bluuebunny/crossref_metadata_2025 huggingface dataset:
Origin and Fate of Organic Compounds in Water: Characterization by Compound-Specific Stable Isotope Analysis
Authors: Schmidt Torsten C. , Jochmann Maik A.
Published: June 2012

Within the past 15 years, compound-specific stable isotope analysis has continued to increase in popularity in the area of contaminant hydrology of organic molecules. In particular, in cases where concentration data alone are insufficient to elucidate environmental processes unequivocally, the isotope signature can provide additional unique information. Specifically, it can help answer questions about contaminant source apportionment, quantification of biotic and abiotic processes, and identification of transformation reactions on a mechanistic level. We review advances in laboratory and field investigations and exemplary applications in contaminant hydrology via stable isotope analysis. We also highlight future directions in the field.
Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine
Authors: de Wit Nicole , Derrien Muriel , Bosch-Vermeulen Hanneke , Oosterink Els , Keshtkar Shohreh , Duval Caroline , de Vogel-van den Bosch Johan , Kleerebezem Michiel , Müller Michael , van der Meer Roelof
Published: June 2012

We studied the effect of dietary fat type, varying in polyunsaturated-to-saturated fatty acid ratios (P/S), on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1), or safflower oil (HF-SO; P/S 7.8) for 8 wk. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared with the HF-OO, HF-SO, or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes-to-Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.
Novel Flexible Artificial Magnetic Conductor
Authors: de Cos M. E. , Las-Heras F.
Published: June 2012

A novel flexible uniplanar AMC design is presented. An AMC prototype is manufactured using laser micromachining and it is characterized under flat and bent conditions by measuring its reflection coefficient phase in an anechoic chamber. The designed prototype shows broad AMC operation bandwidth (6.96% and higher) and polarization angle independency. Its angular stability margin, when operating under oblique incidence, is also tested obtaining±8°as limit for a 14.4 cm × 14.4 cm prototype.
Managing Mental Health Disorders Resulting from Trauma through Yoga: A Review
Authors: Telles Shirley , Singh Nilkamal , Balkrishna Acharya
Published: June 2012

There are many and varied types of trauma. The extent to which trauma influences the mental health of an individual depends on the nature of trauma, as well as on the individual's coping capabilities. Often trauma is followed by depression, anxiety, and PTSD. As the pharmacological remedies for these conditions often have undesirable side-effects, nonpharmacological remedies are thought of as a possible add-on treatment. Yoga is one such mind-body intervention. This paper covers eleven studies indexed in PubMed, in which mental health disorders resulting from trauma were managed through yoga including meditation. The aim was to evaluate the use of yoga in managing trauma-related depression, anxiety, PTSD and physiological stress following exposure to natural calamities, war, interpersonal violence, and incarceration in a correctional facility. An attempt has also been made to explore possible mechanisms underlying benefits seen. As most of these studies were not done on persons exposed to trauma that had practiced yoga, this is a definite area for further research.
Combined Transfection of the Three Transcriptional Factors, PDX-1, NeuroD1, and MafA, Causes Differentiation of Bone Marrow Mesenchymal Stem Cells into Insulin-Producing Cells
Authors: Qing-Song Guo , Ming-Yan Zhu , Lei Wang , Xiang-Jun Fan , Yu-Hua Lu , Zhi-Wei Wang , Sha-Jun Zhu , Yao Wang , Yan Huang
Published: June 2012

Aims. The goal of cell transcription for treatment of diabetes is to generate surrogateβ-cells from an appropriate cell line. However, the induced replacement cells have showed less physiological function in producing insulin compared with normalβ-cells.Methods. Here, we report a procedure for induction of insulin-producing cells (IPCs) from bone marrow murine mesenchymal stem cells (BM-mMSCs). These BM-mMSCs have the potential to differentiate into insulin-producing cells when a combination of PDX-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation-1), and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) genes are transfected into them and expressed in these cells.Results. Insulin biosynthesis and secretion were induced in mMSCs into which these three genes have been transfected and expressed. The amount of induced insulin in the mMSCs which have been transfected with the three genes together is significantly higher than in those mMSCs that were only transfected with one or two of these three genes. Transplantation of the transfected cells into mice with streptozotocin-induced diabetes results in insulin expression and the reversal of the glucose challenge.Conclusions. These findings suggest major implications for cell replacement strategies in generation of surrogateβ-cells for the treatment of diabetes.
A Compact UWB Indoor and Through-Wall Radar with Precise Ranging and Tracking
Authors: Yu Yinan , Yang Jian , McKelvey Tomas , Stoew Borys
Published: June 2012

Ultrawideband (UWB) technology has many advantages compared to its narrowband counterpart in many applications. We present a new compact low-cost UWB radar for indoor and through-wall scenario. The focus of the paper is on the development of the signal processing algorithms for ranging and tracking, taking into account the particular properties of the UWB CMOS transceiver and the radiation characteristics of the antennas. Theoretical analysis for the algorithms and their evaluations by measurements are presented in the paper. The ranging resolution of this UWB radar has achieved 1-2 mm RMS accuracy for a moving target in indoor environment over a short range, and Kalman tracking algorithm functions well for the through-wall detection.
MesoporousTiO2Micro-Nanometer Composite Structure: Synthesis, Optoelectric Properties, and Photocatalytic Selectivity
Authors: Liu Kun , Zhu Lianjie , Jiang Tengfei , Sun Youguang , Li Hongbin , Wang Dejun
Published: June 2012

Mesoporous anatase TiO2micro-nanometer composite structure was synthesized by solvothermal method at 180°C, followed by calcination at 400°C for 2 h. The as-prepared TiO2was characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Fourier transform infrared spectrum (FT-IR). The specific surface area and pore size distribution were obtained from N2adsorption-desorption isotherm, and the optoelectric property of the mesoporous TiO2was studied by UV-Vis absorption spectrum and surface photovoltage spectra (SPS). The photocatalytic activity was evaluated by photodegradation of sole rhodamine B (RhB) and sole phenol aqueous solutions under simulated sunlight irradiation and compared with that of Degussa P-25 (P25) under the same conditions. The photodegradation preference of this mesoporous TiO2was also investigated for an RhB-phenol mixed solution. The results show that the TiO2composite structure consists of microspheres (∼0.5–2 μm in diameter) and irregular aggregates (several hundred nanometers) with rough surfaces and the average primary particle size is 10.2 nm. The photodegradation activities of this mesoporous TiO2on both RhB and phenol solutions are higher than those of P25. Moreover, this as-prepared TiO2exhibits photodegradation preference on RhB in the RhB-phenol mixture solution.
Manganese Superoxide Dismutase Regulates a Metabolic Switch during the Mammalian Cell Cycle
Authors: Sarsour Ehab H. , Kalen Amanda L. , Xiao Zhen , Veenstra Timothy D. , Chaudhuri Leena , Venkataraman Sujatha , Reigan Philip , Buettner Garry R. , Goswami Prabhat C.
Published: June 2012

Proliferating cells consume more glucose to cope with the bioenergetics and biosynthetic demands of rapidly dividing cells as well as to counter a shift in cellular redox environment. This study investigates the hypothesis that manganese superoxide dismutase (MnSOD) regulates cellular redox flux and glucose consumption during the cell cycle. A direct correlation was observed between glucose consumption and percentage of S-phase cells in MnSOD wild-type fibroblasts, which was absent in MnSOD homozygous knockout fibroblasts. Results from electron paramagnetic resonance spectroscopy and flow cytometric assays showed a significant increase in cellular superoxide levels in S-phase cells, which was associated with an increase in glucose and oxygen consumption, and a decrease in MnSOD activity. Mass spectrometry results showed a complex pattern of MnSOD-methylation at both lysine (68, 89, 122, and 202) and arginine (197 and 216) residues. MnSOD protein carrying a K89A mutation had significantly lower activity compared with wild-type MnSOD. Computational-based simulations indicate that lysine and arginine methylation of MnSOD during quiescence would allow greater accessibility to the enzyme active site as well as increase the positive electrostatic potential around and within the active site. Methylation-dependent changes in the MnSOD conformation and subsequent changes in the electrostatic potential around the active site during quiescence versus proliferation could increase the accessibility of superoxide, a negatively charged substrate. These results support the hypothesis that MnSOD regulates a “metabolic switch” during progression from quiescent through the proliferative cycle. We propose MnSOD as a new molecular player contributing to the Warburg effect. Cancer Res; 72(15); 3807–16. ©2012 AACR.
PTEN and NF1 Inactivation in Schwann Cells Produces a Severe Phenotype in the Peripheral Nervous System That Promotes the Development and Malignant Progression of Peripheral Nerve Sheath Tumors
Authors: Keng Vincent W. , Rahrmann Eric P. , Watson Adrienne L. , Tschida Barbara R. , Moertel Christopher L. , Jessen Walter J. , Rizvi Tilat A. , Collins Margaret H. , Ratner Nancy , Largaespada David A.
Published: June 2012

The genetic evolution from a benign neurofibroma to a malignant sarcoma in patients with neurofibromatosis type 1 (NF1) syndrome remains unclear. Schwann cells and/or their precursor cells are believed to be the primary pathogenic cell in neurofibromas because they harbor biallelic neurofibromin 1 (NF1) gene mutations. However, the phosphatase and tensin homolog (Pten) and neurofibromatosis 1 (Nf1) genes recently were found to be comutated in high-grade peripheral nerve sheath tumors (PNST) in mice. In this study, we created transgenic mice that lack both Pten and Nf1 in Schwann cells and Schwann cell precursor cells to validate the role of these two genes in PNST formation in vivo. Haploinsufficiency or complete loss of Pten dramatically accelerated neurofibroma development and led to the development of higher grade PNSTs in the context of Nf1 loss. Pten dosage, together with Nf1 loss, was sufficient for the progression from low-grade to high-grade PNSTs. Genetic analysis of human malignant PNSTs (MPNST) also revealed downregulation of PTEN expression, suggesting that Pten-regulated pathways are major tumor-suppressive barriers to neurofibroma progression. Together, our findings establish a novel mouse model that can rapidly recapitulate the onset of human neurofibroma tumorigenesis and the progression to MPNSTs. Cancer Res; 72(13); 3405–13. ©2012 AACR.
Extensive Promoter DNA Hypermethylation and Hypomethylation Is Associated with Aberrant MicroRNA Expression in Chronic Lymphocytic Leukemia
Authors: Baer Constance , Claus Rainer , Frenzel Lukas P. , Zucknick Manuela , Park Yoon Jung , Gu Lei , Weichenhan Dieter , Fischer Martina , Pallasch Christian Philipp , Herpel Esther , Rehli Michael , Byrd John C. , Wendtner Clemens-Martin , Plass Christoph
Published: June 2012

Dysregulated microRNA (miRNA) expression contributes to the pathogenesis of hematopoietic malignancies, including chronic lymphocytic leukemia (CLL). However, an understanding of the mechanisms that cause aberrant miRNA transcriptional control is lacking. In this study, we comprehensively investigated the role and extent of miRNA epigenetic regulation in CLL. Genome-wide profiling conducted on 24 CLL and 10 healthy B cell samples revealed global DNA methylation patterns upstream of miRNA sequences that distinguished malignant from healthy cells and identified putative miRNA promoters. Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation. DNA hypomethylation accounted for more than 60% of all aberrant promoter-associated DNA methylation in CLL, and promoter DNA hypomethylation was restricted to well-defined regions. Individual hyper- and hypomethylated promoters allowed discrimination of CLL samples from healthy controls. Promoter DNA methylation patterns were confirmed in an independent patient cohort, with 11 miRNAs consistently showing an inverse correlation between DNA methylation status and expression level. Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL. Cancer Res; 72(15); 3775–85. ©2012 AACR.
Molecular Pathways: Targeting Phosphoinositide 3-Kinase p110-Delta in Chronic Lymphocytic Leukemia
Authors: Herman Sarah E.M. , Johnson Amy J.
Published: June 2012

The advent of targeted therapy, specifically to the B-cell receptor (BCR), has changed the convention for the treatment of chronic lymphocytic leukemia (CLL). The phosphoinositide 3-kinase (PI3K) pathway, activated upstream by the BCR, receptor tyrosine kinases, and cytokine receptors, has been a potential target for a multitude of cancers, but until the recent introduction of isoform-specific inhibitors has not been widely used. In this review, we focus on describing the intricate upstream and downstream signaling, leading to cell survival mediated by PI3K in B cells with a specific focus on the impact and importance of the p110δ isoform (which is localized to hematopoietic cells and regulates distinct cellular functions in B cells). In addition, the clinical advances from targeting p110δ are described, with a focus on clinical outcome, toxicities, and rational combination therapies. The experiences with p110δ in CLL have led to a more fundamental understanding of CLL signaling defects and may be predictive of other BCR-directed therapeutics. Clin Cancer Res; 18(15); 4013–8. ©2012 AACR.
Downregulation of the Ubiquitin-Proteasome System in Normal Colonic Macrophages and Reinduction in Inflammatory Bowel Disease
Authors: Hetzenecker A.M. , Seidl M.C. , Kosovac K. , Herfarth H. , Kellermeier S. , Obermeier F. , Falk W. , Schoelmerich J. , Hausmann M. , Rogler G.
Published: June 2012

Background: In normal mucosa, intestinal lamina propria macrophages (IMACs) maintain tolerance against food antigens and the commensal bacterial flora. Several mechanisms have been identified that mediate tolerance. The ubiquitin-proteasome system (UPS) is a large multiprotein complex that degrades cellular proteins. As the UPS may modulate immune functions of IMACs, we performed a detailed investigation of UPS expression and function under normal conditions and in cells derived from patients suffering from inflammatory bowel disease (IBD). Methods: IMACs were isolated from intestinal mucosa. mRNA expression of macrophages differentiated in vitro (i.v. MACs) and IMACs was compared by Affymetrix® oligonucleotide arrays. Quantitative Taqman-PCR was performed on five exemplary proteasomal and five ubiquitinylation genes each. Proteins were analyzed by immunohistochemistry and Western blotting. Proteasome function was assessed by a fluorimetric test. Results: Affymetrix analysis showed downregulation of mRNA expression of almost all represented proteasomal and of 22 ubiquitination-associated genes in IMACs as compared to i.v. MACs and monocytes. By quantitative PCR, up to tenfold higher mRNA expression of 10 exemplary genes of the UPS (UBE2A, UBE2D2, UBE2L6, USP14, UBB and ATPase2, β2, β5, β2i/MECL-1, β5i/LMP7) was demonstrated in i.v. MACs as compared to IMACs. Immunohistochemistry and Western blots confirmed these findings in intestinal mucosa of controls and patients suffering from diverticulitis. In contrast, a significant increase in protein amounts was found in mucosa of patients with IBD. Conclusion: Reduced expression of subunits of the UPS in IMACs of normal mucosa supports the concept of the presence of a nonreactive, anergic macrophage phenotype in the gut under normal conditions. Reinduction in IMACs of IBD mucosa reflects activated IMACs which can present antigenic peptides and thus support inflammation.
Reduction of Retinopathy of Prematurity in Extremely Low Gestational Age Newborns Treated with Recombinant Human Cu/Zn Superoxide Dismutase
Authors: Parad Richard B. , Allred Elizabeth N. , Rosenfeld Warren N. , Davis Jonathan M. ,   and the North American rhSOD Study Group
Published: June 2012

Background: Reactive oxygen species have been implicated in the pathogenesis of retinopathy of prematurity (ROP). Extremely low gestational age (GA) newborns (ELGANs) have the highest risk of ROP and might benefit most from treatment with antioxidants. Objectives: To determine whether recombinant human Cu/Zn superoxide dismutase (rhSOD) decreases the incidence or severity of ROP in ELGANs. Methods: A previous multicenter trial of intratracheal rhSOD for prevention of bronchopulmonary dysplasia randomized 302 preterm infants to receive intratracheal rhSOD or placebo at birth and every 48 h for 1 month. An analysis of the incidence and severity of ROP was performed in ELGANs. Results: The risk of ROP increased with decreasing GA. Within the entire cohort, no significant differences in ROP were found in the placebo versus rhSOD groups. Subgroup analysis on infants born at <26 weeks (n = 72) revealed a 22% reduction in ROP from 85% (placebo) to 66% (rhSOD) (p = 0.06). In subjects born at <25 weeks (n = 24), ROP was reduced by 53% from 85% (placebo) to 40% (rhSOD) (p = 0.03). ROP severity above stage 2 was found in 42% of placebo-treated infants but only 25% of rhSOD-treated subjects with ROP. Conclusions: This post hoc analysis suggests that rhSOD reduces the risk of developing ROP in ELGANs, although further studies are required to confirm this observation.
Feasibility and Reproducibility of a Standard Protocol for 2D Speckle Tracking and Tissue Doppler-Based Strain and Strain Rate Analysis of the Fetal Heart
Authors: Crispi Fàtima , Sepulveda-Swatson Eduardo , Cruz-Lemini Monica , Rojas-Benavente Juan , Garcia-Posada Raul , Dominguez Jesus Maria , Sitges Marta , Bijnens Bart , Gratacós Eduard
Published: June 2012

Purpose: Assessment of cardiac function in the fetal heart is challenging because of its small size and high heart rate, restricted physical access to the fetus, and impossibility of fetal ECG recording. We aimed to standardize the acquisition and postprocessing of fetal echocardiography for deformation analysis and to assess its feasibility, reproducibility, and correlation for longitudinal strain and strain rate measurements by tissue Doppler imaging (TDI) and 2D speckle tracking (2D-strain) during pregnancy. Methods: Echocardiography was performed in 56 fetuses. 2D and color TDI in apical or basal four-chamber views were recorded for subsequent analysis. Caution was taken to achieve a frame rate >70 Hz for speckle tracking and >150 Hz for TDI analysis. For each acquisition, 7.5 s of noncompressed data were stored in cine loop format and analyzed offline. Since fetal ECG information is by definition not available, aortic valve closure was marked from aortic flow and the onset of each cardiac cycle was manually indicated in the 2D images. Sample volume length was standardized at the minimum size. Two observers measured the left and right ventricular peak systolic longitudinal strain and strain-rate. Results: Strain and strain rate measurements were feasible in 93% of the TDI and 2D-strain acquisitions. The mean time spent on analyzing TDI images was 18 min, with an intraclass agreement coefficient of 0.86 (95% CI 0.77–0.92), 0.83 (95% CI 0.72–0.90), 0.96 (95% CI 0.93–0.98), and 0.86 (95% CI 0.76–0.92) for basal left and right free wall peak systolic strain and strain rate, respectively. Agreement between observers using tissue Doppler also showed high reliability. The mean time spent for 2D-strain analysis was 15 min, with an intraclass agreement coefficient of 0.97 (95% CI 0.95–0.98), 0.94 (95% CI 0.89–0.96), 0.96 (95% CI 0.93–0.98), and 0.84 (95% CI 0.73–0.90) for basal left and right free wall peak systolic strain and strain rate, respectively. Agreement between observers also showed a high reliability that was similar for TDI and 2D-strain. There was a weak correlation between TDI and 2D-strain measurements. Conclusions: A standard protocol with fixed acquisition and processing settings, including manual indication of the timing events of the cardiac cycle to correct for the lack of ECG, was feasible and reproducible for the evaluation of longitudinal ventricular strain and strain rate of the fetal heart by TDI as well as 2D-strain analysis. However, both techniques are not interchangeable as the correlation between them is relatively poor.
Effectiveness of Magnesium Citrate as Preparation for Capsule Endoscopy: A Randomized, Prospective, Open-Label, Inter-Group Trial
Authors: Ninomiya Kazeo , Yao Kenshi , Matsui Toshiyuki , Sato Yuho , Kishi Masahiro , Karashima Yoshihiko , Ishihara Hiroshi , Hirai Fumihito
Published: June 2012

Background and Aim: Capsule endoscopy (CE) is effective in the detection of small bowel lesions. Many studies have been conducted on the effectiveness of preparations in improving diagnostic yield, but an effective method has yet to be confirmed. We used magnesium citrate as preparation for CE and evaluated its effectiveness. Methods: 50 patients who underwent CE were randomly allocated to two groups – group A (preparation provided) and group B (no preparation). Group A were administered 34 g of magnesium citrate at 8 p.m. the night before the examination. Group B were not administered a laxative. Results: The cleansing efficacy score was 24.4 ± 4.4 points for group A and 22.9 ± 4.4 points for group B, with no significant difference between groups. No significant difference was seen in the large bowel arrival rate between groups: 14 cases (63.6%) for group A and 16 cases (72.7%) for group B. Conclusion: In this study, superiority was not seen for cleansing efficacy, large bowel arrival rate for the preparation method involving administration of hypertonic MC solution 12 h prior to the procedure.
Efficient Adaptively Weighted Analysis of Secondary Phenotypes in Case-Control Genome-Wide Association Studies
Authors: Li Huilin , Gail Mitchell H.
Published: June 2012

We propose and compare methods of analysis for detecting associations between genotypes of a single nucleotide polymorphism (SNP) and a dichotomous secondary phenotype (X), when the data arise from a case-control study of a primary dichotomous phenotype (D), which is not rare. We considered both a dichotomous genotype (G) as in recessive or dominant models and an additive genetic model based on the number of minor alleles present. To estimate the log odds ratio β1 relating X to G in the general population, one needs to understand the conditional distribution [D ∣ X, G] in the general population. For the most general model, [D ∣ X, G], one needs external data on P(D = 1) to estimate β1. We show that for this ‘full model’, the maximum likelihood (FM) corresponds to a previously proposed weighted logistic regression (WL) approach if G is dichotomous. For the additive model, WL yields results numerically close, but not identical, to those of the maximum likelihood FM. Efficiency can be gained by assuming that [D ∣ X, G] is a logistic model with no interaction between X and G (the ‘reduced model’). However, the resulting maximum likelihood (RM) can be misleading in the presence of interactions. We therefore propose an adaptively weighted approach (AW) that captures the efficiency of RM but is robust to the occasional SNP that might interact with the secondary phenotype to affect the risk of the primary disease. We study the robustness of FM, WL, RM and AW to misspecification of P(D = 1). In principle, one should be able to estimate β1 without external information on P(D = 1) under the reduced model. However, our simulations show that the resulting inference is unreliable. Therefore, in practice one needs to introduce external information on P(D = 1), even in the absence of interactions between X and G.
Hybrid Minimally Invasive Urethroplasty for Pan-Anterior Urethral Strictures: Initial Results
Authors: Seth Amlesh , Saini Ashish Kumar , Dogra P.N.
Published: June 2012

Introduction: To describe our minimally invasive hybrid technique for treating pan-anterior urethral stricture. Patients and Methods: From February 2009 through November 2011, 12 patients with pan-anterior urethral stricture were operated on in our unit. The bulbospongiosus muscle was mobilized on one side, and a 2.5-cm dorsolateral bulbar urethrotomy was made. A full-thickness cold knife optical internal urethrotomy was made to reach the corpus cavernosum as graft bed. A 14- to 16-cm-long, 15- to 16-mm-wide buccal/lingual mucosa graft was harvested and sutured dorsally at the site of urethrotomy, and then distally at the meatus along with meatoplasty. Results: The mean operating time was 91.66 min. The average hospital stay was 2.4 days. The Foley catheter was removed after 3 weeks. The mean Qmax preoperatively and postoperatively was 5.5 ± 1.87 and 18.83 ± 2.04 ml/s, respectively. Our mean follow-up was 18.5 ± 6.92 (6–32) months. Conclusions: Our hybrid technique provides good short-term results while promoting minimal urethral mobilization and graft vascularity.
Malignant Pleural Mesothelioma: From the Bench to the Bedside
Authors: Astoul P. , Roca E. , Galateau-Salle F. , Scherpereel A.
Published: June 2012

Optimal management of malignant pleural mesothelioma (MPM), which is mainly based on patient characteristics and clinical stage, is not clearly defined yet, although detailed, practical guidelines for these patients have been proposed by some scientific societies. Translational research, in the field of this disease, is currently in progress and different molecular oncogenic pathways leading to the growth and progression of MPM have been characterized with recent pharmaceutical developments. However, further in-depth analysis still needs to be done for a more advanced deciphering of the step-by-step process leading from early increased mesothelial cell proliferation to invasive mesothelioma, from which we are expecting the development of definitively effective therapy. Thus, this review is an overview of the recent advances in the biology of MPM and their potential therapeutic applications in the field of MPM diagnosis and treatment.
PTPN22 Polymorphism Presumably Plays a Role in the Genetic Background of Chronic Spontaneous Autoreactive Urticaria
Authors: Brzoza Z. , Grzeszczak W. , Rogala B. , Trautsolt W. , Moczulski D.
Published: June 2012

Background: The association of chronic urticaria (CU) with autoimmune disorders is relatively well proved. Protein tyrosine phosphatase-22 (PTPN22) is considered to be one of the strongest genetic factors for human autoimmunity. We decided to evaluate whether additional, non 1858C>T, PTPN22 variants are independent contributors to the risk of CU occurrence in the Polish population. Methods: A total of 91 CU patients with a positive result of autologous serum skin test and 100 healthy volunteers were enrolled in the study. The Urticaria Activity Score was used in disease intensity assessment. In all subjects rs3811021, rs1310182 and rs2488457 polymorphisms were genotyped. Results: We found a higher prevalence of –1123 C allele among CU patients. No differences in the allele and genotype distribution were found in the other analyzed polymorphisms. Haplotype construction of the three SNPs revealed statistically significant CU association of rs2488457C, rs1310182T and rs3811021T. Conclusions: Contrary to previous findings, the contribution of PTPN22 to disease susceptibility is suggested. We can speculate that CU is a genetically complex disease and that its occurrence needs multiple genetic and environmental risk factors.
Binding of Oxidized Low-Density Lipoprotein on Circulating Platelets Is increased in Patients With Acute Coronary Syndromes and Induces Platelet Adhesion to Vascular Wall In Vivo—Brief Report
Authors: Stellos Konstantinos , Sauter Reinhard , Fahrleitner Manuela , Grimm Juliane , Stakos Dimitrios , Emschermann Frederic , Panagiota Victoria , Gnerlich Stephan , Perk Annegret , Schönberger Tanja , Bigalke Boris , Langer Harald F. , Gawaz Meinrad
Published: June 2012

Objective—

Hyperlipidemia is associated with platelet hyperactivity. In the present study, we evaluated the binding of oxidized low-density lipoprotein (oxLDL) on the surface of circulating platelets in patients with stable coronary artery disease and acute coronary syndromes and its possible association with platelet activation. Furthermore, the role of oxLDL binding on platelet adhesion to collagen and endothelial cells in vitro as well as after carotid ligation in mice was investigated.

Methods and Results—

Using flow cytometry, patients with acute coronary syndromes (n=174) showed significantly enhanced oxLDL binding compared with patients with stable coronary artery disease (n=182;
P
=0.007). Platelet-bound oxLDL positively correlated with the degree of platelet activation (expression of P-selectin and activated fibrinogen receptor;
P
<0.001 for both). Plasma oxLDL was increased in patients with acute coronary syndromes compared with stable angina pectoris patients. Preincubation of isolated platelets with oxLDL, but not with native LDL, resulted in enhanced platelet adhesion to collagen and activated endothelial cells under high shear stress in vitro, as well as after carotid ligation in C57BL/6J mice and apolipoprotein E
−/−
mice fed a high cholesterol diet.

Conclusion—

Increased platelet-bound oxLDL in patients with acute coronary syndromes may play an important role in atherothrombosis, thus providing a potential future therapeutic target.
A Genome-Wide Association Study Identifies
KNG1
as a Genetic Determinant of Plasma Factor XI Level and Activated Partial Thromboplastin Time
Authors: Sabater-Lleal Maria , Martinez-Perez Angel , Buil Alfonso , Folkersen Lasse , Souto Juan Carlos , Bruzelius Maria , Borrell Montserrat , Odeberg Jacob , Silveira Angela , Eriksson Per , Almasy Laura , Hamsten Anders , Soria José Manuel
Published: June 2012

Objective—

Elevated plasma levels of coagulation factor XI (FXI) are implicated in the pathogenesis of venous thromboembolism and ischemic stroke, and polymorphisms in the
F11
gene are associated both with risk of venous thromboembolism and an elevated plasma FXI level.

Methods and Results—

Here, we report the first hypothesis-free genome-wide genetic analysis of plasma FXI levels. Two genome-wide significant loci were detected in the family-based Genetic Analysis of Idiopathic Thrombophilia 1 cohort: one located in the
kininogen 1
gene (
KNG1
) (rs710446;
P
=7.98×10
−10
) and one located in the structural
F11
gene (rs4241824;
P
=1.16×10
−8
). Both associations were replicated in a second population-based Swedish cohort. A significant effect on
KNG1
mRNA expression was also seen for the 2 most robustly FXI-associated single nucleotide polymorphisms located in
KNG1
. Furthermore, both
KNG1
single nucleotide polymorphisms were associated with activated partial thromboplastin time, suggesting that FXI may be the main mechanistic pathway by which
KNG1
and
F11
influence activated partial thromboplastin time and risk of thrombosis.

Conclusion—

These findings contribute to the emerging molecular basis of venous thromboembolism and, more importantly, help in understanding the biological regulation of a phenotype that has proved to have promising therapeutic properties in relation to thrombosis.
Association Between Sodium Intake and Change in Uric Acid, Urine Albumin Excretion, and the Risk of Developing Hypertension
Authors: Forman John P. , Scheven Lieneke , de Jong Paul E. , Bakker Stephan J.L. , Curhan Gary C. , Gansevoort Ron T.
Published: June 2012

Background—

A high-sodium diet has little short-term effect on blood pressure in nonhypertensive individuals but, for unclear reasons, is associated with hypertension if consumed long term. We hypothesized that a chronically high sodium intake would be associated with increases in biomarkers of endothelial dysfunction, specifically serum uric acid (SUA) and urine albumin excretion (UAE), and that high sodium intake would be associated with incident hypertension among those with higher SUA and UAE.

Methods and Results—

We prospectively analyzed the associations between sodium intake and the change in SUA (n=4062) and UAE (n=4146) among participants of the Prevention of Renal and Vascular End Stage Disease (PREVEND) study who were not taking antihypertensive medications. We also examined the association of sodium intake with the incidence of hypertension (n=5556) among nonhypertensive participants. After adjustment for confounders, each 1-g-higher sodium intake was associated with a 1.2-μmol/L increase in SUA (
P
=0.01) and a 4.6-mg/d increase in UAE (
P
<0.001). The relation between sodium intake and incident hypertension varied according to SUA and UAE. For each 1-g-higher sodium intake, the adjusted hazard ratio for developing hypertension was 0.98 (95% confidence interval, 0.89–1.08) among those in the lowest tertile of SUA and 1.09 (1.02–1.16) among those in the highest tertile. Corresponding hazard ratios were 0.99 (confidence interval, 0.93–1.06) among participants whose UAE was <10 mg/d and 1.18 (confidence interval, 1.07–1.29) among those whose UAE was >15 mg/d.

Conclusions—

Over time, higher sodium intake is associated with increases in SUA and UAE. Among individuals with higher SUA and urine UAE, a higher sodium intake is an independent risk factor for developing hypertension.
Histone Deacetylation Inhibition in Pulmonary Hypertension
Authors: Zhao Lan , Chen Chien-Nien , Hajji Nabil , Oliver Eduardo , Cotroneo Emanuele , Wharton John , Wang Daren , Li Min , McKinsey Timothy A. , Stenmark Kurt R. , Wilkins Martin R.
Published: June 2012

Background—

Epigenetic programming, dynamically regulated by histone acetylation, is a key mechanism regulating cell proliferation and survival. Little is known about the contribution of histone deacetylase (HDAC) activity to the development of pulmonary arterial hypertension, a condition characterized by profound structural remodeling of pulmonary arteries and arterioles.

Methods and Results—

HDAC1 and HDAC5 protein levels were elevated in lungs from human idiopathic pulmonary arterial hypertension and in lungs and right ventricles from rats exposed to hypoxia. Immunohistochemistry localized increased expression to remodeled vessels in the lung. Both valproic acid, a class I HDAC inhibitor, and suberoylanilide hydroxamic acid (vorinostat), an inhibitor of class I, II, and IV HDACs, mitigated the development of and reduced established hypoxia-induced pulmonary hypertension in the rat. Both valproic acid and suberoylanilide hydroxamic acid inhibited the imprinted highly proliferative phenotype of fibroblasts and R-cells from pulmonary hypertensive bovine vessels and platelet-derived growth factor–stimulated growth of human vascular smooth muscle cells in culture. Exposure to valproic acid and suberoylanilide hydroxamic acid was associated with increased levels of p21 and FOXO3 and reduced expression of survivin. The significantly higher levels of expression of cKIT, monocyte chemoattractant protein-1, interleukin-6, stromal-derived factor-1, platelet-derived growth factor-b, and S100A4 in R-cells were downregulated by valproic acid and suberoylanilide hydroxamic acid treatment.

Conclusions—

Increased HDAC activity contributes to the vascular pathology of pulmonary hypertension. The effectiveness of HDAC inhibitors, valproic acid, and suberoylanilide hydroxamic acid, in models of pulmonary arterial hypertension supports a therapeutic strategy based on HDAC inhibition in pulmonary arterial hypertension.
Recent Trends in Healthcare Utilization Among Children and Adolescents With Hypertension in the United States
Authors: Tran Cheryl L. , Ehrmann Brett J. , Messer Kassandra L. , Herreshoff Emily , Kroeker Amber , Wickman Larysa , Song Peter , Kasper Nicole , Gipson Debbie S.
Published: June 2012

The objective of this study was to evaluate the healthcare utilization of hospitalized children with hypertension. The Healthcare Cost and Utilization Project Kids' Inpatient Database, years 1997, 2000, 2003, and 2006, was used to identify hypertension hospitalizations. We examined the association of patient and hospital characteristics on hypertension charges. Data from each cohort year were used to analyze trends in charges. We found that 71282 pediatric hypertension hospitalizations generated $3.1 billion in total charges from 1997 to 2006. Approximately 68% were 10 to 18 years old, 55% were boys, and 47% were white. Six percent of claims with a diagnosis code for hypertension also had a diagnosis code for end-stage renal disease or renal transplant. The frequency of hypertension discharges increased over time (
P
=0.02 for each of age groups 2–9 years and 2–18 years;
P
=0.03 for age group 10–18 years), as well as the fraction of inpatient charges attributed to hypertension (
P
<0.0001). Length of stay and end-stage renal disease were associated with increases in hospitalization associated charges (
P
<0.0001 and
P
=0.03, respectively). During the 10-year study period, the frequency of hypertension-associated hospitalizations was increasing across all of the age groups, and the fraction of charges related to hypertension was also increasing. The coexisting condition of end-stage renal disease resulted in a significant increase in healthcare charges.
Timing of Aneurysm Treatment After Subarachnoid Hemorrhage
Authors: Dorhout Mees Sanne M. , Molyneux Andrew J. , Kerr Richard S. , Algra Ale , Rinkel Gabriel J.E.
Published: June 2012

Background and Purpose—

The ideal timing of coiling or clipping after aneurysmal subarachnoid hemorrhage is unknown. Within the International Subarachnoid Aneurysm Trial we assessed differences in incidence of delayed cerebral ischemia and clinical outcome between different timings of treatment.

Methods—

The treated 2106 patients randomized to coiling or clipping were divided into 4 categories: treatment <2 days, on days 3 to 4, on days 5 to 10, and >10 days after the hemorrhage. ORs with 95% CI were calculated with logistic regression analysis for delayed cerebral ischemia, poor outcome at 2 months, and 1 year for the different timing categories, with treatment <2 days as reference. Analyses were performed for all patients, and for coiled and clipped patients separately, and were adjusted for baseline characteristics.

Results—

Adjusted ORs of delayed cerebral ischemia for treatment on days 5 to 10 were 1.18 (95% CI, 0.91–1.53) for all patients, 1.68 (95% CI, 1.17–2.43) after coiling, and 0.79 (95% CI, 0.54–1.16) after clipping. ORs for poor outcome at 2 months were 1.16 (95% CI, 0.89–1.50) for treatment (clipping and coiling combined) at 3 to 4 days, 1.39 (95% CI, 1.08–1.80) for treatment at 5 to 10 days, and 1.84 (95% CI, 1.36–2.51) for treatment >10 days. ORs for coiled and clipped patients separately were in the same range. Results for outcome at 1 year were similar.

Conclusions—

Our results support the current practice for early aneurysm treatment in subarachnoid hemorrhage patients. The risk for poor outcome was highest when treatment was performed after day 10; postponing treatment in patients who are eligible for treatment between days 5 to 10 after subarachnoid hemorrhage is not recommended.
Intensive Versus Subcutaneous Insulin in Patients With Hyperacute Stroke
Authors: Rosso Charlotte , Corvol Jean-Christophe , Pires Christine , Crozier Sophie , Attal Yohan , Jacqueminet Sophie , Deltour Sandrine , Multlu Gurkan , Leger Anne , Meresse Isabelle , Payan Christine , Dormont Didier , Samson Yves
Published: June 2012

Background and Purpose—

Intensive insulin therapy (IIT) has not yet proven its efficacy on stroke prognosis or in the reduction of MRI infarct growth. The INSULINFARCT study aims at determining in patients with hyperacute stroke whether IIT, with a better control of poststroke hyperglycemia, would reduce subsequent MRI infarct growth than usual care with subcutaneous insulin.

Methods—

One hundred eighty patients with MRI-proven ischemic stroke and with National Institutes of Health Stroke Scale from 5 to 25 at admission (<6 hours) were randomized to receive IIT or usual subcutaneous insulin for 24 hours. Admission hyperglycemia was not required for recruitment. Control MRI and 3-month follow-up (with functional outcome and serious adverse events) were planned. The primary objective was to detect a difference in the proportion of patients with mean capillary glucose test <7 mmol/L during 24 hours. The secondary objective was to investigate whether IIT would reduce infarct growth. The analysis was planned in intention-to-treat. Patients with >3 missing capillary glucose test were excluded (n=4).

Results—

The proportion of patients with mean capillary glucose test <7 mmol/L in the first 24 hours was higher in the IIT group (95.4% [83 of 87] versus 67.4% [60 of 89];
P
<0.0001). The infarct growth was lower in the subcutaneous insulin group (median, 10.8 cm
3
; 95% CI, 6.5–22.4 versus 27.9 cm
3
; 14.6–40.7; 60% of increase;
P
=0.04). The 3-month functional outcome (45.6% [41 of 90] versus 45.6% [41 of 90]), death (15.6% [14 of 90] versus 10% [9 of 90]), and serious adverse events (38.9% [35 of 90] versus 35.6% [32 of 90]) were similar in the subcutaneous insulin and IIT group.

Conclusion—

The IIT regimen improved glucose control in the first 24 hours of stroke but was associated with larger infarct growths. IIT cannot be recommended in hyperacute ischemic stroke.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00472381.
Patterns of CO2 Variability from Global Satellite Data
Authors: Ruzmaikin Alexander , Aumann Hartmut H. , Pagano Thomas S.
Published: June 2012

The authors present an analysis of the global midtropospheric CO2 retrieved for all-sky (clear and cloudy) conditions from measurements by the Atmospheric Infrared Radiation Sounder on board the Aqua satellite in 2003–09. The global data coverage allows the identification of the set of CO2 spatial patterns and their time variability by applying principal component analysis and empirical mode decomposition. The first, dominant pattern represents 93% of the variability and exhibits the linear trend of 2 ± 0.2 ppm yr−1, as well as annual and interannual dependencies. The single-site record of CO2 at Mauna Loa compares well with variability of this pattern. The first principal component is phase shifted relative to the Southern Oscillation, indicating a causative relationship between the atmospheric CO2 and ENSO. The higher-order patterns show regional details of CO2 distribution and display the semiannual oscillation. The CO2 distributions are compared with the distribution of two major characteristics of air transport: the vertical velocity and potential temperature surfaces at the same height. In agreement with modeling, CO2 concentration closely traces the potential temperature surfaces (isentropes) in middle and high latitudes. However, its vertical transport in the tropics, where these surfaces are mostly horizontal, is suppressed. The results are in agreement with the previous results on annual and interannual CO2 time variability obtained by using the network flask data. This knowledge of the global CO2 spatial patterns can be useful in climate analyses and potentially in the challenging task of connecting CO2 sources and sinks with its distribution in the atmosphere.
Clock Genes Show Circadian Rhythms in Salivary Glands
Authors: Zheng L. , Seon Y.J. , McHugh J. , Papagerakis S. , Papagerakis P.
Published: June 2012

Circadian rhythms are endogenous self-sustained oscillations with 24-hour periods that regulate diverse physiological and metabolic processes through complex gene regulation by “clock” transcription factors. The oral cavity is bathed by saliva, and its amount and content are modified within regular daily intervals. The clock mechanisms that control salivary production remain unclear. Our objective was to evaluate the expression and periodicity of clock genes in salivary glands. Real-time quantitative RT-PCR, in situ hybridization, and immunohistochemistry were performed to show circadian mRNA and protein expression and localization of key clock genes ( Bmal1, Clock, Per1, and Per2), ion and aqua channel genes ( Ae2a, Car2, and Aqp5), and salivary gland markers. Clock gene mRNAs and clock proteins were found differentially expressed in the serous acini and duct cells of all major salivary glands. The expression levels of clock genes and Aqp5 showed regular oscillatory patterns under both light/dark and complete-dark conditions. Bmla1 overexpression resulted in increased Aqp5 expression levels. Analysis of our data suggests that salivary glands have a peripheral clock mechanism that functions both in normal light/dark conditions and in the absence of light. This finding may increase our understanding of the control mechanisms of salivary content and flow.
Examining the Impacts of Development Patterns on Flooding on the Gulf of Mexico Coast
Authors: Brody Samuel , Kim Heeju , Gunn Joshua
Published: June 2012

This article addresses this understudied aspect of development patterns and community resiliency by examining a five-year record of insured flood loss claims across 144 counties and parishes fringing the Gulf of Mexico. Linear regression models are employed to isolate the effects of five different development patterns on observed flood losses from 2001 to 2005 while controlling for multiple contextual variables. A novel approach is taken to measuring development form by using a series of landscape metrics usually reserved for ecological analysis. These measures enable the assessment of the form of the regional built environment with more specificity than has been possible in previous studies. Results indicate that more connected and concentrated development patterns lead to a reduction in the amount of observed flood losses. These findings illustrate the importance of regional planning and design for fostering flood-resilient communities.