete resolution of OSA objectively, leading to a better correlation between objective and subjective measures before as opposed to after surgery. Discrepancy between the 2 measures warrants an evaluation of a child both objectively and subjectively when treating OSA.
Long‐Term Outcomes in Sinus Surgery: A New Tool for Measuring Health‐Related Quality of Life
Authors: Remenschneider Aaron K. , D'Amico Laura , Litvack Jamie R. , Gray Stacey T. , Holbrook Eric H. , Gliklich Richard , Metson Ralph
Published: April 2014

Objective

The 6‐question EuroQol 5‐Dimension Health Assessment (EQ‐5D) is a widely used, simple instrument that monitors general health‐related quality of life (HRQoL) in chronic disease. It has not previously been applied to US patients undergoing endoscopic sinus surgery (ESS).

Study Design

Prospective cohort study.

Setting

Academic Medical Center.

Subjects and Methods

The study population consisted of 267 patients with chronic rhinosinusitis (CRS) who completed 2 disease‐specific instruments—the Chronic Sinusitis Survey (CSS) and the Sinonasal Outcomes Test‐22 (SNOT‐22)—and 1 general health‐related quality‐of‐life instrument—the EQ‐5D—before and after ESS for CRS. Baseline scores were compared to those collected 3 and 12 months after surgery and to the general US population.

Results

Surveys were completed at all time points by 186 patients, for a response rate of 69.7%. Patients with CRS, when compared to the US population, reported more problems in the domains of pain/discomfort (73.1% vs 40.8%, P <. 01), anxiety/depression (50.5% vs 26.4%, P <. 01), and usual activities (30.6% vs 15.0%, P <. 01). One year following ESS, there was a significant decrease in patients who reported problems with pain/discomfort (54.3%, P <. 001), anxiety/depression (30.6%, P <. 001), and usual activities (21.5%, P <. 01). After surgery, CRS anxiety/depression scores were no different from those of the US general population. Chronic Sinusitis Survey and SNOT‐22 scores demonstrated similar postoperative improvements.

Conclusion

The EQ‐5D assessment provides meaningful general health outcomes data with low patient burden. Application of this instrument demonstrated long‐term improvement in the quality of life of patients who undergo sinus surgery.
Balloon Dilation of the Cartilaginous Portion of the Eustachian Tube
Authors: Silvola Juha , Kivekäs Ilkka , Poe Dennis S.
Published: April 2014

Objective

Studies of balloon Eustachian tuboplasty (BET) have shown encouraging results in small series with short follow‐ups. Our pilot study suggested that patients with protracted otitis media with effusion (OME) or atelectasis of the tympanic membrane (TM) could benefit from BET.

Study Design

A prospective study where subjects act as their own controls. Patients from the pilot study and additional cases were enrolled in this cohort with long‐term follow‐up.

Setting

Regional Academic Center.

Subjects and Methods

Out of 80 patients who underwent BET, 41 consecutive Eustachian tube (ET) operations were included. Subjects’ inclusion criteria were OME and/or TM atelectasis, type B or C tympanograms, and inability to inflate their middle ears by Valsalva maneuver. All patients had longstanding ET dysfunction relieved only by repeated tympanostomies. Outcomes included ability to perform a Valsalva maneuver, audiometry, tympanometry, videoendoscopy of the ET with mucosal inflammation rating scores, and otomicroscopy.

Results

All cases were dilated successfully, without significant complications. Mean follow‐up was 2.5 years (range, 1.5‐4.2 years). Eighty percent (33/41) could do a Valsalva maneuver postoperatively; none of these ears required new tympanostomy tubes and subjective symptoms were relieved. Tympanometry results showed overall improvement. Nine patients had persistent perforations and 3 declined removal of the tube. Subjective symptoms were not relieved for 10% (4/41).

Conclusion

The results show that BET can effectively improve ET function in ears with OME or atelectasis. The procedure is well tolerated and without significant complications. The follow‐up continues and we are investigating possible reasons for failures.
Novel Peritonsillar Abscess Task Simulator
Authors: Taylor Steven R. , Chang C. W. David
Published: April 2014

The management of peritonsillar abscesses is a skill developed early in residency training. Although drainage is not technically complicated, the procedure is intimidating to the neophyte. Task simulators have become increasingly common to provide training opportunities in a controlled environment. The authors designed a peritonsillar abscess simulator using a latex moulage of the oral cavity and other common materials. Twelve medical professionals of various levels of experience were instructed to expose, anesthetize, aspirate, and drain the simulated abscess. After completion, a questionnaire was completed by each volunteer. Initial impressions were positive that the model adequately replicated the tasks requisite for abscess drainage and was suitable as an instructional device. The initial construct cost was approximately 10 dollars, with disposables costing roughly 25 cents. Further research is under way to formally assess the simulator for face, content, and construct validity.