bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructure of Placenta of Gravidas with Gestational Diabetes Mellitus
Authors: Meng Qian , Shao Li , Luo Xiucui , Mu Yingping , Xu Wen , Gao Chao , Gao Li , Liu Jiayin , Cui Yugui
Published: August 2015

Objectives. Gestational diabetes mellitus (GDM) leads to an abnormal placental environment which may cause some structural alterations of placenta and affect placental development and function. In this study, the ultrastructural appearances of term placentas from women with GDM and normal pregnancy were meticulously compared.Materials and Methods. The placenta tissues of term birth from 10 women with GDM and 10 women with normal pregnancy were applied with the signed informed consent. The morphology of fetomaternal interface of placenta was examined using light microscopy (LM) and transmission electron microscopy (TEM).Results. On LM, the following morphological changes in villous tissues were found in the GDM placentas when compared with the control placentas: edematous stroma, apparent increase in the number of syncytial knots, and perivillous fibrin deposition. On TEM, the distinct ultrastructural alterations indicating the degeneration of terminal villi were found in the GDM placentas as follows: thickening of the basal membrane (BM) of vasculosyncytial membrane (VSM) and the VSM itself, significantly fewer or even absent syncytiotrophoblastic microvilli, swollen or completely destroyed mitochondria and endoplasmic reticulum, and syncytiotrophoblasts with multiple vacuoles.Conclusion. Ultrastructural differences exist between GDM and control placentas. The differences of placenta ultrastructure are likely responsible for the impairment of placental barrier and function in GDM.
A Modern Syllogistic Method in Intuitionistic Fuzzy Logic with Realistic Tautology
Authors: Rushdi Ali Muhammad , Zarouan Mohamed , Alshehri Taleb Mansour , Rushdi Muhammad Ali
Published: August 2015

The Modern Syllogistic Method (MSM) of propositional logic ferrets out from a set of premises all that can be concluded from it in the most compact form. The MSM combines the premises into a single function equated to 1 and then produces the complete product of this function. Two fuzzy versions of MSM are developed in Ordinary Fuzzy Logic (OFL) and in Intuitionistic Fuzzy Logic (IFL) with these logics augmented by the concept of Realistic Fuzzy Tautology (RFT) which is a variable whose truth exceeds 0.5. The paper formally proves each of the steps needed in the conversion of the ordinary MSM into a fuzzy one. The proofs rely mainly on the successful replacement of logic 1 (or ordinary tautology) by an RFT. An improved version of Blake‐Tison algorithm for generating the complete product of a logical function is also presented and shown to be applicable to both crisp and fuzzy versions of the MSM. The fuzzy MSM methodology is illustrated by three specific examples, which delineate differences with the crisp MSM, address the question of validity values of consequences, tackle the problem of inconsistency when it arises, and demonstrate the utility of the concept of Realistic Fuzzy Tautology.
Sinus of Valsalva Aneurysm: A Rare Cause of Dyspnea
Authors: Smer Aiman , Elsallabi Osama , Ayan Mohamed , Buaisha Haitam , Rayes Hamza , Alshebani Yazeid , Tantoush Hamza , Salih Mohsin
Published: August 2015

Sinus of Valsalva aneurysm (SOVA) is a rare clinical entity. Clinical manifestations can vary from an incidental finding on an imaging study to a life-threatening emergency. We report a case of a 51-year-old female with a large symptomatic left SOVA. Echocardiogram and computed tomography angiography (CTA) of the chest revealed marked dilatation of the left sinus of Valsalva, measuring 7.5 cm. This resulted in superior displacement of the left main coronary artery. Surgical repair of the aneurysm with reimplantation of the right and left coronary arteries was performed in addition to aortic valve replacement (Bentall procedure). The patient had an uneventful postoperative course and remains asymptomatic at the three-month follow-up visit.
The Okhotsk-Japan Circulation Pattern and the Heavy Rainfall in Beijing in 2012 Summer
Authors: Wang Yafei , Qin Jianzhao , Zhu Lijuan
Published: August 2015

Using station precipitation and reanalysis data, we examined the evolution of the large-scale circulations associated with the heavy rainfall event that occurred around July 21, 2012 (721 heavy rainfall). This study focuses on a role that the large-scale circulations named “the Okhotsk-Japan (OKJ) circulation pattern” played in causing the heavy rainfall case. We found that the 721 heavy rainfall occurred under a background of the OKJ circulation that persisted for about 10 days. However, the pattern was different from the normal OKJ circulation, for this circulation pattern accompanied a blocking high between the Ural Mountains and the Baikal Lake. This difference resulted from the seasonal change of the basic flow. The related Rossby wave propagated eastward during the persisting period of the dominated OKJ pattern. This caused the development of a low-pressure system around the Baikal Lake and the weakening of a ridge around the Okhotsk Sea. The slow evolution of the OKJ circulation created a favorable environment for the moisture transport to northern China, assisting in the generation of the 721 heavy rainfall.
Gamma-Ray Bursts as Multienergy Neutrino Sources
Authors: Asano Katsuaki , Murase Kohta
Published: August 2015

We review theoretical models for nonelectromagnetic emission, mainly neutrinos and cosmic rays, from gamma-ray bursts (GRBs). In various stages of the relativistic jet propagation, cosmic-ray ion acceleration and subsequent neutrino emission are expected. GRBs are popular candidate sources of the highest-energy cosmic rays, and their prompt phase has been most widely discussed. IceCube nondetection of PeV neutrinos coincident with GRBs has put interesting constraints on the standard theoretical prediction. The GRB-UHECR hypothesis can critically be tested by future observations. We also emphasize the importance of searches for GeV-TeV neutrinos, which are expected in the precursor/orphan or prompt phase, and lower-energy neutrinos would be more guaranteed and their detections even allow us to probe physics inside a progenitor star. Not only classical GRBs but also low-power GRBs and transrelativistic supernovae can be promising sources of TeV-PeV neutrinos, and we briefly discuss implications for the cumulative neutrino background discovered by IceCube.
Utilizing the Updated Gamma-Ray Bursts and Type Ia Supernovae to Constrain the Cardassian Expansion Model and Dark Energy
Authors: Wei Jun-Jie , Ma Qing-Bo , Wu Xue-Feng
Published: August 2015

We update gamma-ray burst (GRB) luminosity relations among certain spectral and light-curve features with 139 GRBs. The distance modulus of 82 GRBs atz>1.4can be calibrated with the sample atz≤1.4by using the cubic spline interpolation method from the Union2.1 Type Ia supernovae (SNe Ia) set. We investigate the joint constraints on the Cardassian expansion model and dark energy with 580 Union2.1 SNe Ia sample(z<1.4)and 82 calibrated GRBs’ data(1.4<z≤8.2). In ΛCDM, we find that adding 82 high-zGRBs to 580 SNe Ia significantly improves the constraint onΩm-ΩΛplane. In the Cardassian expansion model, the best fit isΩm=0.24-0.15+0.15andn=0.16-0.52+0.30  (1σ), which is consistent with the ΛCDM cosmology(n=0)in the1σconfidence region. We also discuss two dark energy models in which the equation of statew(z)is parameterized asw(z)=w0andw(z)=w0+w1z/(1+z), respectively. Based on our analysis, we see that our universe at higher redshift up toz=8.2is consistent with the concordance model within1σconfidence level.
Primary Murine Myotubes as a Model for Investigating Muscular Dystrophy
Authors: Smolina Natalia , Kostareva Anna , Bruton Joseph , Karpushev Alexey , Sjoberg Gunnar , Sejersen Thomas
Published: August 2015

Muscular dystrophies caused by defects in various genes are often associated with impairment of calcium homeostasis. Studies of calcium currents are hampered because of the lack of a robust cellular model. Primary murine myotubes, formed upon satellite cell fusion, were examined for their utilization as a model of adult skeletal muscle. We enzymatically isolated satellite cells and induced them to differentiation to myotubes. Myotubes displayed morphological and physiological properties resembling adult muscle fibers. Desmin and myosin heavy chain immunoreactivity in the differentiated myotubes were similar to the mature muscle cross-striated pattern. The myotubes responded to electrical and chemical stimulations with sarcoplasmic reticulum calcium release. Presence of L-type calcium channels in the myotubes sarcolemma was confirmed via whole-cell patch-clamp technique. To assess the use of myotubes for studying functional mutation effects lentiviral transduction was applied. Satellite cells easily underwent transduction and were able to retain a positive expression of lentivirally encoded GFP up to and after the formation of myotubes, without changes in their physiological and morphological properties. Thus, we conclude that murine myotubes may serve as a fruitful cell model for investigating calcium homeostasis in muscular dystrophy and the effects of gene modifications can be assessed due to lentiviral transduction.
Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy
Authors: Sciandra Francesca , Bigotti Maria Giulia , Giardina Bruno , Bozzi Manuela , Brancaccio Andrea
Published: August 2015

In skeletal muscle, dystroglycan (DG) is the central component of the dystrophin-glycoprotein complex (DGC), a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1) have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others) model systems that have been developed with the aim of directly engineeringDAG1in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy.
Study of Posterior Cerebral Artery in Human Cadaveric Brain
Authors: Gunnal S. A. , Farooqui M. S. , Wabale R. N.
Published: August 2015

Objective. Basilar artery (BA) terminates in right and left posterior cerebral arteries (PCAs). Each PCA supplies respective occipital lobe of the cerebrum. The present study is designed to know the morphology, morphometry, branching pattern, and symmetry of PCA. Methods. The study included 340 PCAs dissected from 170 human cadaveric brains. Results. Morphological variations of P1 segment included, aplasia (2.35%), hypoplasia (5.29%), duplication (2.35%), fenestration (1.17%), and common trunk shared with SCA (1.76%). Morphological variations of origin of P2 segment included direct origin of it from BA (1.17%) and ICA (2.35%). Unusually, two P2 segments, each arising separately from BA and ICA, were observed in 1.17%. Unilateral two P2 segments from CW were found in 0.58%. Morphological variations of course of P2 were duplication (0.58%), fenestration (0.58%), and aneurysm (1.76%). Unilateral P2 either adult or fetal was seen in 4.71%. The group II branching pattern was found to be most common. Asymmetry of P2 was 40%. Morphometry of P2 revealed mean length of 52 mm and mean diameter of 2.7 mm. Conclusion. The present study provides the complete anatomical description of PCA regarding morphology, morphometry, symmetry, and its branching pattern. Awareness of these variations is likely to be useful in cerebrovascular procedures.
Uric Acid Levels in Normotensive Children of Hypertensive Parents
Authors: Yildirim Ali , Keles Fatma , Kosger Pelin , Ozdemir Gokmen , Ucar Birsen , Kilic Zubeyir
Published: August 2015

This study evaluated uric acid concentrations in normotensive children of parents with hypertension. Eighty normotensive children from families with and without a history of essential hypertension were included. Concentrations of lipid parameters and uric acid were compared. Demographic and anthropometric characteristics were similar in the groups. Systolic and diastolic blood pressure were higher in the normotensive children of parents with hypertension without statistically significant difference (P>0.05). Uric acid concentrations were higher in the normotensive children of parents with hypertension (4.61 versus 3.57 mg/dL,P<0.01). Total cholesterol and triglyceride concentrations were similar in the two groups. Systolic and diastolic blood pressure were significantly higher in control children aged >10 years (P<0.01). Uric acid levels were significantly higher in all children with more pronounced difference after age 10 of years (P<0.001). Positive correlations were found between the level of serum uric acid and age, body weight, body mass index, and systolic and diastolic blood pressure in the normotensive children of parents. The higher uric acid levels in the normotensive children of hypertensive parents suggest that uric acid may be a predeterminant of hypertension. Monitoring of uric acid levels in these children may allow for prevention or earlier treatment of future hypertension.
Information-Theoretical Quantifier of Brain Rhythm Based on Data-Driven Multiscale Representation
Authors: Choi Young-Seok
Published: August 2015

This paper presents a data-driven multiscale entropy measure to reveal the scale dependent information quantity of electroencephalogram (EEG) recordings. This work is motivated by the previous observations on the nonlinear and nonstationary nature of EEG over multiple time scales. Here, a new framework of entropy measures considering changing dynamics over multiple oscillatory scales is presented. First, to deal with nonstationarity over multiple scales, EEG recording is decomposed by applying the empirical mode decomposition (EMD) which is known to be effective for extracting the constituent narrowband components without a predetermined basis. Following calculation of Renyi entropy of the probability distributions of the intrinsic mode functions extracted by EMD leads to a data-driven multiscale Renyi entropy. To validate the performance of the proposed entropy measure, actual EEG recordings from ratsn=9experiencing 7 min cardiac arrest followed by resuscitation were analyzed. Simulation and experimental results demonstrate that the use of the multiscale Renyi entropy leads to better discriminative capability of the injury levels and improved correlations with the neurological deficit evaluation after 72 hours after cardiac arrest, thus suggesting an effective diagnostic and prognostic tool.

Corrigendum to “Information-Theoretical Quantifier of Brain Rhythm Based on Data-Driven Multiscale Representation”
Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats
Authors: Hales Jena B. , Ocampo Amber C. , Broadbent Nicola J. , Clark Robert E.
Published: August 2015

Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion.
Nonlinear Stability of the Triangular Libration Points for Radiating and Oblate Primaries in CR3BP in Nonresonance Condition
Authors: Singh Nutan , Narayan A.
Published: August 2015

This paper investigates the existence of resonance and nonlinear stability of the triangular equilibrium points when both oblate primaries are luminous. The study is carried out near the resonance frequency, satisfying the conditionsω1=ω2,  ω1=2ω2, andω1=3ω2in circular cases by the application of Kolmogorov-Arnold-Moser (KAM) theory. The study is carried out for the various values of radiation pressure and oblateness parameters in general. It is noticed that the system experiences resonance atω1=2ω2,  ω1=3ω2for different values of radiation pressures and oblateness parameter. The caseω1=ω2corresponds to the boundary region of the stability for the system. It is found that, except for some values of the radiation pressure, and oblateness parameters and forμ≤μc=0.0385209, the triangular equilibrium points are stable.
Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets
Authors: Ullah Majeed , Ullah Hanif , Murtaza Ghulam , Mahmood Qaisar , Hussain Izhar
Published: August 2015

The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.
Systemic Inflammation in Duchenne Muscular Dystrophy: Association with Muscle Function and Nutritional Status
Authors: Cruz-Guzmán Oriana del Rocío , Rodríguez-Cruz Maricela , Escobar Cedillo Rosa Elena
Published: August 2015

Inflammation described in patients with Duchenne muscular dystrophy (DMD) may be related to loss of muscle function or to obesity. It is unknown if circulating proinflammatory cytokines (IL-6, IL-1, and TNF-α) levels are associated with muscle function. The purpose was to evaluate whether an association exists between systemic inflammation with muscle function and nutritional status in DMD patients. In 66 DMD patients without corticosteroid treatment, the following were evaluated in serum: cytokines (IL-1, IL-6, and TNF-α), C-reactive protein (CRP), leptin, adiponectin, and creatine kinase (CK). Muscle function was evaluated using Vignos Scale. Patients with better muscle function had the highest concentration of CK, IL-1, and TNF-αcompared with less muscle function. No differences in IL-6 and adiponectin concentration were identified among groups with different levels of muscle function. Also, no differences were observed in the concentration of cytokines among groups with different nutritional status levels (underweight, normal weight, and overweight/obese). However, CRP and leptin were increased in the obese group compared with normal and underweight subjects. Systemic inflammation is increased in patients with better muscle function and decreases in DMD patients with poorer muscle function; nevertheless, systemic inflammation is similar among different levels of nutritional status in DMD patients.
Provider Perspectives on the Influence of Family on Nursing Home Resident Transfers to the Emergency Department: Crises at the End of Life
Authors: Stephens Caroline , Halifax Elizabeth , Bui Nhat , Lee Sei J. , Harrington Charlene , Shim Janet , Ritchie Christine
Published: August 2015

Background. Nursing home (NH) residents often experience burdensome and unnecessary care transitions, especially towards the end of life. This paper explores provider perspectives on the role that families play in the decision to transfer NH residents to the emergency department (ED).Methods. Multiple stakeholder focus groups (n=35participants) were conducted with NH nurses, NH physicians, nurse practitioners, physician assistants, NH administrators, ED nurses, ED physicians, and a hospitalist. Stakeholders described experiences and challenges with NH resident transfers to the ED. Focus group interviews were recorded and transcribed verbatim. Transcripts and field notes were analyzed using a Grounded Theory approach.Findings. Providers perceive that families often play a significant role in ED transfer decisions as they frequently react to a resident change of condition as a crisis. This sense of crisis is driven by 4 main influences: insecurities with NH care; families being unprepared for end of life; absent/inadequate advance care planning; and lack of communication and agreement within families regarding goals of care.Conclusions. Suboptimal communication and lack of access to appropriate and timely palliative care support and expertise in the NH setting may contribute to frequent ED transfers.
Systemic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Zhengqing Fengtongning Combined with Methotrexate in Rheumatoid Arthritis
Authors: Chen Xiu-min , Huang Run-yue , Huang Qing-chun , Chu Yong-liang , Yan Jing-yao
Published: August 2015

Chinese medicines are gaining wider acceptance. They have been used for treating rheumatoid arthritis (RA) for thousands of years, and the need to investigate the interaction between Chinese medicines and western medicines is widely recognized. In this study, a large number of RCTs and CCTs were analyzed to systematically assess the effects and adverse events of Zhengqing Fengtongning (ZQFTN) for RA. Eleven studies that contained 956 participants (508 in the treatment group; 448 in the control group) were included. The results showed that although ZQFTN combined with methotrexate MTX could not decrease the swollen joint count and tender joint count of RA patients better than MTX alone, the combination therapy might relieve the duration of morning stiffness (SMD: −16.06; 95% CI: −28.77 to −3.34), reduce laboratory indexes (RF: SMD: −10.84; 95% CI: −19.39 to −2.29; ESR: SMD: −7.26; 95% CI: −11.54 to −2.99; CRP: SMD: −3.66; 95% CI: −5.94 to −1.38), and improve the overall effect (RR: 1.08; CI: 1.01 to 1.16) better than monotherapy. The combination therapy was significantly better in controlling adverse drug reactions (RR: 0.60; 95% CI: 0.46 to 0.79). Through this systematic review, we found that ZQFTN combined with MTX for the treatment of RA might have better clinical efficacy than MTX only and might be superior in terms of controlling adverse drug reactions.
Postoperative Complications of Beger Procedure
Authors: Samejima Peternelli Nayana , Wajsfeld Tali , Henrique Yazawa Santos Felipe , Schmidt de Azevedo Otavio , Altenfelder Silva Rodrigo , Monteiro Pacheco Junior Adhemar
Published: August 2015

Introduction. Chronic pancreatitis (CP) is considered an inflammatory disease that may cause varying degrees of pancreatic dysfunction. Conservative and surgical treatment options are available depending on dysfunction severity.Presentation of Case. A 36-year-old male with history of heavy alcohol consumption and diagnosed CP underwent a duodenal-preserving pancreatic head resection (DPPHR or Beger procedure) after conservative treatment failure. Refractory pain was reported on follow-up three months after surgery and postoperative imaging uncovered stones within the main pancreatic duct and intestinal dilation. The patient was subsequently subjected to another surgical procedure and intraoperative findings included protein plugs within the main pancreatic duct and pancreaticojejunal anastomosis stricture. A V-shaped enlargement and main pancreatic duct dilation in addition to the reconstruction of the previous pancreaticojejunal anastomosis were performed. The patient recovered with no further postoperative complications in the follow-up at an outpatient clinic.Discussion. Main duct and pancreaticojejunal strictures are an unusual complication of the Beger procedure but were identified intraoperatively as the cause of patient’s refractory pain and explained intraductal protein plugs accumulation.Conclusion. Patients that undergo Beger procedures should receive close outpatient clinical follow-up in order to guarantee postoperative conservative treatment success and therefore guarantee an early detection of postoperative complications.
Recent Advances in General Game Playing
Authors: Świechowski Maciej , Park HyunSoo , Mańdziuk Jacek , Kim Kyung-Joong
Published: August 2015

The goal of General Game Playing (GGP) has been to develop computer programs that can perform well across various game types. It is natural for human game players to transfer knowledge from games they already know how to play to other similar games. GGP research attempts to design systems that work well across different game types, including unknown new games. In this review, we present a survey of recent advances (2011 to 2014) in GGP for both traditional games and video games. It is notable that research on GGP has been expanding into modern video games. Monte‐Carlo Tree Search and its enhancements have been the most influential techniques in GGP for both research domains. Additionally, international competitions have become important events that promote and increase GGP research. Recently, a video GGP competition was launched. In this survey, we review recent progress in the most challenging research areas of Artificial Intelligence (AI) related to universal game playing.
Microwave-Induced Structural and Functional Injury of Hippocampal and PC12 Cells Is Accompanied by Abnormal Changes in the NMDAR-PSD95-CaMKII Pathway
Authors: Wang Li-Feng , Wei Li , Qiao Si-Mo , Gao Xiao-Na , Gao Ya-Bing , Wang Shui-Ming , Zhao Li , Dong Ji , Xu Xin-Ping , Zhou Hong-Mei , Hu Xiang-Jun , Peng Rui-Yun
Published: August 2015

Recent studies have highlighted the important role of the postsynaptic NMDAR-PSD95-CaMKII pathway for synaptic transmission and related neuronal injury. Here, we tested changes in the components of this pathway upon microwave-induced neuronal structure and function impairments. Ultrastructural and functional changes were induced in hippocampal neurons of rats and in PC12 cells exposed to microwave radiation. We detected abnormal protein and mRNA expression, as well as posttranslational modifications in the NMDAR-PSD95-CaMKII pathway and its associated components, such as synapsin I, following microwave radiation exposure of rats and PC12 cells. Thus, microwave radiation may induce neuronal injury via changes in the molecular organization of postsynaptic density and modulation of the biochemical cascade that potentiates synaptic transmission.
Investigation of miR9-1, miR9-2 and miR9-3 Methylation in Hodgkin Lymphoma
Authors: Ben Dhiab Myriam , Ziadi Sonia , Louhichi Teheni , Ben Gacem Riadh , Ksiaa Feryel , Trimeche Mounir
Published: August 2015

Background: miR9 is an important tumor suppressor microRNA regulated by DNA methylation in various types of cancers. Methods: We analyzed the methylation status of the 3 members of the miR9 family in 58 cases of Hodgkin lymphoma (HL) in comparison to 15 reactive lymph nodes. We also assessed the relationships between miR9 methylation and Epstein-Barr virus (EBV) infection and several clinicopathological parameters. Results: We found that 84.5% of HL cases had a methylation in at least 1 of the 3 loci of miR9, whereas none of the nontumoral samples was methylated. The highest rate of methylation was found in miR9-2 (5q14.3) in 74.1% of the HL cases, followed by miR9-3 (15q26.1) in 56.9% and miR9-1 (1q22) in only 8.6% (p < 0.001). The promoter methylation of miR9-3 was more frequent in patients older than 15 years than in children (p = 0.02) and among women rather than men (p = 0.02). However, no significant correlation was found between miR9 methylation and EBV infection. Conclusion: These results indicate that miR9 methylation, especially miR9-2, is a frequent event in HL and may be involved in HL pathogenesis, irrespective of EBV infection.
Quality of Life in Patients Suffering from Active Exudative Age-Related Macular Degeneration: The EQUADE Study
Authors: Matamoros Emilie , Maurel Frédérique , Léon Nadia , Solomiac Agnès , Bardoulat Isabelle , Joubert Marc , Hermans Martine , Moser Eric , Le Picard Serge , Souied Eric H. , Leveziel Nicolas
Published: August 2015

Purpose: Age-related macular degeneration (AMD) is the main cause of visual loss in the elderly population. With the use of anti-vascular endothelial growth factor, the visual outcomes of exudative AMD patients have been improved. This study was aimed at assessing the quality of life (QoL) of exudative AMD patients treated with ranibizumab and at determining its drivers in a real-life setting. Methods: We performed a national, cross-sectional, observational survey based on questionnaires sent to members of French associations relative to AMD between December 2012 and March 2013. Patients suffering from exudative AMD with at least one intravitreal injection of ranibizumab within the last 6 months were included. Demographics, AMD characteristics, visual acuity (VA) and past and ongoing treatments were collected. The 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was self-administered. A multivariate model was used to identify QoL drivers. Results: 416 questionnaires fulfilled the complete criteria for both QoL and cost analyses. The mean age of exudative AMD patients was 78.0 years and bilateral involvement was reported in 60.4%. The overall mean QoL score was 53.4. Mental health, driving and role difficulties were the most widely affected domains. After bivariate analyses, long-term illness status, worse VA and higher number of unpaid aids were associated with worse QoL, with odds ratios of 2.4, 5.2 and 11.6, respectively. The mean cost per year and per patient was 1,741 EUR. The main components of costs were aids and services and the purchase of visual equipment. Conclusions: The main predictors of QoL in exudative AMD patients treated with ranibizumab are VA outcomes, home healthcare and social services provided to the patients.
Infection-Related Hospitalizations in Home Hemodialysis Patients
Authors: Bi Shu-Hong , Tang Wen , Rigodanzo-Massey Nives , Young Bessie A. , Blagg Christopher R. , Wang Tao , Ahmad Suhail
Published: August 2015

Introduction and Aims: Infection is an important cause of hospitalization and death in patients receiving hemodialysis (HD). Few studies have examined infection-related hospitalizations in home HD (HHD) population. The purpose of this study was to examine the scope of infections and the effect of HHD modality (daily home HD (DHD) and conventional home HD (CHD)) on infection-related hospitalizations in HHD patients. Methods: The study was performed in a large cohort of HHD patients. Infection-related hospitalizations during July 1, 2005, and August 30, 2010, were abstracted from the centralized computer system. Data on demographics, dialysis vintage and dialysis modality were analyzed. Results: One hundred sixty-five patients were included. During a median follow-up of 5 years, infection-related hospitalizations were observed in approximately 35.8% of all hospitalizations, which was the first cause for hospitalization. Rates of non-access-related infections were observed to be higher than that of access-related infections (1.7:1). Rates (per 100 person-years) of soft-tissue infection, pneumonia and sepsis ranged from 0.85 to 1.82 in patients on HHD. Meanwhile, access-related infection was the main cause for access-related hospitalizations (34.8%). Cox regression analysis showed that the usage of different dialysis modalities was not associated with a high risk for infection-related hospitalizations in HHD patients. Conclusions: Infection-related hospitalization occurred frequently in HHD patients. A broad range of infections, many unrelated to dialysis access, resulted in hospitalization in this population. HHD modalities were not associated with infection-related hospitalizations in HHD patients. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=433517.
Epstein-Barr Virus-Associated Gastric Carcinoma: Use of Host Cell Machineries and Somatic Gene Mutations
Authors: Abe Hiroyuki , Kaneda Atsushi , Fukayama Masashi
Published: August 2015

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct subtype of gastric carcinoma, consisting of clonal growth of EBV-infected epithelial cells. Its unique characteristics have been demonstrated by epidemiological, clinical and pathological studies using in situ hybridization for EBV-encoded small RNAs. An oncogenic process for EBVaGC has also been revealed. EBV uses various host-cell machineries, including cell division machinery to propagate clonal virus genomes, DNA-methylation machinery to epigenetically control infected cells, and microRNA and exosome machineries to modify the behavior and microenvironment of infected cells. Recent comprehensive molecular analyses from The Cancer Genome Atlas project demonstrate that EBVaGC is a representative molecular subtype that is distinct from microsatellite unstable, genomically stable and chromosome unstable subtypes. In addition to having the highest level of DNA methylation in CpG islands of promoter regions, EBVaGC harbors particular gene alterations, including a high frequency of mutations in PIK3CA and ARID1A, mutation in BCOR, and amplification of PD-L1 and PD-L2. Although currently undetermined, the virus might use the altered cellular functions that are induced by these somatic mutations. Further investigation of virus-driven oncogenesis will enable hitherto unknown functions of stomach epithelial cell machineries to be elucidated, which may reveal potential therapeutic targets for EBVaGC.
Performance of the 16-Item Informant Questionnaire on Cognitive Decline for the Elderly (IQCODE) in an Arabic-Speaking Older Population
Authors: Phung Thien Kieu Thi , Chaaya Monique , Asmar Khalil , Atweh Samir , Ghusn Husam , Khoury Rose Mary , Prince Martin , Waldemar Gunhild
Published: August 2015

Background/Aim: The North African and Middle Eastern region has high illiteracy rates among older people, making direct cognitive testing challenging. Validated screening instruments for dementia in Arabic are lacking. We aimed to validate the Arabic version of the 16-item Informant Questionnaire on Cognitive Decline for the Elderly (A-IQCODE 16) for screening for dementia through an informant. Methods: 236 Lebanese participants older than 65 years, 143 with normal cognition and 93 with mild-to-moderate dementia according to the DSM-IV criteria, and their informants were recruited. Half of the participants had no formal education. Interviewers blinded to the cognitive status of the participants administered the A-IQCODE 16 to the informants. The ability of the A-IQCODE 16 to screen for dementia was evaluated against the DSM-IV diagnoses. Results: The A-IQCODE 16 had excellent overall predictive power (area under the receiver operator characteristic curve = 0.96). A cutoff point of >3.34 yielded the best sensitivity (92.5%) and specificity (94.4%) for dementia screening. At this cutoff point, the discriminatory ability of the A-IQCODE 16 was comparable between participants with and those without formal education. Conclusion: The A-IQCODE 16 is not biased by education and is therefore useful as a brief screening tool for dementia among Arabic-speaking older adults with low education.
Transitional Changes in Cerebral Blood Volume at Birth
Authors: Schwaberger Bernhard , Pichler Gerhard , Binder-Heschl Corinna , Baik Nariae , Avian Alexander , Urlesberger Berndt
Published: August 2015

Background: Near-infrared spectroscopy (NIRS) enables non-invasive measurements of changes in the concentration of oxygenated (ΔHbO2) and reduced (ΔHbR) haemoglobin. Changes in total haemoglobin (ΔHbT = ΔHbO2 + ΔHbR) provide information on changes in cerebral blood volume (CBV). Objective: The aim was to evaluate the behaviour of CBV during immediate postnatal transition in term infants. Design: This observational study was conducted at the Medical University of Graz. NIRS measurements were carried out in term infants without need for respiratory support by using ‘NIRO 200-NX' (Hamamatsu) over the first 15 min after birth. Results: 109 infants with a mean gestational age of 38 + 6 weeks (±7 days) and birth weight of 3,242 g (±481) were included. Related to a reference value at minute 15, a significant decrease of HbT was observed for each minute within the study period. The mean (±SD) decrease of HbT of 17 (±40) µmol/l from minutes 2 to 15 represents a decrease of CBV of 1.0 ml/100 g brain (±2.2). Conclusions: In healthy newborns, CBV decreased over the whole study period. This likely reflects a physiological process. The impact and clinical relevance of different CBV behaviour during immediate transition needs to be investigated in further studies.
Unsuspected Ganglioneuroma of the Choroid Diagnosed after Enucleation
Authors: Mbagwu Michael , Rahmani Bahram , Srivastava Arth , Burrowes Delilah , Bryar Paul J.
Published: August 2015

We report a case of an unsuspected ganglioneuroma of the choroid in a patient with neurofibromatosis type 1. A 5-year-old girl presented from an outside institution with right proptosis and glaucoma since birth. Magnetic resonance imaging was obtained and showed a cavernous sinus mass extending into the right orbit and multiple orbital lesions. Additionally, increased signal in the posterior globe of the right eye was noted, but its etiology was unclear at the time. She was lost to follow-up for 3 years and later returned with a blind painful eye. Enucleation was performed, and histopathology was significant for diffuse choroidal ganglioneuroma and advanced glaucoma. We report the atypical history, examination findings, and histopathology to support the diagnosis.
Differentiating Glomerular Inflammation from Fibrosis in a Bone Marrow Chimera for Rat Anti-Glomerular Basement Membrane Glomerulonephritis
Authors: Zhou Cindy , Lou Kristie , Tatum Kiana , Funk Jeremiah , Wu Jean , Bartkowiak Todd , Kagan David , Lou Yahuan
Published: August 2015

Background: Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end-stage disease. This study investigated how these 2 phases were controlled. Methods: Using a rat anti-glomerular basement membrane GN model, we established bone marrow (BM) chimeras between GN-resistant Lewis (LEW) and GN-susceptible Wistar Kyoto (WKY) rats. Glomerular inflammation and fibrosis were compared between chimeras. Results: LEW's BM to WKY chimeras with or without co-transfer of host WKY's T cells were GN-resistant. On the other hand, WKY's BM to LEW (LEWWKY) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEWWKY chimeras were similar to those in immunized WKY rats at their inflammatory peak. Thus, glomerular inflammation was controlled by BM-derived non-T cell populations. However, unlike WKY rats, LEWWKY rats did not develop fibrosis until the end of experiments (84 days) in spite of persistent inflammation and albuminuria. Conclusion: Inflammation alone was not sufficient to trigger fibrosis, suggesting a critical role of glomerular cells in the fibrotic process. As LEWWKY chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation.
Expression of Cell Membrane Antigens in Cells Excreted in the Urinary Sediment Predicts Progression of Renal Disease in Patients with Focal Segmental Glomerulosclerosis
Authors: Konieczny Andrzej , Czyżewska-Buczyńska Agnieszka , Ryba Monika , Rukasz Dagna , Krajewska Magdalena , Witkiewicz Wojciech , Hruby Zbigniew
Published: August 2015

Background/Aims: A link between the number of podocytes excreted in the urine and activity of glomerular disease has been established. The aim of this study was to investigate possible correlations between urinary cells' phenotype and the progression of focal segmental glomerulosclerosis (FSGS). Methods: Forty patients with newly diagnosed FSGS were included. Cells were isolated from urine by adherence to collagen-coated cover slips and assessed for the expression of podocalyxin (PDX), CD68 and Ki67 antigens by indirect immunofluorescence. In addition, double-staining procedures were performed in combinations of the above antigens plus cytokeratin, WT1 and CD-105. Twenty-two patients in whom urinary protein to creatinine ratio exceeded 2.0 at diagnosis were followed for 36 months, with assessments of renal function and proteinuria every 3 months. During observation, patients were subjected to standard therapy. Results: Significantly higher numbers of Ki67 positive cells at the onset of the study were observed in patients who have doubled serum creatinine (SCr) in follow-up, than in those who have not (p = 0.0149). By logistic regression analysis, both CD68 and Ki67, but not anti-PDX positive cell numbers at diagnosis were found to be predictors of doubling SCr concentration in 36 months' follow-up. Results of double staining indicate that PDX positive cells could be identified as podocytes or their precursors and parietal epithelial cells. Conclusion: Urinary sediment PDX positive cell numbers do not predict the progression of FSGS, whereas CD68 and Ki67 phenotype of urinary podocytic lineage clearly has a prognostic significance in 36 months' observation of primary FSGS.
Altered Gene Expression Profiles of the Hypothalamic Arcuate Nucleus of Male Mice Suggest Profound Developmental Changes in Peptidergic Signaling
Authors: Molnár Csilla S. , Sárvári Miklós , Vastagh Csaba , Maurnyi Csilla , Fekete Csaba , Liposits Zsolt , Hrabovszky Erik
Published: August 2015

Neuropeptides of the hypothalamic arcuate nucleus (ARC) regulate important homeostatic and endocrine functions and also play critical roles in pubertal development. The altered peptidergic and aminoacidergic neurotransmission accompanying pubertal maturation of the ARC is not fully understood. Here we studied the developmental shift in the gene expression profile of the ARC of male mice. RNA samples for quantitative RT-PCR studies were isolated from the ARC of 14-day-old infantile and 60-day-old adult male mice with laser capture microdissection. The expression of 18 neuropeptide, 15 neuropeptide receptor, 4 sex steroid receptor and 6 classic neurotransmitter marker mRNAs was compared between the two time points. The adult animals showed increased mRNA levels encoding cocaine- and amphetamine-regulated transcripts, galanin-like peptide, dynorphin, kisspeptin, proopiomelanocortin, proenkephalin and galanin and a reduced expression of mRNAs for pituitary adenylate cyclase-activating peptide, calcitonin gene-related peptide, neuropeptide Y, substance P, agouti-related protein, neurotensin and growth hormone-releasing hormone. From the neuropeptide receptors tested, melanocortin receptor-4 showed the most striking increase (5-fold). Melanocortin receptor-3 and the Y1 and Y5 neuropeptide Y receptors increased 1.5- to 1.8-fold, whereas δ-opioid receptor and neurotensin receptor-1 transcripts were reduced by 27 and 21%, respectively. Androgen receptor, progesterone receptor and α-estrogen receptor transcripts increased by 54-72%. The mRNAs of glutamic acid decarboxylases-65 and -67, vesicular GABA transporter and choline acetyltransferase remained unchanged. Tyrosine hydroxylase mRNA increased by 44%, whereas type-2 vesicular glutamate transporter mRNA decreased by 43% by adulthood. Many of the developmental changes we revealed in this study suggest a reduced inhibitory and/or enhanced excitatory neuropeptidergic drive on fertility in adult animals.
Poststroke Inflammasome Expression and Regulation in the Peri-Infarct Area by Gonadal Steroids after Transient Focal Ischemia in the Rat Brain
Authors: Lammerding Leoni , Slowik Alexander , Johann Sonja , Beyer Cordian , Zendedel Adib
Published: August 2015

CNS ischemia results in locally confined and rapid tissue damage accompanied by a loss of neurons and their circuits. Early and time-delayed inflammatory responses are critical variables determining the extent of neural disintegration and regeneration. Inflammasomes are vital effectors in innate immunity. Their activation in brain-intrinsic immune cells contributes to ischemia-related brain damage. The steroids 17β-estradiol (E2) and progesterone (P) are neuroprotective and anti-inflammatory. Using a transient focal rat ischemic model, we evaluated the time response of different inflammasomes in the peri-infarct zone from the early to late phases after poststroke ischemia. We show that the different inflammasome complexes reveal a specific time-oriented sequential expression pattern with a maximum at approximately 24 h after the infarct. Within the limits of antibody availability, immunofluorescence labeling demonstrated that microglia and neurons are major sources of the locally activated inflammasomes NOD-like receptor protein-3 (NLRP3) and associated speck-like protein (ASC), respectively. E2 and P given for 24 h immediately after ischemia onset reduced hypoxia-induced mRNA expression of the inflammasomes NLRC4, AIM2 and ASC, and decreased the protein levels of ASC and NLRP3. In addition, mRNA protein levels of the cytokines interleukin-1β (IL1β), IL18 and TNFα were reduced by the steroids. The findings provide for the first time a detailed flow chart of hypoxia-driven inflammasome regulation in the peri-infarct cerebral cortex. Further, we demonstrate that E2 and P alleviate the expression of certain inflammasome components, sometimes in a hormone-specific way. Besides directly regulating other cellular neuroprotective pathways, the control of inflammasomes by these steroids might contribute to its neuroprotective potency.