bluuebunny/crossref_metadata_2025 huggingface dataset:
A Generic Decomposition Formula for Pricing Vanilla Options under Stochastic Volatility Models
Authors: Merino Raúl , Vives Josep
Published: June 2015

We obtain a decomposition of the call option price for a very general stochastic volatility diffusion model, extending a previous decomposition formula for the Heston model. We realize that a new term arises when the stock price does not follow an exponential model. The techniques used for this purpose are nonanticipative. In particular, we also see that equivalent results can be obtained by using Functional Itô Calculus. Using the same generalizing ideas, we also extend to nonexponential models the alternative call option price decomposition formula written in terms of the Malliavin derivative of the volatility process. Finally, we give a general expression for the derivative of the implied volatility under both the anticipative and the nonanticipative cases.
Efficacy of Laparoscopic Mini Gastric Bypass for Obesity and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Quan Yingjun , Huang Ao , Ye Min , Xu Ming , Zhuang Biao , Zhang Peng , Yu Bo , Min Zhijun
Published: June 2015

Background. Controversies on the utility of laparoscopic mini gastric bypass (LMGB) in weight loss and type 2 diabetes mellitus (T2DM) control still exist.Methods. We conducted a comprehensive literature search of PubMed, EMBASE, and Cochrane Library. Review Manager was used to perform the meta-analysis and the weighted mean difference (WMD) and/or odds ratio with 95% confidence interval (95% CI) were used to evaluate the overall size effect.Results. The literature search identified 16 studies for systematic review and 15 articles for meta-analysis. Compared with LAGB, LSG, and LRYGB, LMGB showed significant weight loss [WMD, −6.58 (95% CI, −9.37, −3.79),P<0.01(LAGB); 2.86 (95% CI, 1.40, 5.83),P=0.004(LSG); 10.33 (95% CI, 4.30, 16.36),P<0.01(LRYGB)] and comparable/higher T2DM remission results [86.2% versus 55.6%,P=0.06(LAGB); 89.1% versus 76.3%,P=0.004(LAGB); 93.4% versus 77.6%,P=0.006(LAGB)]; LMGB also had shorter learning curve and less operation time than LRYGB [WMD, −35.2 (95% CI, −46.94, −23.46)].Conclusions. LMGB appeared to be effective in weight loss and T2DM remission and noninferior to other bariatric surgeries. However, clinical utility of LMGB needs to be further validated by future prospective randomized controlled trials.
Heterogeneity of Systemic Oxidative Stress Profiles in COPD: A Potential Role of Gender
Authors: Maury Jonathan , Gouzi Farés , De Rigal Philippe , Heraud Nelly , Pincemail Joël , Molinari Nicolas , Pomiès Pascal , Laoudj-Chenivesse Dalila , Mercier Jacques , Préfaut Christian , Hayot Maurice
Published: June 2015

Oxidative stress (OS) plays a key role in the muscle impairment and exercise capacity of COPD patients. However, the literature reveals that systemic OS markers show great heterogeneity, which may hinder the prescription of effective antioxidant supplementation. This study therefore aimed to identify OS markers imbalance of COPD patients, relative to validated normal reference values, and to investigate the possibility of systemic OS profiles. We measured systemic enzymatic/nonenzymatic antioxidant and lipid peroxidation (LP) levels in 54 stable COPD patients referred for a rehabilitation program. The main systemic antioxidant deficits in these patients concerned vitamins and trace elements. Fully 89% of the COPD patients showed a systemic antioxidant imbalance which may have caused the elevated systemic LP levels in 69% of them. Interestingly, two patient profiles (clusters 3 and 4) had a more elevated increase in LP combined with increased copper and/or decreased vitamin C, GSH, and GPx. Further analysis revealed that the systemic LP level was higher in COPD women and associated with exercise capacity. Our present data therefore support future supplementations with antioxidant vitamins and trace elements to improve exercise capacity, but COPD patients will probably show different positive responses.
Small Bowel Obstruction due to Intestinal Xanthomatosis
Authors: Barrera-Herrera L. E. , Arias F. , Rodríguez-Urrego P. A. , Palau-Lázaro M. A.
Published: June 2015

Vast majority of bowel obstruction is due to postoperative adhesions, malignancy, intestinal inflammatory disease, and hernias; however, knowledge of other uncommon causes is critical to establish a prompt treatment and decrease mortality. Xanthomatosis is produced by accumulation of cholesterol-rich foamy macrophages. Intestinal xanthomatosis is an uncommon nonneoplastic lesion that may cause small bowel obstruction and several cases have been reported in the English literature as obstruction in the jejunum. We report a case of small intestinal xanthomatosis occurring in a 51-year-old female who presented with one day of copious vomiting and intermittent abdominal pain. Radiologic images revealed jejunal loop thickening and inflammatory changes suggestive of foreign body obstruction, diagnostic laparoscopy found two strictures at the jejunum, and a pathologic examination confirmed a segmental small bowel xanthomatosis. This case illustrates that obstruction even without predisposing factors such as hyperlipidemia or lymphoproliferative disorders.
Invertible Weighted Composition Operators on the Fock Space ofCN
Authors: Zhao Liankuo
Published: June 2015

We give a complete characterization of bounded invertible weighted composition operators on the Fock space ofCN.
Honey in the Prevention and Treatment of Infection in the CKD Population: A Narrative Review
Authors: Francis Anna , Cho Yeoungjee , Johnson David W.
Published: June 2015

Infection is a major cause of morbidity and mortality at all stages of chronic kidney disease (CKD). Multiresistant organisms are becoming increasingly common, particularly in the CKD population. Unfortunately, the rapid evolution of antibiotic resistance has not been mirrored by innovation in new antibiotic agents. Novel treatments are therefore urgently needed. Honey has garnered much interest due to its broad-spectrum antibacterial properties based on extensive experimental data. Unlike conventional antibiotics, honey has an added advantage as it appears to avoid inducing antimicrobial resistance in bacteria. This review discusses the potential mechanisms of action and role of honey in infection management in the general population, epidemiology and special challenges of infections in CKD populations, and the clinical trial evidence pertaining to the safety and efficacy of honey for the prevention and treatment of infections in CKD population.
Effects of Supervised Multimodal Exercise Interventions on Cancer-Related Fatigue: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Meneses-Echávez José Francisco , González-Jiménez Emilio , Ramírez-Vélez Robinson
Published: June 2015

Objective. Cancer-related fatigue (CRF) is the most common and devastating problem in cancer patients even after successful treatment. This study aimed to determine the effects of supervised multimodal exercise interventions on cancer-related fatigue through a systematic review and meta-analysis.Design. A systematic review was conducted to determine the effectiveness of multimodal exercise interventions on CRF. Databases of PubMed, CENTRAL, EMBASE, and OVID were searched between January and March 2014 to retrieve randomized controlled trials. Risk of bias was evaluated using the PEDro scale.Results. Nine studiesn=772were included in both systematic review and meta-analysis. Multimodal interventions including aerobic exercise, resistance training, and stretching improved CRF symptoms (SMD=-0.23; 95% CI: −0.37 to −0.09;P=0.001). These effects were also significant in patients undergoing chemotherapyP<0.0001. Nonsignificant differences were found for resistance training interventionsP=0.30. Slight evidence of publication bias was observedP=0.04. The studies had a low risk of bias (PEDro scale mean score of 6.4 (standard deviation (SD) ± 1.0)).Conclusion. Supervised multimodal exercise interventions including aerobic, resistance, and stretching exercises are effective in controlling CRF. These findings suggest that these exercise protocols should be included as a crucial part of the rehabilitation programs for cancer survivors and patients during anticancer treatments.
A Zero-Watermarking Scheme for Vector Map Based on Feature Vertex Distance Ratio
Authors: Peng Yuwei , Yue Mingliang
Published: June 2015

With the rapid development of GIS and computer techniques, vector map data has been widely used in many fields. Since the production of map data is very costly, illegal copying will result in huge loss for data owners. In order to protect the copyright of vector data, digital watermarking has been employed in recent years. In this paper, a zero-watermarking scheme for vector map data is proposed. In the proposed scheme, FVDR (feature vertex distance ratio) is constructed based on the feature vertices of objects. The feature data, FVDR, is combined with watermark to generate the zero-watermark. Due to the specially designed cover data, the proposed scheme is robust to geometrical attacks, vertex attacks, and object attacks. The results of extensive experiments also demonstrate the robustness of the proposed scheme.
Spatial Dependence of Physical Attributes and Mechanical Properties of Ultisol in a Sugarcane Field
Authors: Tavares Uilka Elisa , Monteiro Rolim Mário , Souza de Oliveira Veronildo , Maria Regis Pedrosa Elvira , Siqueira Glécio Machado , Guedes Magalhães Adriana
Published: June 2015

This study investigates the effect of conventional tillage and application of the monoculture of sugar cane on soil health. Variables like density, moisture, texture, consistency limits, and preconsolidation stress were taken as indicators of soil quality. The measurements were made at a 120 × 120 m field cropped with sugar cane under conventional tillage. The objective of this work was to characterize the soil and to study the spatial dependence of the physical and mechanical attributes. Then, undisturbed soil samples were collected to measure bulk density, moisture content and preconsolidation stress and disturbed soil samples for classification of soil texture, and consistency limits. The soil texture indicated that soil can be characterized as sandy clay soil and a sandy clay loam soil, and the consistency limits indicated that the soil presents an inorganic low plasticity clay. The preconsolidation tests tillage in soil moisture content around 19% should be avoided or should be chosen a management of soil with lighter vehicles in this moisture content, to avoid risk of compaction. Using geostatistical techniques mapping was possible to identify areas of greatest conservation soil and greater disturbance of the ground.
Turbulent Motion of Liquids in Hydraulic Resistances with a Linear Cylindrical Slide‐Valve
Authors: Velescu C. , Popa N. C.
Published: June 2015

We analyze the motion of viscous and incompressible liquids in the annular space of controllable hydraulic resistances with a cylindrical linear slide‐valve. This theoretical study focuses on the turbulent and steady‐state motion regimes. The hydraulic resistances mentioned above are the most frequent type of hydraulic resistances used in hydraulic actuators and automation systems. To study the liquids’ motion in the controllable hydraulic resistances with a linear cylindrical slide‐valve, the report proposes an original analytic method. This study can similarly be applied to any other type of hydraulic resistance. Another purpose of this study is to determine certain mathematical relationships useful to approach the theoretical functionality of hydraulic resistances with magnetic controllable fluids as incompressible fluids in the presence of a controllable magnetic field. In this report, we established general analytic equations to calculate (i) velocity and pressure distributions, (ii) average velocity, (iii) volume flow rate of the liquid, (iv) pressures difference, and (v) radial clearance.
Dendritic Cell-Based Immunotherapy Treatment for Glioblastoma Multiforme
Authors: Yang Liu , Guo Geng , Niu Xiao-yuan , Liu Jing
Published: June 2015

Glioblastoma multiforme (GBM) is the most malignant glioma and patients diagnosed with this disease had poor outcomes even treated with the combination of conventional treatment (surgery, chemotherapy, and radiation). Dendritic cells (DCs) are the most powerful antigen presenting cells and DC-based vaccination has the potential to target and eliminate GBM cells and enhance the responses of these cells to the existing therapies with minimal damage to the healthy tissues around them. It can enhance recognition of GBM cells by the patients’ immune system and activate vast, potent, and long-lasting immune reactions to eliminate them. Therefore, this therapy can prolong the survival of GBM patients and has wide and bright future in the treatment of GBM. Also, the efficacy of this therapy can be strengthened in several ways at some degree: the manipulation of immune regulatory components or costimulatory molecules on DCs; the appropriate choices of antigens for loading to enhance the effectiveness of the therapy; regulation of positive regulators or negative regulators in GBM microenvironment.
The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder
Authors: Gurocak Serhat , Konac Ece , Ure Iyimser , Senol Cem , Onen Ilke Hacer , Sozen Sinan , Menevse Adnan
Published: June 2015

Aim. To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS).Materials and Methods. Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method.Results. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes.Conclusions. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children.
A Mathematical Model of the Formation of Lanes in Crowds of Pedestrians Moving in Opposite Directions
Authors: Goldsztein Guillermo H.
Published: June 2015

In crowded environments, pedestrians moving in opposite directions segregate into lanes of individuals moving in the same direction. It is believed that this formation of lanes that facilitates the flow results from the individuals acting on their behalf, responding to local stimuli, without the intention of benefiting the crowd as a whole. We give evidence that this is true by developing and analyzing a simple mathematical model. Our results suggest that the simple behavior of moving out of the way to avoid imminent collisions leads to the formation of lanes of individuals moving in the same direction.
Investigation of Flow Control for the Hypersonic Inlets via Counter Flow
Authors: Fan Xiaoqiang , Tao Yuan
Published: June 2015

Experimental results show that there exist two flow fields in the hypersonic inlets when the forebody waves interact with the lip boundary, which is similar to the shock reflection ion hysteresis phenomenon. In order to improve the performance of the flow field, counterflow is applied to control the shock reflection configuration in the hypersonic inlets. For better understanding of the internal mechanism, inviscid numerical simulation is conducted. And the results demonstrate that it is feasible to realize the transition between the regular reflection configuration and the Mach reflection ion configuration in the hypersonic inlets. That is because the von Neumann criterion and detached criterion play a dominant role, respectively, in these transitions. In addition, the evolution process of Mach reflection ion in the hypersonic inlets can be divided into three stages: transmission of waves, emergence of Mach stem, and stabilization of flow field.
Interleukin-6 Stimulates Defective Angiogenesis
Authors: Gopinathan Ganga , Milagre Carla , Pearce Oliver M.T. , Reynolds Louise E. , Hodivala-Dilke Kairbaan , Leinster David A. , Zhong Haihong , Hollingsworth Robert E. , Thompson Richard , Whiteford James R. , Balkwill Frances
Published: June 2015

The cytokine IL6 has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here, we show that IL6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared with VEGF-stimulated vessels. The mechanism of IL6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies, there was an association between levels of IL6 mRNA, Jagged1, and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL6 and for understanding abnormal angiogenesis in cancers, chronic inflammatory disease, and stroke. Cancer Res; 75(15); 3098–107. ©2015 AACR.
Systematic Screening of Promoter Regions Pinpoints Functional Cis-Regulatory Mutations in a Cutaneous Melanoma Genome
Authors: Poulos Rebecca C. , Thoms Julie A.I. , Shah Anushi , Beck Dominik , Pimanda John E. , Wong Jason W.H.
Published: June 2015

With the recent discovery of recurrent mutations in the TERT promoter in melanoma, identification of other somatic causal promoter mutations is of considerable interest. Yet, the impact of sequence variation on the regulatory potential of gene promoters has not been systematically evaluated. This study assesses the impact of promoter mutations on promoter activity in the whole-genome sequenced malignant melanoma cell line COLO-829. Combining somatic mutation calls from COLO-829 with genome-wide chromatin accessibility and histone modification data revealed mutations within promoter elements. Interestingly, a high number of potential promoter mutations (n = 23) were found, a result mirrored in subsequent analysis of TCGA whole-melanoma genomes. The impact of wild-type and mutant promoter sequences were evaluated by subcloning into luciferase reporter vectors and testing their transcriptional activity in COLO-829 cells. Of the 23 promoter regions tested, four mutations significantly altered reporter activity relative to wild-type sequences. These data were then subjected to multiple computational algorithms that score the cis-regulatory altering potential of mutations. These analyses identified one mutation, located within the promoter region of NDUFB9, which encodes the mitochondrial NADH dehydrogenase (ubiquinone) 1 beta subcomplex 9, to be recurrent in 4.4% (19 of 432) of TCGA whole-melanoma exomes. The mutation is predicted to disrupt a highly conserved SP1/KLF transcription factor binding motif and its frequent co-occurrence with mutations in the coding sequence of NF1 supports a pathologic role for this mutation in melanoma. Taken together, these data show the relatively high prevalence of promoter mutations in the COLO-829 melanoma genome, and indicate that a proportion of these significantly alter the regulatory potential of gene promoters.

Implications: Genomic-based screening within gene promoter regions suggests that functional cis-regulatory mutations may be common in melanoma genomes, highlighting the need to examine their role in tumorigenesis. Mol Cancer Res; 13(8); 1218–26. ©2015 AACR.
Charting Immune Signaling Proteomes En Route to New Therapeutic Strategies
Authors: Haura Eric B. , Beg Amer A. , Rix Uwe , Antonia Scott
Published: June 2015

The activation state of an antitumor effector T cell in a tumor depends on the sum of all stimulatory signals and inhibitory signals that it receives in the tumor microenvironment. Accumulating data address the increasing complexity of these signals produced by a myriad of immune checkpoint molecules, cytokines, and metabolites. While reductionist experiments have identified key molecules and their importance in signaling, less clear is the integration of all these signals that allows T cells to guide their responses in health and in disease. Mass spectrometry–based proteomics is well poised to offer such insights, including monitoring emergence of resistance mechanisms to immunotherapeutics during treatments. A major application of this technology is in the discovery and characterization of small-molecule agents capable of enhancing the response to immunotherapeutic agents. Such an approach would reinvigorate small-molecule drug development aimed not at tumor cells but rather at tumor-resident T cells capable of producing dramatic and durable antitumor responses. Cancer Immunol Res; 3(7); 714–20. ©2015 AACR.
Contribution of Paranasal Sinuses to the Acoustic Properties of the Nasal Tract
Authors: Havel Miriam , Hofmann Gert , Mürbe Dirk , Sundberg Johan
Published: June 2015

Background: The contribution of the nasal and paranasal cavities to the vocal tract resonator properties is unclear. Here we investigate these resonance phenomena of the sinonasal tract in isolation in a cadaver and compare the results with those gained in a simplified brass tube model. Methods: The resonance characteristics were measured as the response to sine sweep excitation from an earphone. In the brass model the earphone was placed at the closed end and in the cadaver in the epipharynx. The response was picked up by a microphone placed at the open end of the model and at the nostrils, respectively. A shunting cavity with varied volumes was connected to the model and the effects on the response curve were determined. In the cadaver, different conditions with blocked and unblocked middle meatus and sphenoidal ostium were tested. Additionally, infundibulotomy was performed allowing direct access to and selective occlusion of the maxillary ostium. Results: In both the brass model and the cadaver, a baseline condition with no cavities included produced response curves with clear resonance peaks separated by valleys. Marked dips occurred when shunting cavities were attached to the model. The frequencies of these dips decreased with increasing shunting volume. In the cadaver, a marked dip was observed after removing the unilateral occlusion of the middle meatus and the sphenoidal ostium. Another marked dip was detected at low frequency after removal of the occlusion of the maxillary ostium following infundibulotomy. Conclusion: Combining measurements on a simplified nasal model with measurements in a cadaveric sinonasal tract seems a promising method for shedding light on the acoustic properties of the nasal resonator. © 2014 S. Karger AG, Basel
Was Hypervascular Hepatocellular Carcinoma Visible on Previous Gadoxetic Acid-Enhanced Magnetic Resonance Images?
Authors: Ichikawa Shintaro , Ichikawa Tomoaki , Motosugi Utaroh , Sano Katsuhiro , Morisaka Hiroyuki , Enomoto Nobuyuki , Matsuda Masanori , Fujii Hideki
Published: June 2015

Background: During the follow-up of patients with chronic liver disease, hypervascular hepatocellular carcinomas (HCCs) can develop either from pre-existing high-risk nodules or by de novo hepatocarcinogenesis. The purpose of this study was to evaluate, by retrospective analysis, the detectability and signal intensity on previous hepatocyte-phase gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) of hypervascular HCC initially detected on current EOB-MRIs. Methods: We examined 50 initially detected hypervascular HCCs that showed typical enhancement features on EOB-MRI in 39 patients whose previous EOB-MRI images obtained 6-19 months earlier were available. The detectability of each hypervascular HCC on the hepatocyte phase images of previous EOB-MRIs was assessed. The imaging features on hepatocyte-phase images of previous EOB-MRIs at the locations where hypervascular HCCs were found on the current EOB-MRI images were classified as detectable or undetectable. The signal intensities of detectable nodules (defined as group A) on hepatocyte-phase images of previous EOB-MRIs were classified as hypo-, iso-, or hyperintensity. Nodules undetectable on the hepatocyte-phase images of previous EOB-MRIs were assigned to group B. Results: Twenty-two (22/50, 44%) hypervascular HCCs were detectable on the earlier hepatocyte phase images (group A). In contrast, 28 (28/50, 56%) hypervascular HCCs were not detectable on the hepatocyte phase of earlier EOB-MRI images (group B). Conclusion: When the previous EOB-MRI images were used as the reference, more than half (28/50, 56%) of hypervascular HCCs initially appearing on the current EOB-MRI images were found not to have developed from nodules detectable on the previous MRIs through the traditionally accepted process of multistep carcinogenesis. Instead, they seemed to have developed via an “imaging-occult” process of carcinogenesis in patients with chronic liver diseases.
Vestibular Functions of Hereditary Hearing Loss Patients with GJB2 Mutations
Authors: Tsukada Keita , Fukuoka Hisakuni , Usami Shin-ichi
Published: June 2015

Objectives: Mutations in the GJB2 gene have been of particular interest as it is the most common causative gene for congenital deafness in all populations. Detailed audiological features, including genotype-phenotype correlations, have been well documented. However, in spite of abundant gene as well as protein expression in the vestibular end organs, neither vestibular symptoms nor vestibular functions have yet been elucidated. In the present study, vestibular functions were evaluated in patients diagnosed with GJB2-related deafness. Subjects and Methods: Vestibular functions were evaluated by caloric test and cervical vestibular evoked myogenic potential (cVEMP) testing in 24 patients with biallelic GJB2 mutations. Results and Discussion: Twenty-one of 23 patients (91.3%) had normal caloric responses and significantly lower cVEMP amplitudes than the control subjects. In the patients who were able to undergo vestibular testing, the mostly normal reactions to caloric testing indicated that the lateral semicircular canal was intact. However, the majority of GJB2 patients showed low cVEMP reactions, indicating a saccular defect.
The Anti-Microbial Peptide LL-37/CRAMP Is Elevated in Patients with Liver Diseases and Acts as a Protective Factor during Mouse Liver Injury
Authors: Wertenbruch Svenja , Drescher Hannah , Grossarth Vera , Kroy Daniela , Giebeler Arne , Erschfeld Stephanie , Heinrichs Daniel , Soehnlein Oliver , Trautwein Christian , Brandenburg Lars-Ove , Streetz Konrad
Published: June 2015

Background: Antimicrobial peptides (AMP) are an important defense mechanism of the innate immune system and can modulate the course of various diseases. However, their significance during liver pathogenesis is currently not well defined. Methods: Patients with liver diseases were analyzed for LL-37/CRAMP, human beta-defensin-2 (hBD2), and complement 5a (C5a) serum levels. Mice deficient in CRAMP (Cathelicidin-related Antimicrobial Peptide), the mouse homolog for human LL-37, were fed with a methionine- and choline-deficient diet (MCD) and underwent bile-duct ligation (BDL). Results: First, serum samples from patients with chronic liver diseases were investigated. Therefore, significantly enhanced levels for LL-37, hBD2, and complement C5a were detected, all of which comprise antimicrobial properties. Next, CRAMP-knockout (CRAMP-KO) mice were investigated, to better define a functional role of LL-37/CRAMP in animal models of liver diseases. MCD feeding and bile-duct ligation of CRAMP-KO mice resulted in an enhanced degree of liver injury during the early treatment phase. MCD feeding in CRAMP-KO mice led to stronger intrahepatic fat accumulation and significantly enhanced matrix remodeling, whereas BDL caused more extensive liver necrosis. At the late 28 days time point, MCD-fed CRAMP-KO mice displayed a higher intrahepatic fat load. Long-term changes in bile-duct-ligated mice included higher collagen content as a sign of enhanced fibrosis progression if CRAMP was absent. Conclusion: The study shows a clear correlation of antimicrobial peptide serum levels in patients with chronic liver diseases. Furthermore, we were able to demonstrate protective functions of LL-37/CRAMP in two independent mouse models of chronic liver injury.
Biomechanics of the Ageing Foot and Ankle: A Mini-Review
Authors: Menz Hylton B.
Published: June 2015

Foot pain is highly prevalent in older people and has a significant detrimental impact on mobility and quality of life. In recent years, there has been increased interest in exploring the biomechanical factors that may contribute to the development of foot disorders and the associated impairment of mobility in this age group. Studies have shown that with advancing age, there is a general tendency for the foot to exhibit increased soft tissue stiffness, a decreased range of motion, decreased strength and a more pronated posture as well as to function in a more pronated position with reduced joint mobility and less efficient propulsion when walking. These changes may contribute to the development of foot pain, impair performance in functional weight-bearing activities and increase the risk of falls. However, plantar pressure analysis technology has considerable potential to assist in optimising the design of interventions to redistribute load away from high-pressure areas, thereby alleviating foot symptoms and improving mobility in older people.
Clinicopathological Features and Outcomes of IgA Nephropathy with Hematuria and/or Minimal Proteinuria
Authors: Tan Min , Li Wenge , Zou Guming , Zhang Cong , Fang Jing
Published: June 2015

Background/Aims: Information regarding the clinical and histological prognostic factors of IgA nephropathy (IgAN) is mostly derived from patients in whom diagnostic renal biopsies were performed because their proteinuria levels were higher than 1-2 g/d. The clinicopathological features and outcomes of IgAN patients presenting with normal blood pressure, normal renal function, hematuria and minimal or no proteinuria are not well described. We therefore conducted a study of the clinicopathological features and outcomes in IgAN patients with these characteristics. Methods: The clinical, laboratory, and pathological manifestations and long-term outcomes of all IgAN patients with the above-mentioned characteristics were collected. The relationships between renal pathology, injury, long-term outcomes and clinical factors were studied, and the risk factors of IgAN were analyzed using multivariate logistic regression. Results: Of all of the renal biopsy cases, IgAN with the above features accounted for 8.9%. Among these patients, 67.2% (253) showed simultaneous hematuria and proteinuria, 23.1% (87) showed only hematuria, and 9.7% (36) showed only proteinuria. Additionally, 33.8% (127) patients showed macroscopic hematuria and 65.1% (245) had a prodromal infection. Regarding renal pathological changes, 45.5% (171) of the patients were unexpectedly classified as Grade II to IV (Hass classification). Proteinuria at the time of renal biopsy was an independent predictor of more severe renal pathological injury. After a median follow-up of 75 months, 61 (16.2%) patients experienced adverse events. Among these patients, 28 (7.45%) exhibited hypertension, 22 (5.85%) presented proteinuria levels >1 g/24 h, and 11 (2.9%) developed impaired renal function. Conclusions: Severe renal histological injury may be observed in some IgAN patients with benign clinical characteristics. Proteinuria is an independent predictor of severe renal pathological injury in IgAN patients with mild proteinuria. More severe pathological injury (> Grade II, Hass classification) are predictors of poor prognosis.
Azacitidine Pre-Treatment Followed by Reduced-Intensity Stem Cell Transplantation in Patients with Higher-Risk Myelodysplastic Syndrome
Authors: Ahn Jae-Sook , Kim Yeo-Kyeoung , Min Yoo Hong , Cheong June-Won , Jang Jun Ho , Jung Chul Won , Kim In Ho , Yoon Hwi-Joong , Lee Hong Ghi , Sohn Sang Kyun , Moon Joon Ho , Kim Hawk , Kim Yoo-Jin , Won Jong-Ho , Chung Joo-Seop , Mun Yeung Chul , Lee Je-Hwan , Kim Hyeoung-Joon ,   The Korean Society of Hematology AML/MDS Working Party
Published: June 2015

Azacitidine (AZA) is commonly used in patients with myelodysplastic syndrome (MDS). To determine the role of AZA before allogeneic stem cell transplantation (allo-SCT), we conducted a prospective study of AZA pre-treatment followed by allo-SCT in patients with higher-risk MDS. Twenty-one patients who were scheduled for their third to sixth cycle of AZA pre-treatment followed by allo-SCT were enrolled. AZA pre-treatment was interrupted early in 3 patients (14.3%) because of leukaemic transformation or death. The overall response rate to AZA pre-treatment was 57.1%. There were 2 cases of complete remission, 1 case of partial remission, and 9 cases of haematologic improvement. Fourteen patients (66.7%) received the planned allo-SCT and 5 patients were alive at the last follow-up. Three-year progression-free survival (PFS) and 3-year overall survival (OS) in the 14 patients who received allo-SCT were 30.0% (95% CI 3.3-56.7) and 42.9% (95% CI 17.1-68.7), respectively. PFS and OS were not influenced by response to AZA pre-treatment (p > 0.05). In this study, AZA had a role as a bridge therapy to prevent leukaemic transformation prior to selection of a donor for allo-SCT and showed low toxicity. It may be considered in patients with higher-risk MDS.
In School-Age Children Who Were Born Very Preterm Sleep Efficiency Is Associated with Cognitive Function
Authors: Hagmann-von Arx Priska , Perkinson-Gloor Nadine , Brand Serge , Albert Djana , Holsboer-Trachsler Edith , Grob Alexander , Weber Peter , Lemola Sakari
Published: June 2015

Aims: This study examined whether the association between sleep duration, as well as sleep continuity, and cognitive function differs between normally developing preterm children compared to full-term children during middle childhood. Methods: A total of 58 early preterm (<32 weeks' gestation) and 55 full-term children, aged 6-10 years and enrolled in elementary school, were assessed on sleep duration, sleep continuity and cognitive function. We used in-home polysomnographic recordings of total sleep time, sleep efficiency and nocturnal awakenings. Cognitive tests included intelligence, arithmetic, selective attention, verbal memory, and visuospatial memory. Results: Preterm children showed poorer performance in intelligence, arithmetic, selective attention, and visuospatial memory (d = 0.38-0.79, p < 0.05) and more objectively assessed nocturnal awakenings (d = 0.40, p = 0.03) than full-term children. Associations of sleep efficiency and cognitive functions (intelligence, arithmetic, selective attention, visuospatial memory) were positive and stronger for preterm children (β = 0.17-0.31, p < 0.05), while they were nonsignificant for full-term children. Conclusion: Results confirm lower cognitive test scores and more nocturnal awakenings in normally developing early preterm children compared to full-term children. Furthermore, poor sleep efficiency may aggravate cognitive deficits, particularly in children who are more vulnerable due to premature birth.
Predictors of Outcome among Pathological Gamblers Receiving Cognitive Behavioral Group Therapy
Authors: Jiménez-Murcia Susana , Granero Roser , Fernández-Aranda Fernando , Arcelus Jon , Aymamí M. Neus , Gómez-Peña Monica , Tárrega Salome , Moragas Laura , del Pino-Gutiérrez Amparo , Sauchelli Sarah , Fagundo Ana B. , Brewin Nicola , Menchón Jose M.
Published: June 2015

Aims: The aim of this study was to evaluate posttreatment changes of individuals with a diagnosis of gambling disorder (GD) treated with group cognitive behavioral therapy (CBT), to assess the potential moderator effect of sex on CBT outcome, and to explore the best predictors of posttreatment changes, relapse, and dropout rates. Methods: A cohort design was applied with a prospective follow-up. The sample comprised 440 patients and the CBT intervention consisted of 16 weekly outpatient group sessions and a 3-month follow-up period. Results: Patients showed significant improvements in both the level of psychopathology and the severity of the gambling behavior. High self-transcendence and the involvement of the spouse or partner in the therapy predicted a higher risk of relapse. Younger age and low education predicted a higher risk of dropout. Conclusion: Many patients with GD can be treated with strategies to improve self-control and emotional regulation, but other techniques should be incorporated to address the individual characteristics of each patient. This is particularly important in group therapy, in which the same treatment is applied to several patients simultaneously. The involvement of a family member needs to be carefully considered since it may have a negative effect on the response to treatment if not adequately managed.
Progressive Structural Brain Changes and NRG1 Gene Variants in First-Episode Nonaffective Psychosis
Authors: Suárez-Pinilla Paula , Roíz-Santiañez Roberto , Mata Ignacio , Ortiz-García de la Foz Victor , Brambilla Paolo , Fañanas Lourdes , Valle-San Román Natalia , Crespo-Facorro Benedicto
Published: June 2015

Background: Structural brain abnormalities are already present during the early phases of psychosis, but factors underlying brain volume changes are still not well understood. The neuregulin 1 gene (NRG1), influencing neurodevelopment and neuroplasticity, has been associated with schizophrenia. Our aim was to examine whether variations in the NRG1 gene (SNP8NRG221132, SNP8NRG6221533 and SNP8NRG243177 polymorphisms) influence longitudinal changes in the brain during a first episode of psychosis (FEP). Methods: A 3-year follow-up magnetic resonance imaging (MRI) study was performed. Fifty-nine minimally medicated patients who were experiencing FEP and 14 healthy control individuals underwent genotyping and structural brain MRI at baseline and at 1- and 3-year follow-up. A comparison of brain volumes, gray matter, white matter (WM), lateral ventricles (LV), cortical cerebrospinal fluid, and thalamus and caudate was made between the groups according to their genotype. Results: In patients, the SNP8NRG6221533 risk C allele was significantly associated with increased LV volume across time. C allele carriers had significantly less WM compared with subjects homozygous for the T allele after the follow-up. No other significant differences were observed among subgroups. No significant changes according to the genotypes were found in healthy individuals. Conclusion: Our findings suggest that variations of neurodevelopment-related genes, such as the NRG1 gene, can contribute to brain abnormalities described in early phases of schizophrenia and progressive changes during the initial years of the illness. To our knowledge, it is the first time that a relation between NRG1 polymorphisms and longitudinal brain changes is reported.
Effect of Clozapine and Other Antipsychotics on the Level of Platelet-Associated Autoantibodies in Children with Schizophrenia: A Longitudinal Follow-Up Study
Authors: Ebert Tanya , Schechtman Mila , Midbari Yael , Weizman Abraham , Shinitzky Meir , Spivak Baruch
Published: June 2015

Background: Previous studies have demonstrated significantly higher blood titers of platelet-associated autoantibodies (PAA) in adult schizophrenia patients compared to normal healthy subjects. In addition, young adult schizophrenia patients at their early stages of the disorder displayed higher PAA titers than older patients with longer duration of the disorder. Aim: To assess longitudinally the blood titers of PAA in inpatients with childhood-onset schizophrenia at admission, after short- and long-term follow-up, and the correlation of these titers with the response to clozapine and other antipsychotic treatments. Methods: Thirty children, age range of 6-12 (mean ± SD: 9.6 ± 1.5 years), with DSM-IV TR schizophrenia in active psychotic state were assessed 3 times: at baseline, after short-term (8-17 weeks; n = 26) and after long-term follow-up (33-170 weeks; n = 19). The blood titers of PAA were analyzed using ELISA and expressed by a linear optical density (OD) scale. A test recording >1.4 OD units was predefined as the positive cutoff value. Results: On long-term follow-up, 9 out of the 17 children who were PAA-positive at baseline became PAA-negative: 7 already after 2 months of clozapine treatment and 2 following 3 years of risperidone treatment. Eight children remained PAA-positive during the entire study period. There was no significant correlation between the clinical improvement (as assessed by change in the Positive and Negative Syndrome Scale score) and the alteration in PAA levels (n = 19, r = -0.4, p = 0.088). Conclusions: High rates of positive PAA in COS patients may indicate an active autoimmune process in early-onset schizophrenia. It is concluded that PAA may serve as a biomarker for the diagnosis of COS, but does not predict the response to treatment. A transition to a PAA-negative status does not indicate an improvement in psychosis.
Treatment of Childhood Atopic Dermatitis and Economic Burden of Illness in Asia Pacific Countries
Authors: Lee Bee Wah , Detzel Patrick R.
Published: June 2015

Atopic dermatitis (AD) is a common chronic inflammatory skin condition in children. In Asia, the prevalence of AD is increasing, which is largely attributed to environmental and socioeconomic factors including family income, parental education, lifestyle and metropolitan living. Current clinical guidelines recommend a stepped approach in the management of eczema in children, with treatment steps tailored to the severity of the eczema. To address the skin barrier dysfunction, skin hydration and the application of emollients is essential. There is evidence supporting the use of bleach baths as an antimicrobial therapy against Staphylococcus aureus. In patients in whom topical treatment fails, wet wrap therapy may be considered as a treatment option before considering systemic therapies. In the second part of this article, the economic burden of AD is addressed. AD not only negatively impacts the child's quality of life but also that of the whole family and is associated with a burden on health-care costs and society. AD in an infant will lead to frequent additional visits to the pediatrician, to additional and partially expensive treatment costs and, in rare cases, to hospitalization. It is thus of utmost importance to define efficient strategies to not only treat AD but also to decrease the risk of developing the disease.
Effects of Reinnervation of the Biarticular Shoulder-Elbow Muscles on Joint Kinematics and Electromyographic Patterns of the Feline Forelimb during Downslope Walking
Authors: Livingston Beven P. , Nichols T. Richard
Published: June 2015

Full recovery of the forelimb kinematics during level and upslope walking following reinnervation of the biarticular elbow extensor suggests that the proprioceptive loss is compensated by other sensory sources or altered central drive, yet these findings have not been explored in downslope walking. Kinematics and muscle activity of the shoulder and elbow during downslope locomotion following reinnervation of the feline long head of the triceps brachii (TLo) and biceps brachii (Bi) were evaluated (1) during paralysis and (2) after the motor function was recovered but the proprioceptive feedback was permanently disrupted. The step cycle was examined in three walking conditions: level (0%), -25% grade (-14° downslope) and -50% grade (-26.6° downslope). Measurements were taken prior to and at three time points (2 weeks, and 1 and 12+ months) after transecting and suturing the radial and musculocutaneous nerves. There was an increase in the yield (increased flexion) at the elbow and less extensor activity duration of flexion during stance as the downslope grade increased. There were two notable periods of eccentric contractions (active lengthening) providing an apparent ‘braking' action. Paralysis of the TLo and the Bi resulted in uncompensated alterations in shoulder-elbow kinematics and motor activity during the stance phase. However, unlike the case for the level and upslope conditions, during both paralysis and reinnervation, changes in interjoint coordination persisted for the downslope condition. The lack of complete recovery in the long term suggests that the autogenic reflexes contribute importantly to muscle and joint stiffness during active lengthening.
Bile Acids as Hormones: The FXR-FGF15/19 Pathway
Authors: Kliewer Steven A. , Mangelsdorf David J.
Published: June 2015

While it has long been recognized that bile acids are essential for solubilizing lipophilic nutrients in the small intestine, the discovery in 1999 that bile acids serve as ligands for the nuclear receptor farnesoid X receptor (FXR) opened the floodgates in terms of characterizing their actions as selective signaling molecules. Bile acids act on FXR in ileal enterocytes to induce the expression of fibroblast growth factor (FGF)15/19, an atypical FGF that functions as a hormone. FGF15/19 subsequently acts on a cell surface receptor complex in hepatocytes to repress bile acid synthesis and gluconeogenesis, and to stimulate glycogen and protein synthesis. FGF15/19 also stimulates gallbladder filling. Thus, the bile acid-FXR-FGF15/19 signaling pathway regulates diverse aspects of the postprandial enterohepatic response. Pharmacologically, this endocrine pathway provides exciting new opportunities for treating metabolic disease and bile acid-related disorders such as primary biliary cirrhosis and bile acid diarrhea. Both FXR agonists and FGF19 analogs are currently in clinical trials.