bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Androgen Blockade on HER‐2 and Matrix Metalloproteinase‐2 Expression on Bone Marrow Micrometastasis and Stromal Cells in Men with Prostate Cancer
Authors: Murray N. P. , Reyes E. , Badinez L. , Orellana N. , Fuentealba C. , Olivares R. , Porcell J. , Dueñas R.
Published: May 2013

Introduction. HER‐2 has been associated with castrate resistant prostate cancer and matrix metalloproteinase‐2 (MMP‐2) in the dissemination and invasion of tumor cells as well as activating angiogenesis. We present an immunocytochemical study of the effect of androgen blockade on the expression of HER‐2 and MMP‐2 in bone marrow micrometastasis and the surrounding stromal cells in men with prostate cancer. Methods and Patients. A cross‐sectional study of men with prostate cancer. Touch preps were obtained from bone marrow biopsies of men with prostate cancer, before and after radical prostatectomy and during androgen blockade. Micrometastasis detected with anti‐PSA immunocytochemistry underwent processing with anti‐HER‐2 and anti‐MMP‐2 immunocytochemistry. Patients were defined as HER‐2 positive or negative, MMP‐2 negative or an MMP‐2 pattern described as border or central and stromal MMP‐2 defined as positive or negative. The expression of the biomarkers was compared before and after primary treatment and during androgen blockade in relation to the serum PSA at the time of sampling and duration of androgen blockade. Results. 191 men participated, 35 men before surgery and 43 after surgery; there were no significant differences in HER‐2 expression between groups, there was no MMP‐2 expression centrally or stromal expression of MMP‐2. In men with androgen blockade, HER‐2 expression was significantly higher; there was a trend for increasing HER‐2 expression up to 5 years; central MMP‐2 expression significantly increased after 3 years, while stromal MMP‐2 significantly increased after 6 years. MMP‐2 expression both in micrometastasis and stroma was significantly associated with HER‐2 expression. Expression of MMP‐2 at the border of the micrometastasis was not associated with HER‐2 expression and occurred in the absence of androgen blockade.
Conclusions. Androgen blockade decreases serum PSA by eliminating HER‐2 negative prostate cancer cells. However, there is early selection of HER‐2 positive cancer cells which leads to androgen independence and to increased expression of MMP‐2 activity in the micrometastasis. The increased MMP‐2 activity in the micrometastasis increases the expression of MMP‐2 in the surrounding stromal cells and thus could promote angiogenesis and tumor growth resulting in macrometastatic androgen independent disease.
A Mathematical Programming Model for Cell Formation Problem with Machine Replication
Authors: Raminfar Reza , Zulkifli Norzima , Vasili Mohammadreza
Published: May 2013

Cell formation (CF) is a crucial aspect in the design of cellular manufacturing (CM) systems. This paper develops a comprehensive mathematical programming model for the cell formation problem, where product demands, cell size limits, sequence of operations, multiple units of identical machines, machine capacity, or machine cost are all considered. In this model, the intercell moves are restricted to be unidirectional from one cell to the downstream cells, without backtracking. The proposed model is investigated through several numerical examples. To evaluate the solution quality of the proposed model, it is compared with some well-known cell formation methods from the literature, by using group capability index (GCI) as a performance measure. The results and comparisons indicate that the proposed model produces solution with a higher performance.
Rapid Identification of the Multiple Absorbed Bioactive Components and Metabolites in Rat Serum after Oral Administration of Wu-Jia Sheng-Hua Capsule by UPLC-ESI-MS
Authors: Geng Fang , Wang Fashan , Zou Taobo , Zhu Kuiyuan , Ma Wei , Tan Guanghui , Zhang Ning
Published: May 2013

To identify the compounds absorbed in rat serum after the oral administration of Wu-Jia Sheng-Hua (WJSH) capsule, a traditional Chinese medicine (TCM) compound prescription, an ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC/ESI-MS) method, was established. The chromatographic separation of the absorbed compounds and metabolites was achieved with an ACQUITY UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm) under a gradient elution. The mobile phase was composed of acetonitrile and water buffered with ammonium acetate (10 mM) and formic acid (0.1%, V/V). Twelve absorbed compounds and four metabolites were found. Seven of the absorbed compounds were identified by ESI-MS. The identification of absorbed compounds might be helpful for the better understanding of the mechanisms underlying the pharmacological effects of WJSH capsule.
Aggressive Waves in the Lemon-Clawed Fiddler Crab (Uca perplexa): A Regional “Dialect” in Fiji
Authors: Weis Judith S. , Weis Peddrick
Published: May 2013

A population of the lemon-clawed fiddler crab (U. perplexa) in Fiji (island of Vanua Levu) was studied for types of communication (i.e., signaling via waving the male’s larger claw). Two types of signals were observed. In addition to the expected territorial display of a large and complex vertical wave that conveys its message over a typical distance of 10–40 cm (with large males signaling to other large males over the greatest distance), a short, rapid, and horizontal wave was typically directed over a much shorter distance, rarely exceeding 10 cm. This latter wave type, seemingly of an aggressive nature, differs from the vertically directed aggressive signal observed in an Australian population of this species and thus appears to be a regional “dialect” for this mode of communication.
Extracting Physicochemical Features to Predict Protein Secondary Structure
Authors: Huang Yin-Fu , Chen Shu-Ying
Published: May 2013

We propose a protein secondary structure prediction method based on position‐specific scoring matrix (PSSM) profiles and four physicochemical features including conformation parameters, net charges, hydrophobic, and side chain mass. First, the SVM with the optimal window size and the optimal parameters of the kernel function is found. Then, we train the SVM using the PSSM profiles generated from PSI‐BLAST and the physicochemical features extracted from the CB513 data set. Finally, we use the filter to refine the predicted results from the trained SVM. For all the performance measures of our method, Q3 reaches 79.52, SOV94 reaches 86.10, and SOV99 reaches 74.60; all the measures are higher than those of the SVMpsi method and the SVMfreq method. This validates that considering these physicochemical features in predicting protein secondary structure would exhibit better performances.
Drug-Induced Liver Injury Caused by Adalimumab: A Case Report and Review of the Bibliography
Authors: Frider Bernardo , Bruno Andres , Ponte Marcelo , Amante Marcelo
Published: May 2013

The most serious adverse drug reaction of adalimumab (ADR) is tuberculosis reactivation. We describe a case of a 35-year-old man, with rheumatoid arthritis (RA) and hepatitis C virus genotype 1a with a liver biopsy in 2001 with a METAVIR score pattern A1 F0; he received interferon alpha 2b for six months, but treatment was suspended because of reactivation of RA. Liver function tests after treatment were similar to previous ones showing a minimal cholestatic pattern. In 2008, methotrexate was prescribed, but the drug was withdrawn at the third month because of the appearance of pruritus and Ggt rise. Viral load at that moment was 9300000 UI/mL, log 6,9. The liver biopsy showed a Metavir Score A2 F1. Adalimumab was started in 2010, and at the third month of treatment, Ggt showed a rise of 23 times normal value (NV), alkaline phosphatase 2,5 times NV with AST and ALT with no change. A new liver biopsy showed portal inflammation with eosinophils and a METAVIR A1 F2. We think that adalimumab appears to be responsible for the liver injury, because of temporal relationship, liver biopsy findings, other clinical conditions being discarded, and the improvement of clinical symptoms and biochemical abnormalities when adalimumab was suspended.
Precise and Accurate Job Cycle Time Forecasting in a Wafer Fabrication Factory with a Fuzzy Data Mining Approach
Authors: Chen Toly , Romanowski Richard
Published: May 2013

Many data mining methods have been proposed to improve the precision and accuracy of job cycle time forecasts for wafer fabrication factories. This study presents a fuzzy data mining approach based on an innovative fuzzy backpropagation network (FBPN) that determines the lower and upper bounds of the job cycle time. Forecasting accuracy is also significantly improved by a combination of principal component analysis (PCA), fuzzy c-means (FCM), and FBPN. An applied case that uses data collected from a wafer fabrication factory illustrates this fuzzy data mining approach. For this applied case, the proposed methodology performs better than six existing data mining approaches.
A New Distance Measure and Ranking Method for Generalized Trapezoidal Fuzzy Numbers
Authors: Allahviranloo T. , Jahantigh M. A. , Hajighasemi S.
Published: May 2013

This study presents an approximate approach for ranking fuzzy numbers based on the centroid point of a fuzzy number and its area. The total approximate is determined by convex combining of fuzzy number’s relative and its area that is based on decision maker’s optimistic perspectives. The proposed approach is simple in terms of computational efforts and is efficient in ranking a large quantity of fuzzy numbers. A group of examples by Bortolan and Degani (1985) demonstrate the accuracy and applicability of the proposed approach. Finally by this approach, a new measure is introduced between two fuzzy numbers.
Dentinal Dysplasia Type I: A Case Report with a 6-Year Followup
Authors: Ozer Sezin , Ozden Bora , Otan Ozden Feyza , Gunduz Kaan
Published: May 2013

Introduction. Dentin dysplasia is a rare disturbance of dentin formation characterized by normal enamel but atypical dentin formation with abnormal pulpal morphology that is inherited as an autosomal pulpal morphology.Case Presentation. A 7-year-old female who had problems in chewing function was referred to Oral and Maxillofacial Surgery Department at the Faculty of Dentistry in Ondokuz Mayıs University. In the radiographic examination, it was determined that some of the unerupted permanent teeth of the patient had short, blunted, and malformed roots with obliterated pulp chambers, although the bone below the teeth showed well-defined margins. This unusual case of generalized short roots presents a case demonstrating both classic and atypical features of dentinal dysplasia type I (DDI) in the mixed and permanent dentitions.Conclusion. There are still many issues in the diagnosis and management of patients with dentin dysplasia. Early diagnosis, clinical and radiographic findings, as well as treatment of this condition and the initiation of effective preventive strategies may help prevent or delay loss of dentition.
Oxidative Stress in the Pathogenesis of Colorectal Cancer: Cause or Consequence?
Authors: Perše Martina
Published: May 2013

There is a growing support for the concept that reactive oxygen species, which are known to be implicated in a range of diseases, may be important progenitors in carcinogenesis, including colorectal cancer (CRC). CRC is one of the most common cancers worldwide, with the highest incidence rates in western countries. Sporadic human CRC may be attributable to various environmental and lifestyle factors, such as dietary habits, obesity, and physical inactivity. In the last decades, association between oxidative stress and CRC has been intensively studied. Recently, numerous genetic and lifestyle factors that can affect an individual's ability to respond to oxidative stress have been identified. The aim of this paper is to review evidence linking oxidative stress to CRC and to provide essential background information for accurate interpretation of future research on oxidative stress and CRC risk. Brief introduction of different endogenous and exogenous factors that may influence oxidative status and modulate the ability of gut epithelial cells to cope with damaging metabolic challenges is also provided.
Computational Study of Estrogen Receptor-Alpha Antagonist with Three-Dimensional Quantitative Structure-Activity Relationship, Support Vector Regression, and Linear Regression Methods
Authors: Chang Ying-Hsin , Chen Jun-Yan , Hor Chiou-Yi , Chuang Yu-Chung , Yang Chang-Biau , Yang Chia-Ning
Published: May 2013

Human estrogen receptor (ER) isoforms, ERαand ERβ, have long been an important focus in the field of biology. To better understand the structural features associated with the binding of ERαligands to ERαand modulate their function, several QSAR models, including CoMFA, CoMSIA, SVR, and LR methods, have been employed to predict the inhibitory activity of 68 raloxifene derivatives. In the SVR and LR modeling, 11 descriptors were selected through feature ranking and sequential feature addition/deletion to generate equations to predict the inhibitory activity toward ERα. Among four descriptors that constantly appear in various generated equations, two agree with CoMFA and CoMSIA steric fields and another two can be correlated to a calculated electrostatic potential of ERα.
Low-Grade Central Osteosarcoma of the Rib: A Case Report and Brief Review of the Literature
Authors: Moghadamfalahi Mana , Alatassi Houda
Published: May 2013

Low-grade central osteosarcoma is a rare variant of osteosarcoma which comprises less than 1-2% of all osteosarcomas. Most low-grade osteosarcomas involve long bones, most commonly distal femur, and proximal tibia. Histologically this tumor is difficult to diagnose, and an unusual location makes this diagnosis even more challenging. Here we report a case of low-grade osteosarcoma presenting as a chest wall mass involving the left 6th–8th ribs. This unusual site of presentation significantly added to the diagnostic difficulties of this rare tumor with challenging histologic features. To the best of our knowledge, only six cases of low-grade central osteosarcoma of the ribs have been reported in the English literature.
The Cardioprotective Effects of Citric Acid and L-Malic Acid on Myocardial Ischemia/Reperfusion Injury
Authors: Tang Xilan , Liu Jianxun , Dong Wei , Li Peng , Li Lei , Lin Chengren , Zheng Yongqiu , Hou Jincai , Li Dan
Published: May 2013

Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components ofFructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. Inin vivorat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation.In vitroexperiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient ofFructus Choerospondiatisresponsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease.
Remote Teleoperated and Autonomous Mobile Security Robot Development in Ship Environment
Authors: Chung Long-Yeu
Published: May 2013

We propose a wireless remote teleoperated and autonomous mobile security robot based on a multisensor system to monitor the ship/cabin environment. By doing this, pilots in charge of monitoring can be away from the scene and feel like being at the site monitoring and responding to any potential safety problems. Also, this robot can be a supplementary device for safety cabin crew members who are very busy and/or very tired of properly responding to crises. This can make one crew member on duty at the cabin a possible option. In fact, when the robot detects something unusual in the cabin, it can also notify the pilot so that the pilot can teleoperate the robot to response to whatever is needed. As a result, a cabin without any crew members on duty can be achieved through this type of robot/system.
Hypoglycemic and Hypolipidemic Potential of a High Fiber Diet in Healthy versus Diabetic Rabbits
Authors: Díez Raquel , García Juan J. , Diez M. José , Sierra Matilde , Sahagún Ana M. , Calle Ángela P. , Fernández Nélida
Published: May 2013

The aim of this study was to investigate potential hypoglycaemic and hypolipidemic effects of Plantago ovata husk included in the diet, in healthy and diabetic rabbits. We also examined the effects of this fiber in other biochemical parameters. Two groups of 18 rabbits were used. The first group was fed with standard chow and the second with chow supplemented with Plantago ovata husk (3.5 mg/kg/day). On day 14 diabetes mellitus was induced by the intravenous administration of alloxan (80 mg/kg). After an oral glucose load (3 g), glucose, insulin, and other biochemical parameters were determined on day 14 (healthy rabbits) and on day 28 (diabetic rabbits). In healthy rabbits, fiber did not modify glucose or insulin levels but decreased significantly total cholesterol, LDL-cholesterol, atherogenic index, and glycosylated hemoglobin. In diabetic rabbits, fiber was more beneficial in mild diabetics than in severe diabetics with significant decreases in glucose levels and increases in insulin concentrations. In these animals fiber caused an important reduction in cholesterol, indicating a beneficial effect of Plantago ovata husk in diabetic rabbits. Although further studies in patients are necessary, we think that Plantago ovata husk offers interesting perspectives to be administered to patients with diabetes mellitus.
Application of Homotopy Perturbation Method with an Auxiliary Term for Nonlinear Dropping Equations Arisen in Polymer Packaging System
Authors: Hong Xiang , Wang Jun , Lu Li-xin
Published: May 2013

The homotopy perturbation method (HPM) with an auxiliary term was applied to obtain approximate analytical solutions of polymer cushioning packaging system. The second-order solution of the equation of motion was obtained and compared with the numerical simulation solution solved by the Runge-Kutta algorithm. The results showed the high accuracy of this modified HPM with convenient calculation.
Adult Serum Cytokine Concentrations and the Persistence of Asthma
Authors: Kandane-Rathnayake R.K. , Tang M.L.K. , Simpson J.A. , Burgess J.A. , Mészáros D. , Feather I. , Southey M.C. , Schroen C.J. , Hopper J. , Morrison S.C. , Giles G.G. , Walters E.H. , Dharmage S.C. , Matheson M.C.
Published: May 2013

Background: Cytokines play a pivotal role in regulating the development and persistence of the inflammatory process in asthma. Our aim was to investigate whether asthma persistence or remission is associated with a specific cytokine profile. Methods: The Tasmanian Longitudinal Health Study followed participants from 7 to 44 years of age. Serum concentrations of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha (TNF-α) were measured at age 44 years. Participants were categorized into five phenotypes (early-onset noncurrent asthma, early-onset current asthma, late-onset noncurrent asthma and late-onset current asthma). Those who had never had asthma formed the reference group. Multivariable linear regression was used to compare serum cytokine concentrations between each phenotype and the reference group. Results: IL-10 concentrations were significantly lower in serum from the early-onset current asthma group than in the reference group (ratio of geometric means 0.58; 95% confidence interval 0.33-0.99; p = 0.048). IL-6 concentrations for the late-onset remitted group were also significantly lower than in the reference group (p = 0.009). The TNF-α concentrations were significantly lower for both early-and late-onset remitted asthma phenotypes when compared with the reference group. No associations were detected between serum concentrations of IL-4, IL-5 or IL-8 and these specific longitudinal asthma phenotypes. Conclusion: Our findings suggest a possible role for deficient IL-10 responses in the persistence of early-onset asthma. Lower IL-6 and TNF-α concentrations in serum from those with remitted asthma suggest that these proinflammatory cytokines may be actively suppressed during asthma remission.
Identification of Novel Allergenic Components from German Cockroach Fecal Extract by a Proteomic Approach
Authors: Jeong Kyoung Yong , Kim Chung-ryul , Park Jina , Han In-Soo , Park Jung-Won , Yong Tai-Soon
Published: May 2013

Background: Cockroaches produce potent allergens, and cockroach feces are known to be especially rich in allergens. In this study, we analyze the allergenic components from cockroach feces and evaluate allergenicity of recombinant α-amylase identified from fecal extract. Methods: IgE-reactive proteins from German cockroach fecal extract were analyzed by proteomic analysis and immunoblotting. Recombinant α-amylase was produced and its allergenicity was evaluated by ELISA. Results: Analysis of German cockroach fecal extracts identified 12 IgE-reactive components. Most of these allergens were found to be digestive enzymes such as α-amylase, trypsin, chymotrypsin, metalloprotease, and midgut carboxypeptidase A, but the identity of 3 IgE-reactive proteins is still unknown. Glycinin-like proteins, which were likely derived from the cockroach diet, were also identified. German cockroach α-amylase shares the highest identity with pig α-amylase (55.8%), followed by mite group 4 allergens (Blo t 4, 50.4%; Der p 4, 49.8%; Eur m 4, 47.4%). In this study, recombinant α-amylase from German cockroach was expressed, and its allergenicity was examined by ELISA. Specific IgE against recombinant amylase was detected in 41.4% (12/29) of serum samples from German cockroach-sensitized subjects. Recombinant α-amylase was able to inhibit 55% of specific IgE to German cockroach whole-body extract. Conclusions: Amylase was found to be an important novel allergen in cockroach feces. It is hoped that recombinant α-amylase will be useful for further studies and clinical applications.
Immunotherapy with a Recombinant Hybrid Molecule Alleviates Allergic Responses More Efficiently than an Allergenic Cocktail or Pollen Extract in a Model of Chenopodium album Allergy
Authors: Nouri Hamid Reza , Sankian Mojtaba , Afsharzadeh Danial , Varasteh Abdolreza
Published: May 2013

Background: The aim of this study is to assess the therapeutic potential of a recombinant hybrid molecule (rHM) alongside an allergenic cocktail from recombinant wild-type allergens as well as pollen extract on Chenopodium album allergy, using a BALB/c mouse model. Methods: The BALB/c mice had already been sensitized to C. album via intraperitoneal injections of alum-adsorbed allergenic cocktail and immunotherapy procedure was followed by subcutaneous injections of the rHM, allergenic cocktail and pollen extract at weekly intervals. Humoral immune responses were determined via measurement of specific antibodies in serum. Splenocytes of immunized mice were stimulated in vitro and then proliferation responses, cytokine secretion and mRNA expression of genes involved in immunotherapy were examined by ELISA and real-time PCR. Results: Sensitized mice were identified with high specific IgE against allergenic cocktail when compared with healthy mice. Immunotherapy with the rHM induced the highest ratio of the IgG2a/IgG1 levels compared to allergenic cocktail or C. album pollen extract. The rHM was able to induce proliferative responses as well as the allergenic cocktail in cultured splenocytes. Immunotherapy with the rHM significantly improved secretion of IFN-γ and IL-10, while secretion of IL-13 rapidly diminished. Interestingly, mRNA expression of GATA3 was strongly decreased in rHM-treated mice whereas mRNA expression of T-bet and Foxp3 was significantly increased. Conclusion: Our results prove that immunotherapy with the rHM effectively controlled allergic responses by shifting from a Th2-like immune response to a Th1-dominated immune response.
Intranasal, Liposome-Adjuvanted Cockroach Allergy Vaccines Made of Refined Major Allergen and Whole-Body Extract of Periplaneta americana
Authors: Meechan Panissara , Tungtrongchitr Anchalee , Chaisri Urai , Maklon Khuanwalai , Indrawattana Nitaya , Chaicumpa Wanpen , Sookrung Nitat
Published: May 2013

Background: Cockroach (CR) allergens frequently cause severe asthma in CR-sensitized subjects. Allergen-specific immunotherapy causes a shift of allergic Th2 responses towards Th1 and/or regulatory T cell (Treg) responses which reduce airway inflammation and prevent disease progression. Data are relatively limited on immunotherapy via CR allergy vaccine. Methods: The therapeutic efficacy of an intranasal liposome-adjuvant vaccine made of a refined Periplaneta americana arginine kinase (AK) was compared to the liposome-entrapped P. americana crude extract (CRE) vaccine. Adult BALB/c mice were rendered allergic to CRE. Three allergic mouse groups were immunized intranasally on alternate days with 8 doses of liposome-entrapped CRE (L-CRE), liposome-entrapped AK and placebo, respectively. One week later, all mice received a nebulized CRE provocation. Evaluation of vaccine efficacy was performed 1 day after provocation. Results: Liposome-entrapped native AK attenuated airway inflammation after the CRE provocation and caused a shift of allergic Th2 to Th1 and Treg responses. The L-CRE also induced a shift from the Th2 to the Th1 response but did not induce a Treg response and could not attenuate the airway inflammation upon allergen reexposure. Conclusions: Intranasal liposome-adjuvant CR allergy vaccine containing native AK (Per a 9) is better than L-CRE in attenuating allergic airway inflammation. The findings of this study not only document a more comprehensive and beneficial immune response induced by the refined allergen vaccine but also raise the point that the shift from the Th2 to the Th1 response alone might not correlate with improved airway histopathology, clinical outcome and quality of life.
Structural and Functional Assessment of Macula in Patients with High-Risk Proliferative Diabetic Retinopathy Submitted to Panretinal Photocoagulation and Associated Intravitreal Bevacizumab Injections: A Comparative, Randomised, Controlled Trial
Authors: Preti Rony Carlos , Vasquez Ramirez Lisa Mariel , Ribeiro Monteiro Mário Luiz , Pelayes David E. , Takahashi Walter Yukihiko
Published: May 2013

Purpose: To compare the efficacy of therapy with panretinal photocoagulation (PRP) and intravitreal bevacizumab (IVB) injections versus PRP alone in patients with high-risk proliferative diabetic retinopathy (HR-PDR) with a 6-month follow-up. Methods: Forty-two patients with HR-PDR were prospectively studied in a randomised, masked, controlled trial. Both eyes of each patient were randomised either to the study group (SG) receiving PRP plus IVB injections or the control group (CG) receiving PRP alone. Mean change in visual acuity (VA), optical coherence tomography-measured foveal thickness (FT) and macular volume (MV) were compared. Results: Intergroup comparisons showed no significant difference in VA while FT exhibited a significant (p < 0.05) difference at 1 month of follow-up and MV was significantly reduced at the 1- and 3-month follow-up. Compared to baseline, VA was significantly worse at all follow-ups in the CG and was stable in the SG. FT increased significantly in the CG from baseline to the 1- and 6-month follow-ups and in the SG, no significant difference was observed. MV was significantly increased in the CG during all follow-up periods. Conclusion: In HR-PDR, using IVB injections as adjuvant treatment to PRP reduces the VA deterioration and results in decreased FT and MV measurements compared to PRP alone.
Tolerogenic Dendritic Cells: Key Regulators of Peripheral Tolerance in Health and Disease
Authors: Saei Azad , Hadjati Jamshid
Published: May 2013

Dendritic cells (DCs) as professional antigen-presenting cells are able to induce immunity and tolerance in different conditions, which leads to strong immune responses against hostile agents or tolerance to self-antigens. Although for subsets of DCs, a regulatory function has been shown, the role of the microenvironment is momentous to generate tolerogenic DCs (tDCs). Different microorganisms and tumor cells escape from immune responses by producing mediators and components that influence DCs to show tolerogenic characteristics. In this review, tDC induction was explained in steady state and disease conditions. Moreover, an overview was presented on the efforts to generate in vitro tDCs, their clinical applications and the problems which remain to be solved in this field.
Surgical Approach to the Management of Medullary Thyroid Cancer: When Is Lymph Node Dissection Needed?
Authors: Stamatakos Michael , Paraskeva Panoraia , Katsaronis Paraskevas , Tasiopoulou Georgia , Kontzoglou Konstantinos
Published: May 2013

Objective: Medullary thyroid cancer (MTC) is a rare and particularly aggressive type of thyroid cancer of neuroendocrine origin. It occurs in hereditary and sporadic forms and its aggressiveness is related to the clinical presentation and the type of RET mutation. Methods: In this article, we present the criteria, as reviewed in contemporary literature, regarding lymph node dissection and radical neck dissection in patients with either sporadic or hereditary MTC. Results: Early diagnosis and treatment remains the key to a 100% cure rate. Conclusions: Routine central lymph node dissection is the minimum procedure recommended for all sporadic and hereditary MTCs. Routine lateral lymph node dissection on either side is necessary when lymph node metastases are found in the central neck compartment.
Sudden Cardiac Death With Autopsy Findings of Uncertain Significance
Authors: Papadakis Michael , Raju Hariharan , Behr Elijah R. , De Noronha Sofia V. , Spath Nicholas , Kouloubinis Alexandros , Sheppard Mary N. , Sharma Sanjay
Published: May 2013

Background—

The sudden death of young individuals is commonly attributed to inherited cardiac disorders, and familial evaluation is advocated. The identification of pathognomonic histopathologic findings, or the absence of cardiac pathology (sudden arrhythmic death syndrome [SADS]) at postmortem, directs familial evaluation targeting structural disorders or primary arrhythmogenic syndromes, respectively. In a proportion of autopsies, structural abnormalities of uncertain significance are reported. We explored the hypothesis that such sudden cardiac deaths represent SADS.

Methods and Results—

Families (n=340) of index cases of sudden cardiac deaths who underwent postmortem evaluation were evaluated in specialist cardiogenetics clinics. Families in whom the deceased exhibited structural abnormalities of uncertain significance (n=41), such as ventricular hypertrophy, myocardial fibrosis, and minor coronary artery disease, were included in the study. Results were compared with 163 families with normal postmortem (SADS). Relatives underwent comprehensive cardiac evaluation. Twenty-one families (51%) with autopsy findings of uncertain significance received a diagnosis based on the identification of an inherited cardiac condition phenotype in ≥1 relatives: 14 Brugada syndrome; 4 long-QT syndrome; 1 catecholaminergic polymorphic ventricular tachycardia; and 2 cardiomyopathy. A similar proportion of families (47.2%) received a diagnosis in the SADS cohort (
P
=0.727). An arrhythmogenic syndrome was the predominant diagnosis in both cohorts (46% versus 45%;
P
=0.863).

Conclusions—

Familial evaluation after sudden cardiac deaths with autopsy findings of uncertain significance identified a similar proportion of primary arrhythmogenic syndromes to a contemporary series of SADS. Our study highlights the need for accurate interpretation of autopsy findings to avoid erroneous diagnoses, with potentially devastating implications.
Relative Atrial Natriuretic Peptide Deficiency and Inadequate Renin and Angiotensin II Suppression in Obese Hypertensive Men
Authors: Asferg Camilla L. , Nielsen Søren J. , Andersen Ulrik B. , Linneberg Allan , Møller Daniel V. , Hedley Paula L. , Christiansen Michael , Goetze Jens P. , Esler Murray , Jeppesen Jørgen L.
Published: May 2013

Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin–angiotensin system in 63 obese hypertensive men (obeseHT: body mass index, ≥30.0 kg/m
2
; 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m
2
; 24-hour ambulatory blood pressure, <130/80 mm Hg), and in 27 lean normotensive men (leanNT: body mass index, 20.0–24.9 kg/m
2
; 24-hour ambulatory blood pressure, <130/80 mm Hg). All study subjects were medication free. As a surrogate estimate for dietary sodium intake, we measured sodium excretion in a 24-hour urine collection and we measured serum levels of midregional proatrial NP and plasma levels of renin and angiotensin II. The obese men had higher mean (±SD) urinary sodium excretion (obeseHT, 213.6±85.2 mmol; obeseNT, 233.0±70.0 mmol) than the lean normotensive men (leanNT, 155.5±51.7 mmol;
P
=0.003). ObeseHT had lower (median [interquartile range]) serum midregional proatrial NP levels (49.2 [37.3–64.7] pmol/L) than leanNT (69.3 [54.3–82.9] pmol/L;
P
=0.003), whereas obeseNT had midregional proatrial NP levels in between (54.1 [43.2–64.7] pmol/L); obeseNT had lower (median [interquartile range]) plasma levels of renin (5.0 [3.0–8.0] mIU/L versus 9.0 [4.0–18.0]) and angiotensin II (2.4 [1.5–3.5] pmol/L versus 4.2 [2.2–7.9]) than obeseHT (
P
≤0.049), whereas obeseHT had similar plasma levels of renin and angiotensin II as leanNT (
P
≥0.19). Thus, despite a high sodium intake and a high blood pressure, obese hypertensive men have a relative NP deficiency and an inadequate renin–angiotensin system suppression.
Monoamine Oxidases Are Mediators of Endothelial Dysfunction in the Mouse Aorta
Authors: Sturza Adrian , Leisegang Matthias S. , Babelova Andrea , Schröder Katrin , Benkhoff Sebastian , Loot Annemarieke E. , Fleming Ingrid , Schulz Rainer , Muntean Danina M. , Brandes Ralf P.
Published: May 2013

Monoamine oxidases (MAOs) generate H
2
O
2
as a by-product of their catalytic cycle. Whether MAOs are mediators of endothelial dysfunction is unknown and was determined here in the angiotensin II and lipopolysaccharide-models of vascular dysfunction in mice. Quantitative real-time polymerase chain reaction revealed that mouse aortas contain enzymes involved in catecholamine generation and MAO-A and MAO-B mRNA. MAO-A and -B proteins could be detected by Western blot not only in mouse aortas but also in human umbilical vein endothelial cells. Ex vivo incubation of mouse aorta with recombinant MAO-A increased H
2
O
2
formation and induced endothelial dysfunction that was attenuated by polyethylene glycol-catalase and MAO inhibitors. In vivo lipopolysaccharide (8 mg/kg IP overnight) or angiotensin II (1 mg/kg per day, 2 weeks, minipump) treatment induced vascular MAO-A and -B expressions and resulted in attenuated endothelium-dependent relaxation of the aorta in response to acetylcholine. MAO inhibitors reduced the lipopolysaccharide- and angiotensin II–induced aortic reactive oxygen species formation by 50% (ferrous oxidation xylenol orange assay) and partially normalized endothelium-dependent relaxation. MAO-A and MAO-B inhibitors had an additive effect; combined application completely restored endothelium-dependent relaxation. To determine how MAO-dependent H
2
O
2
formation induces endothelial dysfunction, cyclic GMP was measured. Histamine stimulation of human umbilical vein endothelial cells to activate endothelial NO synthase resulted in an increase in cyclic GMP, which was almost abrogated by MAO-A exposure. MAO inhibition prevented this effect, suggesting that MAO-induced H
2
O
2
formation is sufficient to attenuate endothelial NO release. Thus, MAO-A and MAO-B are both expressed in the mouse aorta, induced by in vivo lipopolysaccharide and angiotensin II treatment and contribute via the generation of H
2
O
2
to endothelial dysfunction in vascular disease models.
Subfornical Organ Mediates Sympathetic and Hemodynamic Responses to Blood-Borne Proinflammatory Cytokines
Authors: Wei Shun-Guang , Zhang Zhi-Hua , Beltz Terry G. , Yu Yang , Johnson Alan Kim , Felder Robert B.
Published: May 2013

Proinflammatory cytokines play an important role in regulating autonomic and cardiovascular function in hypertension and heart failure. Peripherally administered proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), act on the brain to increase blood pressure, heart rate, and sympathetic nerve activity. These molecules are too large to penetrate the blood–brain barrier, and so the mechanisms by which they elicit these responses remain unknown. We tested the hypothesis that the subfornical organ (SFO), a forebrain circumventricular organ that lacks a blood–brain barrier, plays a major role in mediating the sympathetic and hemodynamic responses to circulating proinflammatory cytokines. Intracarotid artery injection of TNF-α (200 ng) or IL-1β (200 ng) dramatically increased mean blood pressure, heart rate, and renal sympathetic nerve activity in rats with sham lesions of the SFO (SFO-s). These excitatory responses to intracarotid artery TNF-α and IL-1β were significantly attenuated in SFO-lesioned (SFO-x) rats. Similarly, the increases in mean blood pressure, heart rate, and renal sympathetic nerve activity in response to intravenous injections of TNF-α (500 ng) or IL-1β (500 ng) in SFO-s rats were significantly reduced in the SFO-x rats. Immunofluorescent staining revealed a dense distribution of the p55 TNF-α receptor and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, in the SFO. These data suggest that SFO is a predominant site in the brain at which circulating proinflammatory cytokines act to elicit cardiovascular and sympathetic responses.
New species of Macrophyllodromia (Blattaria, Blattellidae) from Ecuador and a key to males of the genus
Authors: VIDLIČKA ĽUBOMÍR
Published: May 2013

Representatives of the cockroach genus Macrophyllodromia are widely distributed in Central and South Americas. The genus involves 10 species, including one new species described here, that are divided into 3 species groups—splendida, amabile and maximiliani. Macrophyllodromia onorei sp. n. is described as the fourth species of this genus from Ecuador. A key is provided for males of all known species of Macrophyllodromia and a species distribution map is presented.
Description of Megistoleon thaumatopteryx sp. nov. with notes on the genus Megistoleon Navás (Neuroptera, Myrmeleontidae)
Authors: BADANO DAVIDE
Published: May 2013

A new African species of antlion, Megistoleon thaumatopteryx sp. nov., is described from Mozambique. The poorly known genus Megistoleon Navás, 1931 and the only other species currently attributed to it, M. ritsemae (van der Weele, 1907) are redescribed in order to provide a better comparison with the new taxon. These myrmeleontids are easily distin-guishable by means of an exclusive set of characters besides a striking appearance.
Three new species of Neozygina Dietrich & Dmitriev (Hemiptera, Cicadellidae, Typhlocybinae) from Argentina, with a key to South American species
Authors: CATALANO MARÍA INÉS , PARADELL SUSANA , DIETRICH CHRISTOPHER H.
Published: May 2013

Three new species of Neozygina Dietrich & Dmitriev are described from Argentina, N. apicalis sp. nov., N. bifurcata sp. nov. and N. spinula sp. nov. Detailed morphological descriptions and illustrations of the new species are provided, and a key to South American species of the genus is given.
A new species of small tree frog, genus Dendropsophus (Anura: Hylidae) from the eastern Amazon lowlands of Ecuador
Authors: ORTEGA-ANDRADE H. MAURICIO , RON SANTIAGO R.
Published: May 2013

We describe a new species of the hylid frog genus Dendropsophus from Amazonian Ecuador. The new species, Dendrop-sophus shiwiarum sp. nov., appears to be part of the D. microcephalus species group. Dendropsophus shiwiarum differs from its congeners by a combination of: (1) tympanic membrane non-differentiated and annulus evident only ventrally, (2) disc of Finger III and Toe IV with pointed tip, (3) dorsal surfaces of digital discs with a conical tubercle as result of projection of distal phalanx, and (4) small size (SVL < 19 mm). The new species is morphologically most similar to Den-dropsophus riveroi. Examination of the type material of the latter suggests that some Ecuadorian populations reported as D. riveroi were misidentified and in fact belong to D. shiwiarum sp. nov.
Analysis of the Establishment of Seedlings of Açai (Euterpe Oleracea Mart.) in the Understory of a Forest of Amazon Floodplain
Authors: Cunha Freire Antonio Sérgio , Vitorino Maria Isabel , Gonçalves Jardim Mário Augusto , Leão de Sousa Adriano Marlison , Quaresma Adriano Costa , Gomes de Oliveira Fábio , Pereira Rafael do Nascimento
Published: May 2013

The effects of diffuse solar radiation (DSR), precipitation, and air temperature on survival and mortality of seedlings of açai (Euterpe oleracea Mart.) were evaluated in an estuarine floodplain forest located in the environmental protection area of Combu Island, Belém, Pará, Brazil, in the period from April 2010 to January 2011. An automatic weather station was installed in the understory of Combu Island to collect from the elements, whose location was defined by taking into account the sheer number of seedlings of açai and the incidence of diffuse radiation through canopy sunflecks on the solar panel. Six plots of 2 m × 20 m were demarcated and divided into 10 subplots of 2 m × 2 m in the directions of north, south, east, and west and two others at random around the station. The seedlings with a height between 10 cm and 2 m were quantified and monitored biweekly for survival and mortality. Data were statistically analyzed by a Pearson correlation. Initially, 1072 individuals were recorded, with a significant survival rate of 764 (71.3%) and a mortality rate of 308 (28.7%); therefore, a positive correlation between precipitation and survival was seen, while DSR directly influenced the mortality in the months of May–July 2010, mainly in continuous days of radiation above 34.56 MJ m−2 day−1.
Antipsychotic polypharmacy and high-dose prescription in schizophrenia: a 5-year comparison
Authors: Roh Daeyoung , Chang Jhin-Goo , Kim Chan-Hyung , Cho Hyun-Sang , An Suk Kyoon , Jung Young-Chul
Published: May 2013

Objective:

The co-prescription of multiple antipsychotic drugs continues to increase despite a lack of evidence supporting this practice. The purpose of this study was to quantify and describe recent trends of antipsychotic polypharmacy in Korean schizophrenic inpatients by comparing prescribed medications between the years of 2005 and 2010.

Methods:

We reviewed comprehensive medication profiles of schizophrenic patients discharged from a university psychiatric hospital in 2005 ( n=194) or 2010 ( n=201). Antipsychotic polypharmacy was defined as the concurrent receipt of two or more chemically distinct antipsychotics for at least 14 days. High antipsychotic dose was defined as a prescribed daily dose to defined daily dose ratio of greater than 1.5.

Results:

Antipsychotic polypharmacy increased between 2005 (37.1%) and 2010 (48.3%, p=0.025). The most frequently used drug within combinations of antipsychotics was haloperidol in 2005 (51.4%) and quetiapine in 2010 (48.5%). Overall, no changes were observed between 2005 and 2010 in the rate of prescribing high-dose antipsychotics. High-dose antipsychotic monotherapy decreased across years (from 30.4 to 18.4%), but high-dose antipsychotic polypharmacy increased (from 34.0 to 45.3%). Regression analysis revealed that antipsychotic polypharmacy was strongly associated with high doses of prescribed antipsychotics (odds ratio=18.60, p<0.001).

Conclusions:

The practice of prescribing multiple antipsychotics to patients with schizophrenia is increasing, and high-dose antipsychotic drugs are more likely to be prescribed in combination than in isolation. The reasons for this pattern of prescription and its impact warrants further study.
Deliberate Practice Improves Pediatric Residents’ Skills and Team Behaviors During Simulated Neonatal Resuscitation
Authors: Cordero Leandro , Hart Brandon J. , Hardin Rene , Mahan John D. , Nankervis Craig A.
Published: May 2013

Objective. To evaluate the skills and team behavior of pediatric residents during resuscitation with a high-fidelity mannequin before and after a deliberate practice intervention. Methods. Each month residents participate in two 90-minute videorecorded sessions (2-3 weeks apart) in an “off-site” delivery room during their neonatal ICU rotation. Teams responded to a scenario that required 5 skills (positive pressure ventilation, chest compressions, endotracheal intubation, umbilical vein catheterization, and epinephrine administration). Skills were scored for technique and timeliness and team behaviors for communication, management, and leadership. A 2-hour focused intervention was given between sessions. Results. In all, 33 residents (11 teams) completed the sessions. Gaps in procedural skills noted during the first session were corrected. Timeliness for completion of skills remained below expectations. Improvements in team behaviors were noted. Conclusions. Deliberate practice improved procedural skills and team performance. Lack of improvement in timeliness suggests that a different educational paradigm is required.
Factors Affecting Subspecialty Referrals by Pediatric Primary Care Providers for Children With Obesity-Related Comorbidities
Authors: Walsh Carolyn O. , Milliren Carly E. , Feldman Henry A. , Taveras Elsie M.
Published: May 2013

Objective. To determine referral patterns from pediatric primary care to subspecialists for overweight/obesity and related comorbidities. Methods. We used the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey to identify overweight/obesity and 5 related comorbidities in primary care visits between 2005 and 2009 by children 6 to 18 years. The primary outcome was whether the visit ended in referral. We used multivariable analysis to examine factors associated with referral. Results. We identified 34 225 database visits. A total of 17.1% were with overweight (body mass index = 85th to 94th percentile) or obese (body mass index ≥ 95th percentile) patients. A total of 7.1% of primary care visits with overweight/obese children ended in referral. Referral was more likely when obesity was the reason for visit (odds ratio = 2.83; 95% confidence interval = 1.61-4.97) but was not associated with presence of a comorbidity (odds ratio = 1.35; 95% confidence interval = 0.75-2.44). Conclusions. Most overweight or obese children are not referred, regardless of comorbidity status. One reason may be low levels of appropriate diagnosis.