bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Multiexon Skipping Antisense Oligonucleotide Therapy for Duchenne Muscular Dystrophy
Authors: Aoki Yoshitsugu , Yokota Toshifumi , Wood Matthew J. A.
Published: July 2013

Duchenne muscular dystrophy (DMD) is an incurable, X-linked progressive muscle degenerative disorder that results from the absence of dystrophin protein and leads to premature death in affected individuals due to respiratory and/or cardiac failure typically by age of 30. Very recently the exciting prospect of an effective oligonucleotide therapy has emerged which restores dystrophin protein expression to affected tissues in DMD patients with highly promising data from a series of clinical trials. This therapeutic approach is highly mutation specific and thus is personalised. Therefore DMD has emerged as a model genetic disorder for understanding and overcoming of the challenges of developing personalised genetic medicines. One of the greatest weaknesses of the current oligonucleotide approach is that it is a mutation-specific therapy. To address this limitation, we have recently demonstrated that exons 45–55 skipping therapy has the potential to treat clusters of mutations that cause DMD, which could significantly reduce the number of compounds that would need to be developed in order to successfully treat all DMD patients. Here we discuss and review the latest preclinical work in this area as well as a variety of accompanying issues, including efficacy and potential toxicity of antisense oligonucleotides, prior to human clinical trials.
PLUGAM: Plug-In-Based Adaptation Middleware for Network Layer Protocols for Vehicular Ad Hoc Networks
Authors: Caloca Carlos F. , García-Macías J. Antonio , Delot Thierry
Published: July 2013

Vehicular communication environments are characterized by highly mobile nodes, frequent topology changes, and a great variation in the number of neighbor vehicles. The network layer (NL) protocols must adapt continuously to these unreliable conditions, hence the growing effort in the development of protocols specific to vehicular networks. The aim of this work is to help create vehicular systems with an adaptive network layer, by means of proposing a middleware based on an adaptation model and using as input the context information of the vehicle. The architecture will build an adaptive network layer using two types of run-time adaptations: modification of NL protocol internal parameters and adaptations where a selection between NL protocols must be made. To assess the feasibility of our approach, we present two case study examples and present a first prototype. In addition, we briefly evaluate the adaptation presented in case study 1 via simulation, and we found that it produces 20% less control overhead. Furthermore, we present an analysis of the prototype performance to get a rough idea on the cost of using the middleware in the vehicular system; results show that it is feasible to implement the middleware in hardware similar to today's midrange smartphones.
Risk Perception and Its Foundation among Swedish Individuals Occupationally Exposed to Air Pollutants and Chemicals: A Comparison of 1975 and 2011
Authors: Schenk Linda
Published: July 2013

Although work environment conditions have improved much in the last decades, occupational exposures to chemicals and air pollutants still cause adverse health effects. The risk perception of occupational exposures to hazardous substances and the motivations for it have been investigated through a questionnaire study. These results have also been compared to previous studies performed by the largest trade union confederation in Sweden in 1975. In the current survey, 30% of the respondents believe to be at risk, 48% not, and 22% state to be unsure. The proportion of persons experiencing to be at risk due to exposures to chemicals or air pollution at work is unexpectedly similar to that of 1975. The explanations offered for the risk perception were in many cases vague and of a subjective nature, but again results are similar to those of 1975. References to more solid justifications such as performed exposure measurements or medical health checks are scarce, with the latter case being as scarce today as in 1975. There are only a few indications that a more systematic management of work environment issues has developed at Swedish workplaces; for instance, managers were more commonly stated as a source of information in 2011 than in 1975.
Optimized Periocular Template Selection for Human Recognition
Authors: Bakshi Sambit , Sa Pankaj K. , Majhi Banshidhar
Published: July 2013

A novel approach for selecting a rectangular template around periocular region optimally potential for human recognition is proposed. A comparatively larger template of periocular image than the optimal one can be slightly more potent for recognition, but the larger template heavily slows down the biometric system by making feature extraction computationally intensive and increasing the database size. A smaller template, on the contrary, cannot yield desirable recognition though the smaller template performs faster due to low computation for feature extraction. These two contradictory objectives (namely, (a) to minimize the size of periocular template and (b) to maximize the recognition through the template) are aimed to be optimized through the proposed research. This paper proposes four different approaches for dynamic optimal template selection from periocular region. The proposed methods are tested on publicly available unconstrained UBIRISv2 and FERET databases and satisfactory results have been achieved. Thus obtained template can be used for recognition of individuals in an organization and can be generalized to recognize every citizen of a nation.
Effects of Qigong Exercise on Fatigue, Anxiety, and Depressive Symptoms of Patients with Chronic Fatigue Syndrome-Like Illness: A Randomized Controlled Trial
Authors: Chan Jessie S. M. , Ho Rainbow T. H. , Wang Chong-wen , Yuen Lai Ping , Sham Jonathan S. T. , Chan Cecilia L. W.
Published: July 2013

Background. Anxiety/depressive symptoms are common in patients with chronic fatigue syndrome- (CFS-) like illness. Qigong as a modality of complementary and alternative therapy has been increasingly applied by patients with chronic illnesses, but little is known about the effect of Qigong on anxiety/depressive symptoms of the patients with CFS-like illness.Purpose. To investigate the effects of Qigong on fatigue, anxiety, and depressive symptoms in patients with CFS-illness.Methods. One hundred and thirty-seven participants who met the diagnostic criteria for CFS-like illness were randomly assigned to either an intervention group or a waitlist control group. Participants in the intervention group received 10 sessions of Qigong training twice a week for 5 consecutive weeks, followed by home-based practice for 12 weeks. Fatigue, anxiety, and depressive symptoms were assessed at baseline and postintervention.Results. Total fatigue score [F1,135=13.888,P<0.001], physical fatigue score [F1,135=20.852,P<0.001] and depression score [F1,135=9.918,P=0.002] were significantly improved and mental fatigue score [F1,135=3.902,P=0.050] was marginally significantly improved in the Qigong group compared to controls. The anxiety score was not significantly improved in the Qigong group.Conclusion. Qigong may not only reduce the fatigue symptoms, but also has antidepressive effect for patients with CFS-like illness. Trial registrationHKCTR-1200.
Epidemiology of Back Pain in Children and Youth Aged 10–19 from the Area of the Southeast of Poland
Authors: Kędra Agnieszka , Czaprowski Dariusz
Published: July 2013

Objective. The aim of this work was to define the prevalence of back pain in children and youth aged 10–19 from the southeast of Poland.Material and Methods. The cross-sectional study included 1089 students (547 girls and 542 boys) aged 10–19. The prevalence of back pain, its intensity, location, and situations in which it occurred were assessed with a questionnaire.Results. Among 1089 respondents, 830 (76.2%) admitted that they had experienced back pain at various frequencies within the year preceding the study. Back pain was located mainly in the lumbar segment (74.8%). Mild pains were dominant, which was declared by 44.7% of the respondents. Girls experienced back pain significantly more frequently than boys (52.2% versus 47.8%,P<0.05).Conclusions. The research revealed that back pain is a common phenomenon. The prevalence of back pain in children and youth living in southeast Poland is similar to the frequency of occurrence of such complaints occurring in peers in other countries. It seems significant to monitor the remaining regions of Poland in order to define the scale of the problem and to look for the risk factors of back pain in children and youth to undertake efficient prophylactic actions.
Seismic Vulnerability Assessment of a Historical Church: Limit Analysis and Nonlinear Finite Element Analysis
Authors: Castellazzi G. , Gentilini C. , Nobile L.
Published: July 2013

The seismic vulnerability of a historical Basilica church located in Italy is studied by means of limit analysis and nonlinear finite element (FE) analysis. Attention is posed to the failure mechanisms involving the façade of the church and its interaction with the lateral walls. In particular, the limit analysis and the nonlinear FE analysis provide an estimate of the load collapse multiplier of the failure mechanisms. Results obtained from both approaches are in agreement and can support the selection of possible retrofitting measures to decrease the vulnerability of the church under seismic loads.
Friction and Wear Properties of Cold Gas Dynamic Sprayed α-Al2O3-Al Composite Coatings
Authors: Wu Jie , Tao Yongshan , Jin Huazi , Li Ming , Xiong Tianying , Sun Chao
Published: July 2013

Different proportions of α-Al2O3 and pure Al powders were coated onto AZ91D magnesium alloy substrates by cold gas dynamic spray. The microstructure and morphologies of the coatings were observed by scanning electron microscope. The friction and wear properties were tested by a ball-on-disk wear tester. It was found that the interfaces between grains and substrates formed close boundaries. It is revealed that the composite coatings could increase the friction or wear properties of the coatings. It was observed that the wear of coatings was converted from adhesive wear into abrasive wear with α-Al2O3 particles increasing and that the adhesive wear accompanied with abrasive wear would increase the wear rate of coatings.
Fixed Points of Multivalued Nonself Almost Contractions
Authors: Alghamdi Maryam A. , Berinde Vasile , Shahzad Naseer
Published: July 2013

We consider multivalued nonself-weak contractions on convex metric spaces and establish the existence of a fixed point of such mappings. Presented theorem generalizes results of M. Berinde and V. Berinde (2007), Assad and Kirk (1972), and many others existing in the literature.
Elevated Cerebrospinal Fluid Neopterin Concentration Is Associated with Disease Severity in Acute Puumala Hantavirus Infection
Authors: Hautala Timo , Partanen Terhi , Sironen Tarja , Rajaniemi Saara-Mari , Hautala Nina , Vainio Olli , Vapalahti Olli , Kauma Heikki , Vaheri Antti
Published: July 2013

Nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) is the most common hemorrhagic fever with renal syndrome (HFRS) in Europe. The infection activates immunological mechanisms that contribute to the pathogenesis and characteristics of the illness. In this study we measured cerebrospinal fluid (CSF) neopterin concentration from 23 acute-phase NE patients. We collected data on kidney function, markers of tissue permeability, haemodynamic properties, blood cell count, length of hospitalisation, inflammatory parameters, and ophthalmological properties. The neopterin levels were elevated (>5.8 nmol/L) in 22 (96%) NE-patients (mean 45.8 nmol/L); these were especially high in patients with intrathecal PUUV-IgM production (mean 58.2 nmol/L,P=0.01) and those with elevated CSF protein concentrations (mean 63.6 nmol/L,P<0.05). We also observed a correlation between the neopterin and high plasma creatinine value (r=0.66,P=0.001), low blood thrombocyte count (r=-0.42,P<0.05), and markedly disturbed refractory properties of an eye (r=0.47,P<0.05). Length of hospitalisation correlated with the neopterin (r=0.42,P<0.05; male patientsr=0.69,P<0.01). Patients with signs of tissue oedema and increased permeability also had high neopterin concentrations. These results reinforce the view that PUUV-HFRS is a general infection that affects the central nervous system and the blood-brain barrier.
Recent Developments in the X-Ray Reflectivity Analysis for Rough Surfaces and Interfaces of Multilayered Thin Film Materials
Authors: Fujii Yoshikazu
Published: July 2013

X-ray reflectometry is a powerful tool for investigations on rough surface and interface structures of multilayered thin film materials. The X-ray reflectivity has been calculated based on the Parratt formalism, accounting for the effect of roughness by the theory of Nevot-Croce conventionally. However, in previous studies, the calculations of the X-ray reflectivity often show a strange effect where interference effects would increase at a rough surface. And estimated surface and interface roughnesses from the X-ray reflectivity measurements did not correspond to the TEM image observation results. The strange result had its origin in a used equation due to a serious mistake in which the Fresnel transmission coefficient in the reflectivity equation is increased at a rough interface because of a lack of consideration of diffuse scattering. In this review, a new accurate formalism that corrects this mistake is presented. The new accurate formalism derives an accurate analysis of the X-ray reflectivity from a multilayer surface of thin film materials, taking into account the effect of roughness-induced diffuse scattering. The calculated reflectivity by this accurate reflectivity equation should enable the structure of buried interfaces to be analyzed more accurately.
Role of the Plasma Membrane Transporter of Organic Cations OCT1 and Its Genetic Variants in Modern Liver Pharmacology
Authors: Lozano Elisa , Herraez Elisa , Briz Oscar , Robledo Virginia S. , Hernandez-Iglesias Jorge , Gonzalez-Hernandez Ana , Marin Jose J. G.
Published: July 2013

Changes in the uptake of many drugs by the target cells may dramatically affect the pharmacological response. Thus, downregulation ofSLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively. Moreover, the overall picture may be modified to a considerable extent by the preexistence or the appearance during the pathogenic process of genetic variants. Some rare OCT1 variants enhance transport activity, whereas other more frequent variants impair protein maturation, plasma membrane targeting or the function of this carrier, hence reducing intracellular active drug concentrations. Here, we review current knowledge of the role of OCT1 in modern liver pharmacology, which includes the use of cationic drugs to treat several diseases, some of them of great clinical relevance such as diabetes and primary liver cancer (cholangiocarcinoma and hepatocellular carcinoma). We conclude that modern pharmacology must consider the individual evaluation of OCT1 expression/function in the healthy liver and in the target tissue, particularly if this is a tumor, in order to predict the lack of response to cationic drugs and to be able to design individualized pharmacological treatments with the highest chances of success.
Heparan Sulfate and Heparanase as Modulators of Breast Cancer Progression
Authors: Gomes Angélica M. , Stelling Mariana P. , Pavão Mauro S. G.
Published: July 2013

Breast cancer is defined as a cancer originating in tissues of the breast, frequently in ducts and lobules. During the last 30 years, studies to understand the biology and to treat breast tumor improved patients’ survival rates. These studies have focused on genetic components involved in tumor progression and on tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are involved in cell signaling, adhesion, extracellular matrix assembly, and growth factors storage. As a central molecule, HSPG regulates cell behavior and tumor progression. HS accompanied by its glycosaminoglycan counterparts regulates tissue homeostasis and cancer development. These molecules present opposite effects according to tumor type or cancer model. Studies in this area may contribute to unveil glycosaminoglycan activities on cell dynamics during breast cancer exploring these polysaccharides as antitumor agents. Heparanase is a potent tumor modulator due to its protumorigenic, proangiogenic, and prometastatic activities. Several lines of evidence indicate that heparanase is upregulated in all human sarcomas and carcinomas. Heparanase seems to be related to several aspects regulating the potential of breast cancer metastasis. Due to its multiple roles, heparanase is seen as a target in cancer treatment. We will describe recent findings on the function of HSPGs and heparanase in breast cancer behavior and progression.
Study of the Effects of Changing Physiological Conditions on Dielectric Properties of Breast Tissues
Authors: Sabouni Abas , Hahn Camerin , Noghanian Sima , Sauter Edward , Weiland Tim
Published: July 2013

This paper addresses the changes in the physical characteristics (temperature and water/blood content) of breast tissue under different physiological conditions. We examined ex vivo specimens of breast tissue excised at the time of surgery to study the effects of physiological conditions on dielectric properties. We observed that the dielectric properties strongly depend on tissue physiological state. When the biological tissues undergo physiological changes, such as those due to disease or those induced by external changes such as variations in the environmental temperature, the microscopic processes deviate from their normal state and impact the overall dielectric properties. This suggests that microwave imaging might be used to monitor the physiological conditions of the body.
Investigating the Relationship between Serum Level of s-Met (Soluble Hepatic Growth Factor Receptor) and Preeclampsia in the First and Second Trimesters of Pregnancy
Authors: Naghshvar Farshad , Torabizadeh Zhila , Moslemi Zadeh Narges , Mirbaha Hooman , Gheshlaghi Parand
Published: July 2013

Introduction. Preeclampsia (PE) is an important cause of mortality and morbidity for mothers, fetuses, and the newborns. Placenta plays a pivotal role in pathogenesis of PE. Hepatic growth factor (HGF) is a cytokine expressed by the mesenchymal stalk of placental villi during pregnancy and assumes a paracrine role in trophoblasts which express its receptor (c-MET). In the present study, we investigate the diagnostic value of s-Met (the soluble form of the receptor) in the first and second trimesters of pregnancy for early diagnosis of preeclampsia. Method and Materials. This is a case-control study conducted on 95 pregnant women. The serum level of s-Met was measured in the first and second trimesters, and the participants were followed until delivery. 44 individuals with preeclampsia (the case group) and 51 individuals without preeclampsia (the control group) were evaluated. Results. Serum level of s-Met in preeclamptic participants was lower than that of the control group in both the first and the second trimesters (P<0.0001). In addition, serum levels of s-Met were significantly lower during the first and second trimesters in patients with early, severe preeclampsia compared to those with late, mild preeclampsia (P<0.0001). The sensitivity and specificity of s-Met in the first and second trimesters were, respectively, (83%, 94%) and (77%, 94%) for early preeclampsia and (88%, 92%) and (86%, 98%) for severe preeclampsia. Conclusion. Considering our findings, serum level of s-Met may be used as a predictive factor for early detection of preeclampsia. Further research is required to corroborate the functional and therapeutic value of s-Met in preeclampsia.
Meningitis-Retention Syndrome as a Presentation of West Nile Virus Meningitis
Authors: Mankongpaisarnrung Charoen , Laengvejkal Pavis , Argueta Erwin , Limsuwat Chok , Sutamtewagul Grerk , Nugent Kenneth
Published: July 2013

A 26-year-old previously healthy man presented with fever, urinary retention, nuchal rigidity, and hyperreflexia but with a clear sensorium. His initial spinal fluid results were consistent with aseptic meningitis from West Nile virus infection, and this was confirmed by serological studies on blood and cerebrospinal fluid. Computed tomography and magnetic resonance imaging studies were unremarkable. He received supportive care and urinary catheterization to prevent bladder injury from overdistension. He was discharged home without recurrence of urinary retention after five days of hospitalization. Therefore, this case report describes the first case of West Nile virus meningitis in a patient with the meningitis-retention syndrome.
Oral Naftopidil Suppresses Human Renal-Cell Carcinoma by Inducing G1 Cell-Cycle Arrest in Tumor and Vascular Endothelial Cells
Authors: Iwamoto Yoichi , Ishii Kenichiro , Sasaki Takeshi , Kato Manabu , Kanda Hideki , Yamada Yasushi , Arima Kiminobu , Shiraishi Taizo , Sugimura Yoshiki
Published: July 2013

Renal cell carcinoma (RCC) is an angiogenesis-dependent and hypoxia-driven malignancy. As a result, several targeting agents are being investigated. However, the efficacy of current regimens is generally insufficient for their toxicity and poor overall response rates. We have recently reported that naftopidil exerts growth-inhibitory effects on human prostate cancer cells. In this study, we investigated the biochemical mechanisms by which naftopidil produces growth-inhibitory and antiangiogenic effects on RCC. We first tested the effects of naftopidil on the proliferation of ACHN and Caki-2 RCC cells. Next, we set up a model simulating the tumor microenvironment, in which ACHN cells were grafted onto the renal capsule of mice. We then tested the effects of naftopidil on human umbilical vein endothelial cells' cell proliferation and Matrigel plug vascularization. Finally, to establish the antitumor activity of naftopidil on RCC, we tested the antitumor effects of naftopidil on excised tumor specimens from 20 patients with RCC that were grafted beneath the renal capsule of mice. Naftopidil showed similar in vitro growth-inhibitory effects on all cell lines. Fluorescence-activated cell sorting analysis revealed an increase in G1 cell-cycle arrest in all naftopidil-treated cell lines. In vivo tumorigenic studies showed a significant reduction of ACHN tumor weight, Ki-67 index, and microvessel density (MVD) in naftopidil-treated mice. Naftopidil attenuated neovascularization in an in vivo Matrigel plug assay. Studies in mouse xenograft models also showed a significant MVD reduction in naftopidil-treated excised human RCC. The growth-inhibitory effects of naftopidil suggest it may be a novel anticancer agent and a potential preventive option for RCC. Cancer Prev Res; 6(9); 1000–6. ©2013 AACR.
Physiological Arousal Deficits in Addicted Gamers Differ Based on Preferred Game Genre
Authors: Metcalf Olivia , Pammer Kristen
Published: July 2013

Background/Aims: There has been significant discussion surrounding the psychopathology of excessive gaming and whether it constitutes an addiction. The current study investigated physiological and subjective levels of arousal in gamers of two genres and the relationship between sensation seeking and gaming addiction. Methods: Heart rate (HR), blood pressure (BP) and skin conductance were recorded at baseline, during gaming for 15 min and after gaming in 30 massively multiplayer online role-playing game (MMORPG) and 30 first-person shooter (FPS) male gamers. Gamers were identified as addicted using the Addiction-Engagement Questionnaire. Sensation seeking was measured using the Arnett Inventory of Sensation Seeking. Results: Addicted MMORPG gamers (n = 16) displayed significant decreases in cardiovascular activity during gaming compared to baseline and showed significant increases after gaming. Addicted FPS gamers (n = 13) had significant increases in BP during gaming which decreased significantly after gaming. In comparison, non-addicted MMORPG gamers (n = 14) had significant decreases in HR during gaming, whereas BP in non-addicted MMORPG and FPS gamers (n = 17) increased during gaming and after gaming. There were no significant relationships between sensation seeking and addiction. Conclusion: There are physiological arousal deficits in addicted gamers, and these patterns differ according to the genre of game played.
Role of Interleukin-6, Its Receptor and Soluble gp130 in Chronic Lung Disease of Prematurity
Authors: Chakraborty Mallinath , McGreal Eamon P. , Davies Philip L. , Nowell Mari A. , Jones Simon , Kotecha Sailesh
Published: July 2013

Background: Interleukin-6 (IL-6) signalling involves the interplay between IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130). IL-6 activity is modulated by the soluble receptors to produce both pro- and anti-inflammatory effects in human diseases and animal models. The expression and functional activity of these molecules in lungs of preterm ventilated infants is unknown. Objectives: We investigated this pathway in preterm infants who were at risk of developing chronic lung disease of prematurity (CLD). Methods: Cytokines and soluble receptors were measured in bronchoalveolar lavage fluid (BALF) from ventilated preterm infants ≤32 weeks of gestation who did or did not develop CLD. B9 cells, which specifically proliferate to IL-6, were used to assess BALF IL-6 functional activity. Results: Inflammatory cells, IL-8 and monocyte chemotactic protein-1 were increased in BALF from the CLD group when compared to the No CLD group (p < 0.05). BALF IL-6 and sIL-6R were similar in both groups. In contrast, BALF sgp130 and sgp130/sIL-6R were greater in the CLD group when compared to the No CLD group (p = 0.01 and p = 0.02, respectively). However, the increased BALF sgp130 did not appear to modulate the BALF IL-6 functional activity. Conclusion: Lung inflammation was observed in the CLD group. Increased BALF sgp130 was noted in the CLD group but it did not appear to modulate the pulmonary IL-6 bioactivity. Further research is needed to investigate the potential modulatory activity of sgp130 in the preterm lung.
Concomitant High-Grade Prostatic Intraepithelial Neoplasia Is Associated with Good Prognosis Factors and Oncologic Outcome after Radical Prostatectomy
Authors: Ingels Alexandre , Ploussard Guillaume , Allory Yves , Abbou Claude , de la Taille Alexandre , Salomon Laurent
Published: July 2013

Objectives: To assess correlations between concomitant high-grade prostatic intraepithelial neoplasia (HGPIN), pathological features and oncologic outcomes after radical prostatectomy (RP). Material and Methods: We prospectively collected a single-institution database of 2,351 patients who underwent RP between 1998 and 2011. Results: 1,272 (54.1%) patients had HGPIN on specimens. The mean follow-up was 28 months. Presence of HGPIN was significantly associated with a favorable preoperative risk status and with pathological factors of poor prognosis in RP specimens. Patients without HGPIN had a worse biochemical recurrence-free survival compared with those with HGPIN in RP specimen (log-rank test: p = 0.015). The 3-year RFS rate was 73.9% for the HGPIN group versus 67.2%. The absence of HGPIN was also significantly correlated with the use of androgen deprivation treatment during the follow-up (p < 0.001). In Cox multivariate analysis, taking into account the other prognostic pathological factors, HGPIN was not an independent predictive factor for PSA failure (p = 0.868). Conclusion: HGPIN is associated with factors of good prognosis but fails to show independent significance when classical pathological prognostic factors are taken into account.
Prevalence of Atopy and Respiratory Allergic Diseases in the Elderly SAPALDIA Population
Authors: Wüthrich Brunello , Schmid-Grendelmeier Peter , Schindler Christian , Imboden Medea , Bircher Andreas , Zemp Elisabeth , Probst-Hensch Nicole ,   and the SAPALDIA Team
Published: July 2013

Background: Because of changing world demographics, the elderly population is steadily increasing. Few studies have assessed the prevalence of atopy and allergic diseases in elderly persons with objective measures. The aim of this paper is to describe the prevalence of atopy, self-reported allergic rhinitis and doctor's diagnosed asthma in persons over the age of 60 in Switzerland. Methods: The cross-sectional examination of the Swiss Study on Air Pollution and Health in Adults (SAPALDIA 1), performed in 1991, included 9,651 adults aged 18-60 years. In 2001-2002 the same subjects were invited for a follow-up examination (SAPALDIA 2). Serum samples collected at baseline and follow-up were tested for specific IgE sensitization with the Phadiatop® (Phadia, Uppsala, Sweden, now Thermo Fisher Scientific) assay containing a mixture of common respiratory allergens (grass, birch, mugwort, Parietaria and olive pollen, dog, cat, horse, Cladosporium herbarum, house dust mite and flour mite). Atopy was defined as a positive result in the Phadiatop test according to guidelines by the manufacturer. The prevalence rates of atopy, self-reported allergic rhinitis and doctor's diagnosed asthma were evaluated by sex and age group (≤60 or >60 years). Results: 7,667 subjects (men = 3,692/women = 3,975) participated in the follow-up by responding to a detailed questionnaire (80% of SAPALDIA 1 participants). Phadiatop results were available for 5,835 participants (men = 2,839/women = 2,996). Prevalence rates of atopy (Phadiatop positive) were 36.4% in men aged ≤60 years versus 26.2% in men aged >60 years and 30.6 and 18.1% in women, respectively (both p < 0.001). Prevalence rates of self-reported allergic rhinitis in subjects >60 years old were 13.0% for men and 15.4% for women (p = 0.12), and for doctor's diagnosed asthma 6.6% versus 7.6%, respectively (p = 0.40). Both rhinitis and asthma prevalences were higher in persons <60 years. The results were not sensitive to potential bias from nonparticipation at follow-up as demonstrated by imputation of sex- and age-specific allergic rhinitis and asthma among nonparticipants. Conclusions: According to our estimates, the prevalence of allergic rhinitis among persons aged between 60 and 70 years in Switzerland in the present cohort is of the order of 13-15% and should not be underestimated, although it is lower than in age groups ≤60 years.
Preauricular Transmandibular and Transzygomatic Approach for Tumors of the Infratemporal Fossa Revisited
Authors: Timoshenko Andrei P. , Asanau Alexander , Gavid Marie , Colin Victor , Martin Christian , Prades Jean-Michel
Published: July 2013

Aim: To demonstrate the surgical technique and results in patients operated on with a preauricular transmandibular transzygomatic approach. Methods: This surgical technique was used in 21 patients with benign and malignant tumors of the infratemporal fossa (ITF), operated on between 1999 and 2011. Results: Twenty-one patients were enrolled in the study. There were 6 patients with benign tumors and 15 with malignant ones. No patients with benign lesions show any disease recurrence 5 years after surgery and present excellent functional and cosmetic results. Postoperatively, a reduction of pain was noted in all patients with malignant lesions. Four patients in this group, who are alive 5 years after surgery, do not demonstrate any disease progression. Conclusion: The described approach provides an excellent exposure of the ITF and could be the procedure of choice in the management of ITF tumors.
Estimating Sibling Recurrence Risk in Population Sample Surveys
Authors: Graubard Barry I. , Sirken Monroe G.
Published: July 2013

Background/Aims: Sibling recurrence risk (SRR) is a measure of familial aggregation of a disease and is often used in family-based studies in genetic epidemiology to indicate the existence of possible genes conferring susceptibility of disease. Estimating SRR requires information about the disease status of sibships of families with two or more siblings where at least one is affected. Since family-based studies are not usually random samples, estimates of SRR derived from these studies may be biased. Network sampling used in survey research offers a way to ascertain the disease status of sibships from interviewed individuals in household survey samples, in order to obtain (approximately) unbiased estimators of SRR and its related SRR ratio (SRR divided by the prevalence of disease). Methods: Two methods of ascertaining sibships of affected families are considered: in one method the siblings' affected status is reported by an individual, regardless of the individual's affected status, and in the other method only affected individuals can report their siblings' affected status. Network estimators of SRR and SRR ratio and estimators of their standard errors are provided. Results: Reported diabetes for siblings from the 1976 National Health Interview is used to illustrate the estimation methods. The SRR ratio for diabetes among living siblings was 5.79% [relative standard error (RSE) = 5.12%], and for living or deceased siblings, it was 7.66% (RSE = 3.76%). Conclusions: Network sampling estimators can provide population estimates of SRR and SRR ratio for diseases such as diabetes.
Allergenic Properties of Enzymatically Hydrolyzed Peanut Flour Extracts
Authors: Shi Xiaolei , Guo Rishu , White Brittany L. , Yancey Adrienne , Sanders Timothy H. , Davis Jack P. , Burks A. Wesley , Kulis Michael
Published: July 2013

Background: Peanut flour is a high-protein, low-oil, powdered material prepared from roasted peanut seed. In addition to being a well-established food ingredient, peanut flour is also the active ingredient in peanut oral immunotherapy trials. Enzymatic hydrolysis was evaluated as a processing strategy to generate hydrolysates from peanut flour with reduced allergenicity. Methods: Soluble fractions of 10% (w/v) light roasted peanut flour dispersions were hydrolyzed with the following proteases: Alcalase (pH 8.0, 60°C), pepsin (pH 2.0, 37°C) or Flavourzyme (pH 7.0, 50°C) for 60 min. Western blotting, inhibition ELISA and basophil activation tests were used to examine IgE reactivity. Results: Western blotting experiments revealed the hydrolysates retained IgE binding reactivity and these IgE-reactive peptides were primarily Ara h 2 fragments regardless of the protease tested. Inhibition ELISA assays demonstrated that each of the hydrolysates had decreased capacity to bind peanut-specific IgE compared with nonhydrolyzed controls. Basophil activation tests revealed that all hydrolysates were comparable (p > 0.05) to nonhydrolyzed controls in IgE cross-linking capacity. Conclusions: These results indicate that hydrolysis of peanut flour reduced IgE binding capacity; however, IgE cross-linking capacity during hydrolysis was retained, thus suggesting such hydrolysates are not hypoallergenic.
Human Unrestricted Somatic Stem Cell Administration Fails to Protect Nude Mice from Cisplatin-Induced Acute Kidney Injury
Authors: Gheisari Yousof , Ahmadbeigi Naser , Aghaee-Bakhtiari Seyed Hamid , Nassiri Seyed Mahdi , Amanpour Saeid , Azadmanesh Kayhan , Hajarizadeh Athena , Mobarra Zahra , Soleimani Masoud
Published: July 2013

Background: Kidney failure is a debilitating disorder with limited treatment options. The kidney-protective effects of stem cells have been vastly investigated and promising results have been achieved with various sources of stem cells. However, in spite of beneficial effects on other disease models, the renoprotective potential of human cord blood-derived unrestricted somatic stem cells (USSC) has not been examined so far. Methods: In the present study, acute kidney failure was induced in female nude mice and the effect of USSC transplantation on kidney function and structure was assessed. Furthermore, the expression of some cytokine genes was examined by real-time PCR. Homing of the transplanted cells into kidneys was assessed by flow cytometry, immunohistochemistry, and real-time PCR. Results: USSC-conditioned medium did not attenuate the in vitro nephrotoxic effects of cisplatin. Transplantation of USSC to nude mice did not protect kidney function and was associated with worsened kidney structural damage. USSC transplantation was also associated with a decline in the renal expression of VEGF-A gene. In spite of these effects, the transplanted cells could not be detected in the kidneys by any of the exploited methods and they were mainly entrapped in the lungs. Conclusion: These data indicate that USSC are not suitable for cell therapy in the setting of acute kidney injury. Also, this study shows that these stem cells are able to affect damaged kidneys even if they are not homed there.
Assessing the Impact of Population Stratification on Association Studies of Rare Variation
Authors: Jiang Yunxuan , Epstein Michael P. , Conneely Karen N.
Published: July 2013

Aims: The study of rare variants, which can potentially explain a great proportion of heritability, has emerged as an important topic in human gene mapping of complex diseases. Although several statistical methods have been developed to increase the power to detect disease-related rare variants, none of these methods address an important issue that often arises in genetic studies: false positives due to population stratification. Using simulations, we investigated the impact of population stratification on false-positive rates of rare-variant association tests. Methods: We simulated a series of case-control studies assuming various sample sizes and levels of population structure. Using such data, we examined the impact of population stratification on rare-variant collapsing and burden tests of rare variation. We further evaluated the ability of 2 existing methods (principal component analysis and genomic control) to correct for stratification in such rare-variant studies. Results: We found that population stratification can have a significant influence on studies of rare variants especially when the sample size is large and the population is severely stratified. Our results showed that principal component analysis performed quite well in most situations, while genomic control often yielded conservative results. Conclusions: Our results imply that researchers need to carefully match cases and controls on ancestry in order to avoid false positives caused by population structure in studies of rare variants, particularly if genome-wide data are not available.
Comparison of Immunoglobulin E Measurements on IMMULITE and ImmunoCAP in Samples Consisting of Allergen-Specific Mouse-Human Chimeric Monoclonal Antibodies towards Allergen Extracts and Four Recombinant Allergens
Authors: Szecsi Pal B. , Stender Steen
Published: July 2013

Background: Specific immunoglobulin E (IgE) antibody in vitro tests are performed on enzyme immunoassay systems. Poor agreement among systems has been reported and comparisons have been made exclusively with allergen extracts - not with recombinant allergens. Here we compare the ImmunoCAP and the IMMULITE systems. Methods: Ten patient samples with positive IgE toward egg white, birch pollen or cat or dog dander were compared using allergen extracts or the recombinant allergens Gal d 1, Bet v 1, Fel d 1 and Can f 1 with the two assay systems. Comparisons were also performed using four monoclonal mouse-human chimeric IgE antibodies specific for the same allergenic components. Results: IMMULITE estimated a higher allergen-specific IgE concentration in sera than ImmunoCAP when testing with allergen extracts as well as recombinant allergens. The chimeric antibodies gave an equivalent response in the total IgE and specific IgE (sIgE) with an average ratio of 1.08 (range 0.9-1.3) on ImmunoCAP. In contrast, IMMULITE exhibited sIgE signals that were substantially higher than the summed level of IgE for all four chimeric antibodies (average ratio 2.96 and range 1.7-4.3). Conclusion: Comparison using chimeric antibodies allowed the evaluation of the true performance of the systems. ImmunoCAP measured total IgE and sIgE equally, whereas IMMULITE displayed higher sIgE signals when compared to the summed level of total IgE for all four chimeric antibodies. Results obtained with the two assay systems are not interchangeable by means of mathematical conversion.
An Analytical Comparison of the Principal Component Method and the Mixed Effects Model for Association Studies in the Presence of Cryptic Relatedness and Population Stratification
Authors: Wang Kai , Hu Xijian , Peng Yingwei
Published: July 2013

The principal component method and the mixed effects model represent two popular approaches to controlling for population structure and cryptic relatedness in genetic association studies. There are only a handful of studies comparing their performance. These studies are typically based on simulation studies and the results are therefore limited in their applicability. In this paper, we conduct an analytical comparison of these two approaches in the presence of cryptic relatedness and population structure in terms of their validity and efficiency. In the presence of cryptic relatedness, we show that both methods are valid, but the mixed effects model is more powerful for detecting association. In the presence of population structure, however, we show that both methods can be invalid. The biases and variances of the estimates from the two methods are compared. Examples and simulation studies are provided to demonstrate the conclusions.
The Ratio of Osteoprotegerin to Fetuin-A Is Independently Associated with Vascular Stiffness in Hemodialysis Patients
Authors: Kim Hye Ryoun , Kim Su-Hyun , Han Min-Ji , Yoon Yu-Sik , Oh Dong-Jin
Published: July 2013

Background: The aim of the present study was to compare levels of fetuin-A, osteoprotegerin (OPG), and heat shock protein (HSP)70 according to the stage of chronic kidney disease (CKD), as well as to evaluate the association between serum fetuin-A, OPG, and HSP70 concentrations with respect to vascular stiffness and calcification in hemodialysis (HD) patients. Methods: We measured fetuin-A, OPG, and HSP70 in 35 healthy controls, 35 patients with stage 3 CKD, 35 patients with stage 4 CKD, and 81 HD patients. Using these data, we studied the association of fetuin-A, OPG, and HSP70 with clinical, biochemical, and vascular measures in HD patients. Results: Levels of OPG and HSP70 were higher and fetuin-A was lower in HD patients than in healthy controls. The cardio-ankle vascular index (CAVI) showed a positive correlation with OPG (r = 0.248, p = 0.040) and the OPG/fetuin-A ratio (r = 0.260, p = 0.031). The ankle-brachial index (ABI) showed a negative correlation with OPG (r = -0.245, p = 0.031) and the OPG/fetuin-A ratio (r = -0.267, p = 0.018). Intima-media thickness (IMT) showed a positive correlation with OPG (r = 0.273, p = 0.014) and the OPG/fetuin-A ratio (r = 0.269, p = 0.015). On stepwise multiple linear regression analyses, only the logarithmic function of the OPG/fetuin-A ratio was independently associated with CAVI (β = 13.325, SE = 6.247, p = 0.038). Conclusions: Our results demonstrate that OPG and the OPG/fetuin-A ratio are correlated with increased vascular stiffness and IMT in HD patients. In addition, the OPG/fetuin-A ratio was independently associated with vascular stiffness in HD patients.
Obesity and Familial Predisposition Are Significant Determining Factors of an Adverse Metabolic Profile in Young Patients with Congenital Adrenal Hyperplasia
Authors: Moreira Ricardo P.P. , Villares Sandra M. , Madureira Guiomar , Mendonca Berenice B. , Bachega Tânia A.S.S.
Published: July 2013

Background/Aims: Glucocorticoid (GC) therapy is known to predispose to an adverse metabolic profile. Therefore, we investigated the prevalence of obesity and metabolic syndrome (MetS) in young patients with congenital adrenal hyperplasia (CAH) and to correlate this prevalence with GC treatment and family history. Methods: The study population consisted of 33 young CAH patients who received cortisone acetate during their growth periods; those who were salt wasters also received fludrocortisone. Obesity was defined by a body mass index (BMI) >95th percentile and MetS by the National Cholesterol Education Program Third Adult Treatment Panel modified criteria. Each patient's familial history of MetS components was assessed. The impact of GC therapy on the metabolic profile was analyzed by comparing CAH patients with BMI z-score-matched controls. Results: MetS and obesity were observed in 12.1 and 30.3% of the CAH patients, respectively, both of which were higher than in the reference population. A positive family history of MetS was found to be more prevalent in the obese patients compared with the nonobese CAH patients, and similar findings were observed for the controls. The metabolic profile did not differ between the CAH patients and matched subjects. Conclusion: CAH patients presented a higher prevalence of obesity and MetS, which were not correlated with the GC treatment. This study suggests that obesity and familial predisposition are significant determining factors for an adverse metabolic profile in CAH patients.
Severe Acute Rhabdomyolysis Induced by Multi-Agent Chemotherapy for Alveolar Rhabdomyosarcoma in a 15-Year-Old Female: A Case Report
Authors: Matsuzaki Hiroshi , Koga Yuhki , Suminoe Aiko , Oba Utako , Takimoto Tomohito , Hara Toshiro
Published: July 2013

This is the first paper to report the association of cancer chemotherapy with rhabdomyolysis in children. A previously healthy, 15-year-old Japanese female was diagnosed as having alveolar rhabdomyosarcoma. She received the first cycle of multi-agent chemotherapy without any adverse effects. However, she developed severe acute rhabdomyolysis shortly after the second cycle of multi-agent chemotherapy, which consisted of etoposide, ifosfamide, actinomycin-D and vincristine. Her condition deteriorated rapidly and she was treated with mechanical ventilation and fluid replacement. After further evaluation, anticancer drugs were thought to be responsible for the rhabdomyolysis.