bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of AMOR in Craniofacial Rabbit Bone Bioengineering
Authors: Freire Marcelo , Choi Jeong-Ho , Nguyen Anthony , Chee Young Deok , Kook Joong-Ki , You Hyung-Keun , Zadeh Homayoun H.
Published: January 2015

Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable ofin vivocapturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks,de novobone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significantin vivobone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models.
Rehabilitation of an Advanced Case of Adenoid Cystic Carcinoma
Authors: Volpato Luiz Evaristo Ricci , Caldas Lorena Frange , Castro Paulo Henrique de Souza , de Carvalhosa Artur Aburad , Volpato Maria Carmen Palma Faria , Bandéca Matheus Coelho , Borges Álvaro Henrique
Published: January 2015

Adenoid cystic carcinoma is a cancer of the salivary gland that primarily affects the parotid, submandibular, and accessory salivary glands. Its growth is slow and it has infiltrative nature. A 46-year-old female patient coming from the rural area presented a lesion on the palate and reported pain in the region for three years. After incisional biopsy, and histopathological diagnosis of adenoid cystic carcinoma of the cribriform type of minor salivary gland, superior hemimaxillectomy and adjuvant treatment with radiotherapy and maxillofacial prosthetic rehabilitation were performed.
Sativex in the Management of Multiple Sclerosis-Related Spasticity: Role of the Corticospinal Modulation
Authors: Russo Margherita , Calabrò Rocco Salvatore , Naro Antonino , Sessa Edoardo , Rifici Carmela , D’Aleo Giangaetano , Leo Antonino , De Luca Rosaria , Quartarone Angelo , Bramanti Placido
Published: January 2015

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, andHmax/Mmaxratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.
Submucosal Injection Solution for Endoscopic Resection in Gastrointestinal Tract: A Traditional and Network Meta-Analysis
Authors: Huai Zhang Yu , Feng Xian Wei , Chang Jiang Luo , Xi Chen Wang
Published: January 2015

Objective. To explore and define the current optimal submucosal injection solution used in ESD and EMR for gastrointestinal tract neoplasms in terms of clinical outcomes and other aspects.Methods. PubMed, Cochrane Library, Embase, and clinical trials register center were searched with terms of “endoscopic resection” and “submucosal injection solution” to identify relevant randomized controlled trials (RCTs). Both direct comparison using traditional meta-analysis method and indirect comparison using network meta-analysis method were performed.Results. A total of 11 RCTs with 1152 patients were included. Meta-analysis showed that, compared with normal saline, other submucosal injection solutions induced a significant increase in terms ofen blocresection rate(I2=0%, OR = 2.11, 95% CI (1.36, 3.26), andP= 0.008)and complete resection rate(I2=0%, OR = 2.14, 95% CI (1.41, 3.24), andP= 0.0003); and there was no significant difference in the incidence of total complications(I2=0%, OR = 0.87, 95% CI (0.59, 1.29), andP= 0.49).Conclusions. Other newly developed submucosal injection solutions significantly increaseden blocresection rate and complete resection rate and decreased bleeding rate and finical cost of endoscopic resection in gastrointestinal tract, while current evidence did not find the difference between them, which need to be explored by further studies.
The Importance of the Lifelike Esthetic Appearance of All-Ceramic Restorations on Anterior Teeth
Authors: dos Santos Daniela Micheline , Moreno Amália , Vechiato-Filho Aljomar José , Bonatto Liliane da Rocha , Pesqueira Aldiéris Alves , Laurindo Júnior Murilo César Bento , de Medeiros Rodrigo Antonio , Silva Emily Vivianne Freitas da , Goiato Marcelo Coelho
Published: January 2015

The success of rehabilitation will not depend on just clinical procedures. A proper dental technique (ceramist) is required as well as the respect for some biomimetic principles to obtain the desired final result. This study has the purpose of describing a prosthetic rehabilitation with laminate veneers and all-ceramic crowns of a patient unsatisfied with a previous esthetic treatment because of the negligence of some biomimetic principles. A 45-year-old female patient was admitted to the dental clinic complaining about the lifelike appearance of her all-ceramic restorations. Before the fabrication of new restorations, a mock-up was conducted to verify the patient’s satisfaction. A ceramist conducted all the fabrication process so that surface characterizations could be visually verified and the lifelike appearance of natural tooth could be reproduced. After the cementation procedure, the patient reported being satisfied with the lifelike appearance of the new restorations. Based on the clinical findings of the present case report, it can be concluded that the reproduction of the lifelike esthetic appearance of natural teeth and the visualization of the final results before definitive procedures are essential to obtain the clinical success.
Almost Periodic Time Scales and Almost Periodic Functions on Time Scales
Authors: Li Yongkun , Li Bing
Published: January 2015

We propose some new concepts of almost periodic time scales and almost periodic functions on time scales and give some basic properties of these new types of almost periodic time scales and almost periodic functions on time scales. We also give some comments on a recent paper by Wang and Agarwal (2014) concerning a new almost periodic time scale.
Diagnostic Accuracy of Mucosal Biopsy versus Endoscopic Mucosal Resection in Barrett’s Esophagus and Related Superficial Lesions
Authors: Elsadek Hany M. , Radwan Mamdouh M.
Published: January 2015

Background. Endoscopic surveillance for early detection of dysplastic or neoplastic changes in patients with Barrett's esophagus (BE) depends usually on biopsy. The diagnostic and therapeutic role of endoscopic mucosal resection (EMR) in BE is rapidly growing. Objective. The aim of this study was to check the accuracy of biopsy for precise histopathologic diagnosis of dysplasia and neoplasia, compared to EMR in patients having BE and related superficial esophageal lesions. Methods. A total of 48 patients with previously diagnosed BE (36 men, 12 women, mean age 49.75±13.3 years) underwent routine surveillance endoscopic examination. Biopsies were taken from superficial lesions, if present, and otherwise from BE segments. Then, EMR was performed within three weeks. Results. Biopsy based histopathologic diagnoses were nondysplastic BE (NDBE), 22 cases; low-grade dysplasia (LGD), 14 cases; high-grade dysplasia (HGD), 8 cases; intramucosal carcinoma (IMC), two cases; and invasive adenocarcinoma (IAC), two cases. EMR based diagnosis differed from biopsy based diagnosis (either upgrading or downgrading) in 20 cases (41.67%), (Kappa =0.43, 95% CI: 0.170–0.69). Conclusions. Biopsy is not a satisfactory method for accurate diagnosis of dysplastic or neoplastic changes in BE patients with or without suspicious superficial lesions. EMR should therefore be the preferred diagnostic method in such patients.
Pressure Flow Analysis in the Assessment of Preswallow Pharyngeal Bolus Presence in Dysphagia
Authors: Ferris Lara , Omari Taher , Selleslagh Margot , Dejaeger Eddy , Tack Jan , Vanbeckevoort Dirk , Rommel Nathalie
Published: January 2015

Objectives. Preswallow pharyngeal bolus presence is evident in patients with oropharyngeal dysphagia. Pressure flow analysis (PFA) using high resolution manometry with impedance (HRMI) with AIMplot software is a method for objective interpretation of pharyngeal and upper esophageal sphincter (UES) pressures and bolus flow patterns during swallowing. This study aimed to observe alterations in PFA metrics in the event of preswallow pharyngeal bolus presence as seen on videofluoroscopy (VFSS).Methods. Swallows from 40 broad dysphagia patients and 8 controls were recorded with a HRMI catheter during simultaneous VFSS. Evidence of bolus presence and level reached prior to pharyngeal swallow onset was recorded. AIMPlot software derived automated PFA functional metrics.Results. Patients with bolus movement to the pyriform sinuses had a higher SRI, indicating greater swallow dysfunction. Amongst individual metrics, TNadImp to PeakP was shorter and flow interval longer in patient groups compared to controls. A higher pharyngeal mean impedance and UES mean impedance differentiated the two patient groups.Conclusions. This pilot study identifies specific altered PFA metrics in patients demonstrating preswallow pharyngeal bolus presence to the pyriform sinuses. PFA metrics may be used to guide diagnosis and treatment of patients with oropharyngeal dysphagia and track changes in swallow function over time.
Organizing Pneumonia Associated with Pegylated Interferonαand Ribavirin Therapy
Authors: Chopra Amit , Marak Creticus , Alappan Narendrakumar , Shim Chang
Published: January 2015

Hepatitis C virus infection is the leading cause of chronic liver disease in the United States of America. Pegylated interferonαand ribavirin combination is the mainstay of treatment. Severe pulmonary toxicities are rarely reported. We report here a case of severe form of organizing pneumonia secondary to pegylated interferonαtherapy presenting as acute respiratory failure. Patient has near complete recovery with withdrawal of pegylated interferonαand steroid therapy. We report this case to raise the awareness of this rare but potentially life-threatening pulmonary complication of pegylated interferonαtherapy.
Ameloblastic Fibrodentinoma Presenting as a False Gingival Enlargement in the Maxillary Anterior Region
Authors: Joseph Shiny , Priya Lakshmi , Gopal Dinesh , Devachen Mary , Narayan Ajay , Afnan Muhammed
Published: January 2015

Ameloblastic fibrodentinoma is a rare benign mixed odontogenic neoplasm usually occurring in the first two decades of life. It is more common in males and the most common site of occurrence is in the mandibular premolar molar area. This report presents a case of ameloblastic fibrodentinoma in a 12-year-old boy in the maxillary anterior region, a less common site for the occurrence of ameloblastic fibrodentinoma. A 12-year-old boy presented with a midline diastema in 11 and 21 region and a swelling in the palatal aspect of 11 and 12. Intraoral periapical radiograph showed the presence of rarefaction of bone on the mesial aspect of the cervical and middle third of the root of 11. Excision biopsy was done. The specimen was processed and stained with hematoxylin and eosin. Microscopic examination showed islands, chords and strands of odontogenic epithelium in a primitive ectomesenchyme resembling dental papilla. The odontogenic epithelium exhibited peripheral ameloblast-like and central stellate reticulum-like cells. The presence of dentinoid material was seen adjacent to the odontogenic epithelium in some foci. The lesion was diagnosed as ameloblastic fibrodentinoma.
Australian Nurse Practitioner Practice: Value Adding through Clinical Reflexivity
Authors: Woods Michelle , Murfet Giuliana
Published: January 2015

The role of the Australian Nurse Practitioner (NP) is in its infancy and at a crossroads where extensive research demonstrates effective quality care and yet the role remains underrecognised and underutilised. The translation of practice into “value” is critical for the sustainability of NP roles and requires the practitioner to adopt a systematic method of inquiry. Kim’s (1999) “Critical Reflective Inquiry” (CRI) method was adapted by two Australian NPs who specialise in diabetes and chronic disease management. Kim highlights the intent of CRI as understanding the meaning of practice, delivering improvements to practice through self-reflection, and the critique of practice that can lead to practice changes and development of new models of care translated to “products” of value. Based on the thematically analysis of 3 years of CRI application, the authors formed 5 headings that represented the NP’s practice as Specialised Care Access, Complications and Diagnostics Interventions, Pharmaceutical Treatment, Vulnerable Populations, and Leadership. The utility of CRI demonstrates how NP practice is integral to a continuous cycle of addressing health care services gaps, and the conversion of “products” into “value” and positions the NP to assimilate the role of the practitioner-researcher.
Stability Criterion of Linear Stochastic Systems Subject to MixedH2/PassivityPerformance
Authors: Ku Cheung-Chieh , Lu Chih-Peng , Li Min-Ta
Published: January 2015

TheH2control scheme and passivity theory are applied to investigate the stability criterion of continuous-time linear stochastic system subject to mixed performance. Based on the stochastic differential equation, the stochastic behaviors can be described as multiplicative noise terms. For the considered system, theH2control scheme is applied to deal with the problem on minimizing output energy. And the asymptotical stability of the system can be guaranteed under desired initial conditions. Besides, the passivity theory is employed to constrain the effect of external disturbance on the system. Moreover, the Itô formula and Lyapunov function are used to derive the sufficient conditions which are converted into linear matrix inequality (LMI) form for applying convex optimization algorithm. Via solving the sufficient conditions, the state feedback controller can be established such that the asymptotical stability and mixed performance of the system are achieved in the mean square. Finally, the synchronous generator system is used to verify the effectiveness and applicability of the proposed design method.
The Risk Assessment of Sediment Heavy Metal Pollution in the East Dongting Lake Wetland
Authors: Hu Cong , Deng Zheng-miao , Xie Yong-hong , Chen Xin-sheng , Li Feng
Published: January 2015

Total concentrations of cadmium (Cd), lead (Pb), chrome (Cr), and nickel (Ni) in surface sediment (0–10 cm) from the East Dongting Lake wetlands were determined and the spatial distribution of heavy metals was mapped. The results showed that the single risk indices (Eri) of heavy metals were ranked in the order of Cd > Pb > Ni > Cr. The content of Cd and Pb was gradually reduced from the east (Xiangjiang River) to the west, while the Cr and Ni content had a patchy distribution pattern in the East Dongting Lake wetlands. Cd and Pb contents were correlated with soil pH significantly, while Cr and Ni contents were correlated with soil organic carbon (SOC) and total nitrogen (TN). The origination of heavy metal (Cd, Cr, Ni, and Pb) could be divided into two groups: Cd and Pb from anthropogenic source and Cr and Ni from parent material weathering. Our results indicated that Cd posed a high risk to local ecosystem. The relatively lower pH and higher soil organic carbon (SOC) and total nitrogen (TN) in sediment may inhibit the fixation of heavy metals, which in turn increased the concentration of heavy metal in sediment.
Dynamic Pricing for Airline Revenue Management under Passenger Mental Accounting
Authors: Hu Yusheng , Li Jinlin , Ran Lun
Published: January 2015

Mental accounting is a far-reaching concept, which is often used to explain various kinds of irrational behaviors in human decision making process. This paper investigates dynamic pricing problems for single-flight and multiple flights settings, respectively, where passengers may be affected by mental accounting. We analyze dynamic pricing problems by means of the dynamic programming method and obtain the optimal pricing strategies. Further, we analytically show that the passenger mental accounting depth has a positive effect on the flight’s expected revenue for the single flight and numerically illustrate that the passenger mental accounting depth has a positive effect on the optimal prices for the multiple flights.
Mining Association Rules in Dengue Gene Sequence with Latent Periodicity
Authors: Thangam Marimuthu , Vanniappan Balamurugan
Published: January 2015

The mining of periodic patterns in dengue database is an interesting research problem that can be used for predicting the future evolution of dengue viruses. In this paper, we propose an algorithm called Recurrence Finder (RECFIN) that uses the suffix tree for detecting the periodic patterns of dengue gene sequence. Also, the RECFIN finds the presence of palindrome which indicates the possibilities of formation of proteins. Further, this paper computes the periodicity of nucleic acid and amino acid sequences of any length. The periodicity based association rules are used to diagnose the type of dengue. The time complexity of the proposed algorithm is O(n2). We demonstrate the effectiveness of the proposed approach by comparing the experimental results performed on dengue virus serotypes dataset with NCBI-BLAST algorithm.
Semi-Iterative Method for Computing the Generalized InverseAT,S(2)
Authors: Liu Xiaoji , Jiang Caijing
Published: January 2015

The main aim of this paper is to compute the generalized inverseAT,S(2)over Banach spaces by using semi-iterative method and to present the error bounds of the semi-iterative method for approximatingAT,S(2).
A Fluorescence-Based Method for Rapid and Direct Determination of Polybrominated Diphenyl Ethers in Water
Authors: Shan Huimei , Liu Chongxuan , Wang Zheming , Ma Teng , Shang Jianying , Pan Duoqiang
Published: January 2015

A new method was developed for rapid and direct measurement of polybrominated diphenyl ethers (PBDEs) in aqueous samples using fluorescence spectroscopy. The fluorescence spectra of tri- to deca-BDE (BDE 28, 47, 99, 153, 190, and 209) commonly found in environment were measured at variable emission and excitation wavelengths. The results revealed that the PBDEs have distinct fluorescence spectral profiles and peak positions that can be exploited to identify these species and determine their concentrations in aqueous solutions. The detection limits as determined in deionized water spiked with PBDEs are 1.71–5.82 ng/L for BDE 28, BDE 47, BDE 190, and BDE 209 and 45.55–69.95 ng/L for BDE 99 and BDE 153. The effects of environmental variables including pH, humic substance, and groundwater chemical composition on PBDEs measurements were also investigated. These environmental variables affected fluorescence intensity, but their effect can be corrected through linear additivity and separation of spectral signal contribution. Compared with conventional GC-based analytical methods, the fluorescence spectroscopy method is more efficient as it only uses a small amount of samples (2–4 mL), avoids lengthy complicated concentration and extraction steps, and has a low detection limit of a few ng/L.
An Algorithm for Computing All Berge Equilibria
Authors: Corley H. W. , Kwain Phantipa
Published: January 2015

An algorithm is presented in this note for determining all Berge equilibria for an n-person game in normal form. This algorithm is based on the notion of disappointment, with the payoff matrix (PM) being transformed into a disappointment matrix (DM). The DM has the property that a pure strategy profile of the PM is a BE if and only if (0,…,0) is the corresponding entry of the DM. Furthermore, any (0,…,0) entry of the DM is also a more restrictive Berge-Vaisman equilibrium if and only if each player’s BE payoff is at least as large as the player’s maximin security level.
Deciphering Autoimmune Pancreatitis, a Great Mimicker: Case Report and Review of the Literature
Authors: Allaparthi Satya , Sageer Mohammed , Sterling Mark J.
Published: January 2015

Background. Autoimmune pancreatitis (AIP) is an atypical chronic inflammatory pancreatic disease that appears to involve autoimmune mechanisms. In recent years, AIP has presented as a new clinical entity with its protean pancreaticobiliary and systemic presentations. Its unique pathology and overlap of clinical and radiological features and absence of serological markers foster the disease’s unique position. We report a case of diffuse type 1 autoimmune pancreatitis with obstructive jaundice managed with biliary sphincterotomy, stent placement, and corticosteroids. A 50-year-old Caucasian woman presented to our hospital with epigastric pain, nausea, vomiting, and jaundice. Workup showed elevated liver function tests (LFT) suggestive of obstructive jaundice, MRCP done showed diffusely enlarged abnormal appearing pancreas with loss of normal lobulated contours, and IgG4 antibody level was 765 mg/dL. EUS revealed a diffusely hypoechoic and rounded pancreatic parenchyma with distal common bile duct (CBD) stricture and dilated proximal CBD and common hepatic duct (CHD). ERCP showed tight mid to distal CBD stricture that needed dilatation, sphincterotomy, and placement of stent that led to significant improvement in the symptoms and bilirubin level. Based on clinical, radiological, and immunological findings, a definitive diagnosis of AIP was made. Patient was started on prednisone 40 mg/day and she clinically responded in 4 weeks.
Contralateral Occlusion Increases the Risk of Neurological Complications Associated with Carotid Endarterectomy
Authors: Capoccia Laura , Sbarigia Enrico , Rizzo Anna Rita , Pranteda Chiara , Menna Danilo , Sirignano Pasqualino , Mansour Wassim , Esposito Andrea , Speziale Francesco
Published: January 2015

Objective. To report on the incidence and factors associated with the development of perioperative neurological complications following CEA in patients affected by carotid stenosis with contralateral occlusion (CO) and to compare results between those patients and the whole group of patients submitted to CEA at our vascular division from 1997 to 2012.Methods. Our nonrandomized prospective experience including 1639 patients consecutively submitted to CEA was retrospectively reviewed. 136 patients presented a CO contralateral to the treated carotid stenosis. Outcomes considered for analysis were perioperative neurological death rates, major and minor stroke rates, and a combined endpoint of all neurological complications.Results. CO patients more frequently were male, smokers, younger, and symptomatic (P< 0.001), presented with a preoperative brain infarct and associated peripheral arterial disease (P< 0.0001), and presented with higher perioperative major stroke rate than patients without CO (4.4% versus 1.2%, resp.,P= 0.009). Factors associated with the highest neurological risk in CO patients were age >74 years and preoperative brain infarct (P= 0.03). The combination of the abovementioned factors significantly increased complication rates in CO patients submitted to CEA.Conclusions. In our experience CO patients were at high risk for postoperative neurological complications particularly when presenting association of advanced age and preoperative brain infarction.
Primitive Neuroectodermal Tumor/Ewing Sarcoma Presenting with Pulmonary Nodular Lesions
Authors: Asker Selvi , Sayir Fuat , Bulut Gulay , Sunnetcioglu Aysel , Ekin Selami , Yavuz Alpaslan
Published: January 2015

Primitive neuroectodermal tumors (PNETs) and Ewing sarcoma (EWS) belong to the same family of malignant, small, round cell neoplasms of soft tissue or bone origin. EWS-PNETs that arise in the lung parenchyma involvement are extremely rare in adults. A case of a 32-year-old male presenting with chest pain and diffuse pulmonary nodules on chest X-ray and diagnosed with Ewing sarcoma-PNETs will be presented here.
Treatment and Outcomes of Urethral Recurrence of Urinary Bladder Cancer in Women after Radical Cystectomy and Orthotopic Neobladder: A Series of 12 Cases
Authors: Hrbáček Jan , Macek Petr , Ali-El-Dein Bedeir , Thalmann George N. , Stenzl Arnulf , Babjuk Marek , Shaaban Atallah A. , Gakis Georgios
Published: January 2015

Introduction: The incidence, treatment, and outcome of urethral recurrence (UR) after radical cystectomy (RC) for muscle-invasive bladder cancer with orthotopic neobladder in women have rarely been addressed in the literature. Patients and Methods: A total of 12 patients (median age at recurrence: 60 years) who experienced UR after RC with an orthotopic neobladder were selected for this study from a cohort of 456 women from participating institutions. The primary clinical and pathological characteristics at RC, including the manifestation of the UR and its treatment and outcome, were reviewed. Results: The primary bladder tumors in the 12 patients were urothelial carcinoma in 8 patients, squamous cell carcinoma and adenocarcinoma in 1 patient each, and mixed histology in 2 patients. Three patients (25%) had lymph node-positive disease at RC. The median time from RC to the detection of UR was 8 months (range 4-55). Eight recurrences manifested with clinical symptoms and 4 were detected during follow-up or during a diagnostic work-up for clinical symptoms caused by distant metastases. Treatment modalities were surgery, chemotherapy, radiotherapy, and bacillus Calmette-Guérin urethral instillations. Nine patients died of cancer. The median survival after the diagnosis of UR was 6 months. Conclusions: UR after RC with an orthotopic neobladder in females is rare. Solitary, noninvasive recurrences have a favorable prognosis when detected early. Invasive recurrences are often associated with local and distant metastases and have a poor prognosis.
Lipopolysaccharide-Induced Sickness Behavior in Lactating Rats Decreases Ultrasonic Vocalizations and Exacerbates Immune System Activity in Male Offspring
Authors: Nascimento Amanda F. , Alves Glaucie Jussilane , Massoco Cristina O. , Teodorov Elizabeth , Felicio Luciano F. , Bernardi Maria Martha
Published: January 2015

Objective: The present study analyzed the effects of lipopolysaccharide (LPS) on maternal behavior during lactation and possible correlations with changes in emotional and immune responses in offspring. Methods: Lactating rats received 100 μg/kg LPS, and the control group received saline solution on lactation day (LD) 3. Maternal general activity and maternal behavior were observed on LD5 (i.e. the day that the peak of fever occurred). In male pups, hematological parameters and ultrasonic vocalizations (USVs) were assessed on LD5. At weaning, an additional dose of LPS (50 µg/kg, i.p.) was administered in male pups, and open-field behavior, oxidative burst and phagocytosis were evaluated. Results: A reduction in the time in which dams retrieved the pups was observed, whereas no effects on maternal aggressive behavior were found. On LD5, a reduction of the frequency of USVs was observed in pups, but no signs of inflammation were found. At weaning, an increase in immune system activity was observed, but no differences in open-field behavior were found. Conclusion: These results indicate that inflammation in lactating mothers disrupted mother/pup interactions and may have produced short- and long-term effects on pup behavior as well as biological pathways that modulate inflammatory responses to bacterial endotoxin challenge in pups.
Lipopolysaccharide-Induced Maternal Inflammation Affects the Gonadotropin-Releasing Hormone Neuron Development in Fetal Mice
Authors: Sharova Victoria S. , Izvolskaia Marina S. , Zakharova Liudmila A.
Published: January 2015

Recent studies provide evidence that prenatal immunological stress may affect the programming of reproductive health and sexual behavior in adult animals. The aim of this study was to investigate the influence of maternal inflammation, induced by an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 45 µg/kg) on embryonic day 11.5 (E 11.5), on the development of the gonadotropin-releasing hormone (GnRH) system in mouse fetuses as well as on the proinflammatory cytokine level in pregnant mice and their fetuses. In the fetuses, the GnRH neuron migration from the olfactory pit to the forebrain was estimated on embryonic days 14.5 and 18.5. The levels of the proinflammatory cytokines interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α and leukemia inhibitory factor (LIF) were measured with the cytometric bead and ELISA array method in the maternal and fetal blood, amniotic fluid and fetal cerebrospinal fluid (CSF). According to our data, activation of the immune system by LPS treatment on embryonic day 11.5 leads to an increased quantity of neurons in the nasal and olfactory bulb areas and a decreased quantity in the forebrain area on embryonic day 14.5. There was a slight decrease in the total number of neurons in the forebrain area on embryonic day 18.5. The levels of proinflammatory cytokines were significantly increased within 3 h after LPS treatment in the maternal and fetal blood, amniotic fluid and fetal CSF. IL-6-receptor immunoreactivity was detected on olfactory/vomeronasal axons. Thus, prenatal immunological stress delays the GnRH neuron migration in the nasal compartment of mouse fetuses, which may be mediated by the regulation of IL-6, MCP-1 and LIF secretion in the maternal-fetal system.
Lipopolysaccharide-Stimulated Transglutaminase 2 Expression Enhances Endocytosis Activity in the Mouse Microglial Cell Line BV-2
Authors: Kawabe Kenji , Takano Katsura , Moriyama Mitsuaki , Nakamura Yoichi
Published: January 2015

Objectives: In peripheral macrophages, tissue-type transglutaminase (TG2) is reported to be involved in phagocytosis of apoptotic cells. However, the contribution of TG2 to microglial phagocytosis has not been investigated. In this study, using a microglial cell line, BV-2, we examined the changes in TG2 expression, phagocytosis and pinocytosis in cells stimulated by lipopolysaccharide (LPS). Methods: Cells of the mouse microglial cell line BV-2 were stimulated by LPS with or without cystamine, an inhibitor of TG enzyme activity, for 24 h. TG2 expression was measured by real-time RT-PCR and Western blotting. TG activity was evaluated using biotinylated pentylamine as a substrate. Pinocytosis was determined by uptake of 1-µm fluorescent microbeads. Phagocytosis was assessed by uptake of dead cells, human neuroblastoma SH-SY5Y cells, which were pretreated with H2O2 for 24 h. Results: Phagocytosis of dead cells and pinocytosis of fluorescent microbeads were up-regulated by LPS stimulation together with TG2 expression. Blockade of TG enzyme activity by cystamine suppressed TG2 expression, phagocytosis and pinocytosis. Conclusions: These results suggested that LPS-induced TG2 was involved in the mechanism of pinocytosis and phagocytosis in microglia.
Epithelial Ovarian Cancers and Endometriosis
Authors: Acién Pedro , Velasco Irene , Acién Maribel , Capello Cecilia , Vela Pilar
Published: January 2015

Aims: To determine the prevalence of endometriosis in epithelial ovarian cancers (EOC) and the association among their histological subtypes and with endometrial carcinoma. Methods: An observational cohort study performed in 192 patients operated on for EOC, 30 women with atypical endometriosis and 17 with p53 positive endometriosis. Data on associated endometriosis and endometrial carcinomas, histological subtypes, tumor stage, clinical and pathological characteristics and survival were analyzed. Results: Twenty cases of EOC (10.4%) had also endometriosis (12.7 in borderline and 9.3% in invasive cases), being a synchronous finding in most cases. Endometriosis associated with serous or mucinous EOC was observed in 2.2 and 2.7% of cases, respectively. However, this association was observed in 50 of endometrioid and 23% of clear cell EOC. Age, parity and tumor stage were lower in endometriosis-associated EOC patients; and all associated cases were type I (Kurman and Shih's classification) and showed better results in survival rate. Endometrial carcinoma was more frequently associated with endometrioid EOC (25%). Conclusions: There is a significant association between endometriosis, including atypical forms, and endometrioid and clear cell carcinomas, but not with other EOC histotypes. The presence of endometriosis in EOC suggests a better prognosis and an intermediate stage within the progression endometriosis-carcinoma.
Effects of Subcutaneous LPS Injection on Gestational Length and Intrauterine and Neonatal Mortality in Mice
Authors: Pujol Lopez Yara , Steinbusch Harry W.M. , Rutten Bart , Kenis Gunter , van den Hove Daniel L. , Myint Aye M.
Published: January 2015

Background: Infection during pregnancy can predispose offspring to develop various psychiatric disorders such as depression in later life. In order to investigate the potential mechanisms underlying these associations, animal models of maternal infection have been employed. As such, lipopolysaccharide (LPS) has been commonly used to mimic a bacterial infection in pregnant mice. Objective: The original aim of our study was to investigate the effects of different doses of subcutaneous LPS administration on affective behavior in adult mouse offspring. In the present paper, however, we report that subcutaneous LPS administration has a profound impact on gestational length, litter size, and perinatal mortality in the offspring, even at a relatively low dose. Methods: Pregnant mice were randomly divided into 3 groups, receiving either a high (2 mg/kg) or a low (0.5 mg/kg) dose of LPS or phosphate-buffered saline by means of subcutaneous injection. Subsequently, the effects on gestational length, litter size, and perinatal mortality in the offspring were assessed. Results: After subcutaneous injection with a high dose of LPS, we observed a significant decrease in gestational length and an increase in neonatal mortality. When the low dose was administered, a tendency towards a reduced litter size was observed, most likely reflecting increased intrauterine mortality in response to prenatal maternal LPS exposure. Conclusions: We showed that subcutaneous administration of 2 mg/kg LPS to pregnant mice in the last phase of gestation should be avoided because of high offspring mortality rates, whereas subcutaneous injection of 0.5 mg/kg LPS seems to result in reabsorption of the fetuses.
Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia
Authors: Bonestroo Hilde J.C. , Heijnen Cobi J. , Groenendaal Floris , van Bel Frank , Nijboer Cora H.
Published: January 2015

Antenatal inflammation is associated with increased severity of hypoxic-ischemic (HI) encephalopathy and adverse outcome in human neonates and experimental rodents. We investigated the effect of lipopolysaccharide (LPS) on the timing of HI-induced cerebral tissue loss and gray matter injury, white matter injury and integrity, and the cerebral inflammatory response. On postnatal day 9, mice underwent HI by unilateral carotid artery occlusion followed by systemic hypoxia which resulted in early neuronal damage (MAP2 loss) at 3 h that did not increase up to day 15. LPS injection 14 h before HI (LPS+HI) significantly and gradually aggravated MAP2 loss from 3 h up to day 15, resulting in an acellular cystic lesion. LPS+HI increased white matter damage, reduced myelination in the corpus callosum and increased white matter fiber coherency in the cingulum. The number of oligodendrocytes throughout the lineage (Olig2-positive) was increased whereas more mature myelinating (CNPase-positive) oligodendrocytes were strongly decreased after LPS+HI. LPS+HI induced an increased and prolonged expression of cerebral cytokines/chemokines compared to HI. Additionally, LPS+HI increased macrophage/microglia activation and influx of neutrophils in the brain compared to HI. This study demonstrates the sensitizing effect of LPS on neonatal HI brain injury for an extended time-frame up to 15 days postinsult. LPS before HI induced a gradual increase in gray and white matter deficits, including reduced numbers of more mature myelinating oligodendrocytes and a decrease in white matter integrity. Moreover, LPS+HI prolonged and intensified the cerebral inflammatory response, including cellular infiltration. In conclusion, as the timing of damage and/or involved pathways are changed when HI is preceded by inflammation, experimental therapies might require modifications in the time window, dosage or combinations of therapies for efficacious neuroprotection.
Safety and Efficacy of Sunitinib in Patients from Italy with Metastatic Renal Cell Carcinoma: Final Results from an Expanded-Access Trial
Authors: Sternberg Cora N. , Calabrò Fabio , Bracarda Sergio , Cartenì Giacomo , Lo Re Giovanni , Ruggeri Enzo M. , Basso Umberto , Gasparini Giampietro , Ciuffreda Libero , Ferrari Vittorio , Bonetti Andrea , Fea Elena , Gasparro Donatello , Tassinari Davide , Labianca Roberto , Masini Cristina , Fly Kolette , Zhang Ke , Hariharan Subramanian , Capaccetti Barbara , Porta Camillo
Published: January 2015

Objectives: Patients with metastatic renal cell carcinoma (mRCC) received sunitinib in a global expanded-access program (EAP). Here, we report the efficacy and safety results for the EAP subpopulation in Italy. Methods: Patients ≥18 years old with previously treated or treatment-naïve mRCC received oral sunitinib 50 mg/day on a 4-weeks-on/2-weeks-off schedule. Tumor measurements were scheduled per local practice (using Response Evaluation Criteria in Solid Tumors). Safety was regularly assessed. Results: A total of 521 patients participated, including 40% aged ≥65 years, 11% with an Eastern Cooperative Oncology Group performance status ≥2, 14% with non-clear cell RCC, and 11% with brain metastases. The median treatment duration and posttreatment follow-up were 7.4 and 12.3 months, respectively. The objective response rate was 12%, and the median progression-free and overall survival was 9.1 and 27.2 months, respectively. 514 patients (99%) discontinued treatment; reasons included death (17%), nonresponse (46%), or adverse events (AEs; 13%). The most common any-grade treatment-related AEs were asthenia (44%, plus 15% reporting fatigue), thrombocytopenia and stomatitis (both 37%), diarrhea (36%), mucosal inflammation (29%), hypertension (26%), and dysgeusia (25%). The most common grade 3/4 treatment-related AEs were thrombocytopenia (10%), asthenia (9%, plus 3% reporting fatigue), neutropenia, stomatitis (both 6%), and hypertension (5%). Conclusion: In a large population of Italian mRCC patients, sunitinib had a manageable safety profile and encouraging efficacy.
Molecular Markers for Bladder Cancer Screening, Early Diagnosis, and Surveillance: The WHO/ICUD Consensus
Authors: Schmitz-Dräger Bernd J. , Droller Michael , Lokeshwar Vinata B. , Lotan Yair , Hudson M''Liss A. , van Rhijn Bas W. , Marberger Michael J. , Fradet Yves , Hemstreet George P. , Malmstrom Per-Uno , Ogawa Osamu , Karakiewicz Pierre I. , Shariat Shahrokh F.
Published: January 2015

Due to the lack of disease-specific symptoms, diagnosis and follow-up of bladder cancer has remained a challenge to the urologic community. Cystoscopy, commonly accepted as a gold standard for the detection of bladder cancer, is invasive and relatively expensive, while urine cytology is of limited value specifically in low-grade disease. Over the last decades, numerous molecular assays for the diagnosis of urothelial cancer have been developed and investigated with regard to their clinical use. However, although all of these assays have been shown to have superior sensitivity as compared to urine cytology, none of them has been included in clinical guidelines. The key reason for this situation is that none of the assays has been included into clinical decision-making so far. We reviewed the current status and performance of modern molecular urine tests following systematic analysis of the value and limitations of commercially available assays. Despite considerable advances in recent years, the authors feel that at this stage the added value of molecular markers for the diagnosis of urothelial tumors has not yet been identified. Current data suggest that some of these markers may have the potential to play a role in screening and surveillance of bladder cancer. Well-designed protocols and prospective, controlled trials will be needed to provide the basis to determine whether integration of molecular markers into clinical decision-making will be of value in the future.
Gastroesophageal Reflux Disease Is a Risk Factor for Severity of Organizing Pneumonia
Authors: Gaillet Geoffrey , Favelle Olivier , Guilleminault Laurent , de Muret Anne , Lemarie Etienne , Lecomte Thierry , Marchand-Adam Sylvain , Diot Patrice
Published: January 2015

Background: The link between organizing pneumonia (OP) and gastroesophageal reflux disease (GERD) is not well known. There is little evidence in the literature to establish a causal link between GERD and OP. Objectives: The aim of the study was to assess the hypothesis that OP is more severe when it is associated with GERD and that it leads to more frequent relapses. Methods: In a retrospective study on 44 patients suffering from OP, we compared the clinical, radiological and histological characteristics of 2 groups, 1 composed of patients with GERD (n = 20) and the other of patients without GERD (n = 24). Results: The GERD group was distinguished by a higher number of patients with migratory alveolar opacities on chest radiography and thoracic computerized tomography (14/20 vs. 9/24; p = 0.03 and 18/20 vs. 13/24; p = 0.01), greater hypoxemia [60 (42-80) vs. 70 (51-112) mm Hg; p = 0.03], greater bronchoalveolar lavage cellularity [0.255 (0.1-1.8) vs. 0.150 (0.05-0.4) g/l; p = 0.035] and more frequent relapses (14/20 vs. 9/24; p = 0.03). Conclusions: OP associated with GERD is more severe and results in more frequent relapses. Microinhalation of gastric secretions might induce lung inflammation leading to OP and relapse. We suggest that typical symptoms of GERD such as pyrosis should be investigated in OP.
Tumor Bed Boost Integration during Whole Breast Radiotherapy: A Review of the Current Evidence
Authors: Franco Pierfrancesco , Cante Domenico , Sciacero Piera , Girelli Giuseppe , La Porta Maria Rosa , Ricardi Umberto
Published: January 2015

Radiation therapy delivered with hypofractionation, which involves the delivery of a higher dose per fraction in fewer fractions (generally with a lower total nominal dose) over a shorter overall treatment time, is an established therapeutic option at least for a selected group of early breast cancer patients after breast-conserving surgery. Optimal delivery of the tumor bed boost dose in terms of timing, fractionation, and total dose whenever a hypofractionated schedule is employed has yet to be established. We herein present a review of the current evidence on the role of boost integration in whole breast radiotherapy.
Clinical Management of Pregnancy in Women with Goodpasture Syndrome
Authors: Huser Martin , Wagnerova Kristyna , Janku Petr , Malaskova Lenka , Stourac Petr
Published: January 2015

Background/Aims: Goodpasture syndrome (GS) is an autoimmune disease affecting mainly the kidneys and lungs. This review article focuses on GS occurring during pregnancy, which can seriously threaten the lives of both mother and fetus. We summarize the current clinical diagnosis and management of GS in pregnancy. Methods: A profound literature search was carried out to review all published articles or case studies reporting on GS in pregnancy. We extracted the following data from each case: patient age, parity, gestational age, therapy of GS during pregnancy, pregnancy outcome, neonatal outcome, mode of delivery, and the patient's kidney status. We describe in detail how a recent case of GS diagnosed in pregnancy was successfully treated. Results: A review of the available literature revealed 4 cases of GS in pregnancy. The average patient age was 29.3 ± 2.5 years, and most were primiparous, with an average parity of 1.3 ± 1.5. The average gestational age at the time of diagnosis was 12.5 ± 5.9 weeks. The therapies of GS during pregnancy were remarkably varied. Furthermore, the neonatal outcomes were also quite individual among the observed cases. Conclusion: The occurrence of GS during pregnancy is very rare. This unusual pregnancy complication is associated with significant maternal and fetal morbidity. The management of GS during pregnancy requires intensive care and multidisciplinary cooperation.
Eosinophilic Otitis Media Is Associated with Asthma Severity and Smoking History
Authors: Seo Yukako , Nonaka Manabu , Tagaya Etsuko , Tamaoki Jun , Yoshihara Toshio
Published: January 2015

Purpose: Eosinophilic otitis media (EOM) is an intractable otitis media characterized by an accumulation of eosinophils in the middle ear and a strong association with asthma. We investigated the relationship between EOM and asthma severity, asthma risk factors, lung function, and airway structural changes assessed by high-resolution computed tomographic (HRCT) scanning. Materials and Methods: Forty-one asthma patients with chronic rhinosinusitis (18 men and 23 women; mean age 56 years; age range 25-82 years) were included in this study. EOM was diagnosed according to the published diagnostic criteria. Asthma severity and risk factors for asthma, such as smoking history (Brinkman index, BI), were examined. Airway wall thickness and emphysema were assessed with HRCT scanning by a blinded respiratory specialist using a validated method. Lung function was measured using standard procedures. Results: EOM was diagnosed in 34% of the patients. Asthma severity, BI and airway wall thickness were each statistically greater in patients with EOM than in patients without EOM. Conclusion: There was a close relationship between EOM and asthma severity in asthma patients with chronic rhinosinusitis. Cessation of smoking might help prevent EOM by reducing airway wall thickness.