bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Tumor Blood Flow, Angiogenesis, Tumor Hypoxia, and Aerobic Glycolysis
Authors: Østergaard Leif , Tietze Anna , Nielsen Thomas , Drasbek Kim Ryun , Mouridsen Kim , Jespersen Sune Nørhøj , Horsman Michael R.
Published: June 2013

Antiangiogenic therapies are being pursued as a means of starving tumors of their energy supply. Although numerous studies show that such therapies render tumors hypoxic, just as many studies have, surprisingly, shown improved tumor oxygenation. These contradicting findings challenge both the original rationale for antiangiogenic therapy and our understanding of the physiology of tissue oxygenation. The flow–diffusion equation, which describes the relation between blood flow and the extraction of freely diffusible molecules in tissue, was recently extended to take the heterogeneity of capillary transit times (CTH) into account. CTH is likely to be high in the chaotic microvasculature of a tumor, increasing the effective shunting of blood through its capillary bed. We review the properties of the extended flow–diffusion equation in tumor tissue. Elevated CTH reduces the extraction of oxygen, glucose, and cytotoxic molecules. The extent to which their net extraction is improved by antiangiogenic therapy, in turn, depends on the extent to which CTH is normalized by the treatment. The extraction of oxygen and glucose are affected to different extents by elevated CTH, and the degree of aerobic glycolysis—known as the Warburg effect—is thus predicted to represent an adaptation to the CTH of the local microvasculature. Cancer Res; 73(18); 5618–24. ©2013 AACR.
Postdiagnosis Cruciferous Vegetable Consumption and Breast Cancer Outcomes: A Report from the After Breast Cancer Pooling Project
Authors: Nechuta Sarah , Caan Bette J. , Chen Wendy Y. , Kwan Marilyn L. , Lu Wei , Cai Hui , Poole Elizabeth M. , Flatt Shirley W. , Zheng Wei , Pierce John P. , Shu Xiao Ou
Published: June 2013

Cruciferous vegetables are a major source of glucosinolate-derived bioactive compounds such as isothiocyanates, which have been shown in animal and in vitro studies to inhibit cancer growth and progression. Few studies have investigated cruciferous vegetable intake after diagnosis and breast cancer outcomes. Using data from the After Breast Cancer Pooling Project, which includes prospective data from U.S. and Chinese breast cancer survivors, we evaluated the association of cruciferous vegetables with breast cancer outcomes. Analyses included 11,390 women diagnosed with stage I–III invasive breast cancer (1990–2006) from four cohorts. Cruciferous vegetable intake (g/day) was assessed using food frequency questionnaires (mean of 22 months postdiagnosis). Study heterogeneity was evaluated by the Q statistic; hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using delayed-entry Cox regression models stratified by study. After a median follow-up of 9.0 years, 1,725 deaths and 1,421 recurrences were documented. In pooled analyses using study-specific quartiles, cruciferous vegetable intake was not associated with breast cancer outcomes, adjusting for known clinical prognostic factors and selected lifestyle factors. HRs (95% CIs) by increasing quartiles (reference = lowest quartile) were 1.08 (0.93–1.25), 1.01 (0.87–1.18), and 1.10 (0.95–1.28) for recurrence (Ptrend = 0.34) and 1.01 (0.88–1.15), 0.97 (0.84–1.11), and 0.99 (0.86–1.13) for total mortality (Ptrend = 0.84). No associations were observed for subgroups defined by estrogen receptor status, stage, or tamoxifen therapy. Cruciferous vegetable intake at approximately two years after diagnosis was not associated with recurrence or mortality. Our results do not support an association between postdiagnosis cruciferous vegetable intake and breast cancer outcomes. Cancer Epidemiol Biomarkers Prev; 22(8); 1451–6. ©2013 AACR.
Nimbolide, a Limonoid Triterpene, Inhibits Growth of Human Colorectal Cancer Xenografts by Suppressing the Proinflammatory Microenvironment
Authors: Gupta Subash C. , Prasad Sahdeo , Sethumadhavan Dhanya R. , Nair Mangalam S. , Mo Yin-Yuan , Aggarwal Bharat B.
Published: June 2013

Purpose: Extensive research over the past decade has revealed that the proinflammatory microenvironment plays a critical role in the development of colorectal cancer. Whether nimbolide, a limonoid triterpene, can inhibit the growth of colorectal cancer was investigated in the present study.

Experimental Design: The effect of nimbolide on proliferation of colorectal cancer cell lines was examined by MTT assay, apoptosis by caspase activation and poly-ADP ribose polymerase cleavage, NF-κB activation by DNA-binding assay, and protein expression by Western blotting. The effect of nimbolide on the tumor growth in vivo was examined in colorectal cancer xenografts in a nude mouse model.

Results: Nimbolide inhibited proliferation, induced apoptosis, and suppressed NF-κB activation and NF-κB–regulated tumorigenic proteins in colorectal cancer cells. The suppression of NF-κB activation by nimbolide was caused by sequential inhibition of IκB kinase (IKK) activation, IκBα phosphorylation, and p65 nuclear translocation. Furthermore, the effect of nimbolide on IKK activity was found to be direct. In vivo, nimbolide (at 5 and 20 mg/kg body weight), injected intraperitoneally after tumor inoculation, significantly decreased the volume of colorectal cancer xenografts. The limonoid-treated xenografts exhibited significant downregulation in the expression of proteins involved in tumor cell survival (Bcl-2, Bcl-xL, c-IAP-1, survivin, and Mcl-1), proliferation (c-Myc and cyclin D1), invasion (MMP-9, ICAM-1), metastasis (CXCR4), and angiogenesis (VEGF). The limonoid was found to be bioavailable in the blood plasma and tumor tissues of treated mice.

Conclusions: Our studies provide evidence that nimbolide can suppress the growth of human colorectal cancer through modulation of the proinflammatory microenvironment. Clin Cancer Res; 19(16); 4465–76. ©2013 AACR.
Localization, Not Important in All Tumor-Suppressing Properties: A Lesson Learnt from Scribble
Authors: Elsum Imogen A. , Humbert Patrick O.
Published: June 2013

Aberrant localization of proteins is increasingly being suggested as a causal player in epithelial cancers. Despite this, few studies have investigated how mislocalization of a protein can alter individual biological processes that contribute to cancer progression. Using Ras as a model of transformation, we investigate how localization of the polarity protein Scribble contributes to its tumor-suppressive properties. Wild-type Scribble has been shown to modulate Ras-mitogen-activated protein kinase (MAPK) transformation both in vitro and in vivo. By utilizing a construct that carries a mutation in the LRR domain of Scribble (Scribble P305L) resulting in a cytosolic rather than the usual membrane-bound localization, we report that discrete tumor suppressive properties of Scribble are differentially sensitive to the localization of Scribble. We find that although the Scribble P305L mislocalization mutant can no longer suppress Ras-MAPK-induced invasion or epithelial to mesenchymal transition phenotypes, mislocalized Scribble can still suppress anchorage-independent cell growth. This study illustrates that the manner in which protein mislocalization contributes to cancer is likely complex and highlights the need for careful interrogation as to how cell polarity protein mislocalization, its secondary consequences, and the mutations that give rise to their mislocalization may contribute to specific aspects of cancer progression.
Narrow Band Imaging with Magnifying Endoscopy for Peyer's Patches in Patients with Inflammatory Bowel Disease
Authors: Hiyama Satoshi , Iijima Hideki , Shinzaki Shinichiro , Mukai Akira , Inoue Takahiro , Shiraishi Eri , Kawai Syoichiro , Yamada Takuya , Nishida Tsutomu , Tsujii Masahiko , Takehara Tetsuo
Published: June 2013

Background/Aims: Peyer's patches (PPs) play a major role in mucosal immunity, but little is known about their alterations in patients with inflammatory bowel disease (IBD). We aimed to evaluate endoscopic changes of PPs in IBD patients using narrow band imaging with magnifying endoscopy (NBI-ME). Methods: Images of PPs using NBI-ME by ileocolonoscopy were consecutively collected. Existence of branch-like structures and the vessel occupancy in the dome lesions of PPs were analyzed. Appearance of the surrounding villi of the domes in PPs was evaluated using a ‘villi index' consisting of irregular formation, hyperemia, and altered vascular network pattern. Vascularity of PPs was immunohistologically analyzed by anti-CD34 antibody. Results: 17 patients with Crohn's disease (CD), 43 with ulcerative colitis (UC), and 23 healthy control subjects (HC) were analyzed. Both CD and UC patients had a high prevalence of having branch-like structures and significantly higher vascularity in the dome lesions than HC. The villi indices and vascular widths in the villi were significantly larger in CD and UC patients than in HC. Conclusions: Precise examination with NBI-ME characterized alteration of vascular structure in the dome and surrounding villi lesions of PPs not only in CD but also in UC patients.
KIT D816V Mutation-Positive Cell Fractions in Lesional Skin Biopsies from Adults with Systemic Mastocytosis
Authors: Kristensen Thomas , Broesby-Olsen Sigurd , Vestergaard Hanne , Bindslev-Jensen Carsten , Møller Michael Boe ,   on behalf of the Mastocytosis Centre, Odense University Hospital
Published: June 2013

Background: Most adults with systemic mastocytosis (SM) carry the somatic KIT D816V mutation, but the occurrence of the mutation in lesional skin remains to be characterized. Objective: To assess the distribution and fraction of KIT D816V mutation-positive cells in lesional skin. Methods: Lesional skin biopsies from 29 adults with SM were analysed using sensitive and quantitative qPCR KIT D816V mutation analysis. Results: The KIT D816V mutation was detected in skin in all cases. Highly similar mutation levels were observed in all patients with a median of 5% mutation-positive cells in the skin (range 1-23%). Conclusion: The KIT D816V mutation is consistently present in lesional skin in adults with SM. The low variation in mutation levels detected in lesional skin contrasts blood and bone marrow where mast cell (MC) progenitor and non-MC lineage involvement causes the mutation-positive cell fraction to be highly variable.
Impact of Mild Cognitive Impairment on Health-Related Quality of Life in Parkinson's Disease
Authors: Reginold William , Duff-Canning Sarah , Meaney Christopher , Armstrong Melissa J. , Fox Susan , Rothberg Brandon , Zadikoff Cindy , Kennedy Nancy , Gill David , Eslinger Paul , Marshall Fred , Mapstone Mark , Chou Kelvin L. , Persad Carol , Litvan Irene , Mast Benjamin , Tang-Wai David , Lang Anthony E. , Marras Connie
Published: June 2013

Background/Aims: To assess the impact of mild cognitive impairment (MCI) or cognitive decline on health-related quality of life (HR-QOL) in Parkinson's disease (PD). Methods: HR-QOL measured by the Parkinson Disease Quality of Life Questionnaire (PDQ-39), MCI according to Movement Disorder Society Task Force criteria and cognitive decline from premorbid baseline were assessed in non-demented PD patients at 6 movement disorder clinics. Results: Among 137 patients, after adjusting for education, gender, disease duration, and Movement Disorder Society Unified Parkinson's Disease Rating Scale total score, MCI was associated with worse scores within the PDQ-39 dimension of communication (p = 0.008). Subjects were divided into tertiles of cognitive decline from premorbid level. Scores in the dimension of stigma were worst in the second tertile of cognitive decline (p = 0.03). MCI was associated with worse social support scores in the second tertile of cognitive decline (p = 0.008). Conclusion: MCI and cognitive decline from premorbid baseline are associated with reduced HR-QOL in communication, stigma, and social support domains. The cognitive decline from premorbid baseline modifies the association between MCI and HR-QOL in PD and knowing both will allow a better appreciation of difficulties patients face in daily life.
Quantitative and Qualitative Spectral Domain Optical Coherence Tomography Analysis of Subretinal Deposits in Patients with Acute Central Serous Retinopathy
Authors: Landa Gennady , Barnett Jonathan A. , Garcia Patricia M.T. , Tai Katy W. , Rosen Richard B.
Published: June 2013

Purpose: To perform qualitative and quantitative analyses of subretinal protein deposits (PDs), seen in acute central serous retinopathy (CSR) patients, using high-resolution spectral domain optical coherence tomography (SD-OCT), in order to investigate whether the present PDs have any significant impact on best corrected visual acuity (BCVA). Methods: Patients diagnosed with acute CSR were included. Using SD-OCT, the following distances/heights were measured: central total retinal thickness, central neurosensory retinal thickness, the vertical and horizontal length of subfoveal subretinal fluid and subfoveal thickness of the PD layer, if present and could be measured. Results: Thirty-eight patients with acute CSR were included. A significant correlation was found between the subfoveal thickness of the PD layer and baseline/final visual acuities in the eyes (r = 0.60, p ≤ 0.001 and r = 0.45, p = 0.008, respectively). Conclusions: The thickness of subfoveal PDs at baseline appears to be an important parameter related to the BCVA and time of CSR resolution.
Submucosal Administration of OnabotulinumtoxinA in the Treatment of Neurogenic Detrusor Overactivity: Pilot Single-Centre Experience and Comparison with Standard Injection into the Detrusor
Authors: Šámal Vladimír , Mečl Jan , Šrám Jaroslav
Published: June 2013

Introduction: Apart from the standard intramural administration of botulinum neurotoxin A (BoNT/A) to the detrusor, intense research is taking place into new means of administration in view of the complex mechanism of action of BoNT/A. Methods: An open, randomised, prospective study was performed on a total of 23 patients with neurogenic detrusor overactivity. Following randomisation, patients were treated with 300 U of onabotulinumtoxinA (onaBoNT/A) in either the submucosa or the detrusor. Urodynamic examinations were carried out, and a bladder diary was kept both prior to and 12 weeks after the treatment. All patients stopped taking anticholinergics 1 week prior to the treatment. Results: In both the submucosa and detrusor groups, we recorded a significant improvement in the monitored urodynamic parameters and significant decreases in the frequency of urinary incontinence episodes following the treatment. A comparison of the two groups showed no significant difference between the two forms of application, with the exception of voided volume (p = 0.007). Conclusion: A comparison of the two administration methods did not show any significant difference between onaBoNT/A administration to the submucosa and to the detrusor. Thus, the submucosal injection of onaBoNT/A represents an equally effective approach for its administration to patients.
Residual Dizziness after Successful Repositioning Maneuvers for Idiopathic Benign Paroxysmal Positional Vertigo
Authors: Teggi Roberto , Quaglieri Silvia , Gatti Omar , Benazzo Marco , Bussi Mario
Published: June 2013

Objective: To establish a possible causal factor for residual dizziness (RD) after successful repositioning maneuvers in patients with benign paroxysmal positional vertigo (BPPV). Materials and Method: Ninety consecutive patients with idiopathic BPPV were treated with repositioning maneuvers, and the rate of RD was assessed as well as clinical data. Posturography and assessment of anxiety levels were performed on patients reporting RD. Results were compared with a control group of BPPV patients of the sample after repositioning maneuvers and without RD. Results: Twenty-eight subjects (31.1%) reported RD on the second day after successful repositioning maneuvers. The mean duration of RD was 11.6 ± 3.9 days. Patients with RD presented a higher duration of BPPV (14.1 vs. 10.9 days, p = 0.01). A correlation was demonstrated between the duration of BPPV and duration of RD (p < 0.01). Subjects with RD presented increased body sways, above all in eyes-closed conditions. Conclusion: RD is mainly correlated with duration of vertigo in BPPV patients. Anxiety was demonstrated to play a role in increased body sways.
Rapid Detection of Aneuploidy and Unbalanced Chromosomal Rearrangements by Subtelomeric Multiplex Ligation-Dependent Probe Amplification in Fetuses with Congenital Heart Disease
Authors: Wang Jing , Liu Zhen , Liu Hongqian , Li Nana , Li Shengli , Chen Xinlin , Lin Yuan , Wang He , Zhu Jun , Liu Shanling
Published: June 2013

Objective: To validate multiplex ligation-dependent probe amplification (MLPA) with subtelomeric probe mixes as a tool for diagnosis of aneuploidy and unbalanced terminal chromosomal rearrangements in fetuses with congenital heart disease. Methods: A prospective study of 117 fetuses found to have structural heart defects by ultrasound at 17-40 weeks' gestation. MLPA with P036E and P070B probe mixes was performed and compared to traditional karyotyping by cell culture and to findings of quantitative fluorescence-polymerase chain reaction (QF-PCR). Results: MLPA was able to define the fetal karyotype in 99% of cases whereas cell culture only defined the karyotype in 64% of cases. Consequently, the overall number of chromosomal abnormalities that were detected increased. The majority of these affected chromosomes, 21, 18, 13, X or Y, were also confirmed by QF-PCR. Two (5%) cases had atypical aneuploidy that was confirmed by MLPA but not by QF-PCR. In 4 cases, structural rearrangements or mosaicism were not detected by MLPA. Conclusions: Subtelomeric MLPA may be a valuable adjunct to QF-PCR and/or conventional cytogenetics for the investigation of chromosomal abnormalities in fetuses with congenital heart disease.
DNA Enzyme ED5 Depletes Egr-1 and Inhibits Neointimal Hyperplasia in Rats
Authors: Wang Tai-Ran , Yang Guang , Liu Gui-Nan
Published: June 2013

Objectives: Depletion of early growth response factor-1 (Egr-1) by a DNA enzyme, ED5, inhibits neointimal hyperplasia (NH) following vascular injury by an unknown mechanism. The aim of this study was to characterize the effects of ED5 in a rat carotid injury model in order to elucidate the mechanism by which ED5 inhibits NH. Methods: ED5 was transfected into the arterial wall of Wistar rats using FuGENE6 transfection reagent following artery balloon injury. Hematoxylin and eosin staining, immunohistochemistry, real-time reverse transcription polymerase chain reaction and Western blotting analysis were used to characterize the response to ED5. Results: NH decreased significantly in the ED5- plus FuGENE6-treated rats (p < 0.05) compared with the control groups, and this was accompanied by a reduced inflammatory response. Egr-1 mRNA and protein levels were significantly decreased in the ED5-treated group, as expected. The decrease in Egr-1 was accompanied by decreases in the mRNA and protein levels of PDGF-BB, Cyclin D1, CDK4, MCP-1, and ICAM-1 (p < 0.05). Conclusions: Transfection of the Egr-1-specific synthetic DNA enzyme ED5 significantly reduced NH after injury in rats, at least in part, as a result of decreased expression of downstream proliferative genes such as PDGF-BB, Cyclin D1, CDK4, and the inflammatory factors MCP-1 and ICAM-1.
Antiplatelet Drugs Are a Risk Factor for Esophageal Mucosal Injury
Authors: Sugimoto Mitsushige , Uotani Takahiro , Nishino Masafumi , Yamade Mihoko , Sahara Shu , Yamada Takanori , Osawa Satoshi , Sugimoto Ken , Umemura Kazuo , Watanabe Hiroshi , Miyajima Hiroaki , Furuta Takahisa
Published: June 2013

Background: In esophagus whether antiplatelet drugs, such as low-dose aspirin (LDA) and clopidogrel, induce mucosal injury by pH changes or by acid reflux is unclear. We designed to clarify which mechanism was responsible. Methods: In study 1, 80 patients taking LDA and 80 age- and sex-matched subjects who underwent endoscopy for dyspeptic symptoms or for a health check-up were evaluated the endoscopic incidence of esophageal mucosal injury and severity. In study 2, 35 healthy subjects were treated with LDA 100 mg (regimen A), and then 20 randomly selected subjects were dosed clopidogrel 75 mg (regimen C), LDA/clopidogrel (regimen AC), or LDA/clopidogrel/rabeprazole 10 mg for 7 days. Subjects underwent endoscopy and 24-hour pH measurements on day 7. Results: In study 1, the prevalence of esophageal injury in LDA patients was 40.0%, significantly higher than in non-LDA subjects (25.0%, p = 0.042). In study 2, significant increases in incidence of injury were observed with regimens A (45.8%) and AC (50.0%), but not with C (20.0%), on day 7. Among subjects in whom pH was >5.0 and <4.0 for less than 40% of time, none developed esophageal injury. Conclusions: LDA caused esophageal injury in half of patients and volunteers. Acid-inhibitory drugs effectively prevented the development of LDA-induced, not clopidogrel, esophageal injury.
Frequency and Phenotype of Human Circulating and Intrahepatic Natural Killer Cell Subsets Is Differentially Regulated according to Stage of Chronic Liver Disease
Authors: Zimmermann Henning Wolfgang , Mueller Jan Robert , Seidler Sebastian , Luedde Tom , Trautwein Christian , Tacke Frank
Published: June 2013

Background/Aims: Experimental liver injury models have indicated that natural killer (NK) cells are critical regulators of inflammation and fibrosis. However, data on NK cells and subsets in patients with liver diseases are limited. We thus comprehensively characterized peripheral and hepatic NK cell subsets in patients with chronic liver diseases (CLDs) of different etiologies and fibrosis stages. Methods: NK cells and other lymphocyte populations were characterized by FACS in 189 CLD patients (71 non-cirrhosis, 118 cirrhosis) and 153 healthy controls in blood and liver biopsies (n = 40). Results: In contrast to other lymphocyte subsets, circulating NK cells were generally reduced in CLD patients. Patients with fibrosis displayed a distinct increase of CD16- NK cells in blood and of the CD16+ NK cell subset in liver. Patients with cirrhosis had overall lymphopenia, including reduced peripheral NK cells. Most pronounced shifts in NK cell subsets in blood and liver were found in cholestatic and autoimmune CLDs. Blood NK cells and subsets correlated with liver function, and inversely with fibrosis markers and inflammatory cytokines. Conclusions: The close association of human NK cells with disease severity and the intrahepatic accumulation of CD16+ NK cells in early fibrosis favor the concept of beneficial NK cell functions in hepatofibrogenesis.
Relation between Parametric Change of the Workload and Prefrontal Cortex Activity during a Modified Version of the ‘Rock, Paper, Scissors' Task
Authors: Yamauchi Yoshiki , Kikuchi Senichiro , Miwakeichi Fumikazu , Matsumoto Kenji , Nishida Masaki , Ishiguro Makio , Watanabe Eiju , Kato Satoshi
Published: June 2013

Background/Aims: Modified rock, paper, scissors (RPS) tasks have previously been used in neuroscience to investigate activity of the prefrontal cortex (PFC). In this study, we investigated hemodynamic changes in the PFC using near-infrared spectroscopy (NIRS) during a modified RPS task in which each subject's successful performance rate was equalized; the workload was increased parametrically in order to reveal the resulting pattern of PFC activation. Methods: The subjects were 20 healthy adults. During RPS, the player uses hand gestures to represent rock, paper, and scissors. Rock beats scissors, paper beats rock, and scissors beats paper. In the modified RPS task, the player is instructed to lose intentionally against the computer hand; the computer goes first and the player follows. The interstimulus interval (ISI) level was adjusted with 11 steps. If the level rose, the ISI decreased and the workload increased parametrically. The maximal level (maxLv: the shortest ISI and the biggest workload) in which a subject could perform the task correctly was determined for every subject during rehearsal of the task prior to the experiment. Lowering the level from the maxLv made the task easier. Hemodynamic changes were measured by NIRS over 4 task levels (maxLv-3, maxLv-2, maxLv-1 and maxLv). Results: The hemodynamic changes in the left lateral PFC and bilateral Brodmann area 6 rose significantly with the increase in workload and presented a linear trend. Conclusion: These results suggest that PFC activation may linearly increase with increased workload during a modified RPS task in which successful performance rates of subjects are equalized.
Mindfulness-Based Stress Reduction for Older Adults: Effects on Executive Function, Frontal Alpha Asymmetry and Immune Function
Authors: Moynihan Jan A. , Chapman Benjamin P. , Klorman Rafael , Krasner Michael S. , Duberstein Paul R. , Brown Kirk Warren , Talbot Nancy L.
Published: June 2013

Background/Aims: Mindfulness-based stress reduction (MBSR) has enhanced cognition, positive emotion, and immunity in younger and middle-aged samples; its benefits are less well known for older persons. Here we report on a randomized controlled trial of MBSR for older adults and its effects on executive function, left frontal asymmetry of the EEG alpha band, and antibody response. Methods: Older adults (n = 201) were randomized to MBSR or waiting list control. The outcome measures were: the Trail Making Test part B/A (Trails B/A) ratio, a measure of executive function; changes in left frontal alpha asymmetry, an indicator of positive emotions or approach motivation; depression, mindfulness, and perceived stress scores, and the immunoglobulin G response to a protein antigen, a measure of adaptive immunity. Results: MBSR participants had a lower Trails B/A ratio immediately after intervention (p < 0.05); reduced shift to rightward frontal alpha activation after intervention (p = 0.03); higher baseline antibody levels after intervention (p < 0.01), but lower antibody responses 24 weeks after antigen challenge (p < 0.04), and improved mindfulness after intervention (p = 0.023) and at 21 weeks of follow-up (p = 0.006). Conclusions: MBSR produced small but significant changes in executive function, mindfulness, and sustained left frontal alpha asymmetry. The antibody findings at follow-up were unexpected. Further study of the effects of MBSR on immune function should assess changes in antibody responses in comparison to T-cell-mediated effector functions, which decline as a function of age.
No Association between a Polymorphism in the Serotonin Receptor 2B (HTR2B) Gene and Personality Traits in Healthy Japanese Subjects
Authors: Tsuchimine Shoko , Taniguchi Takeshi , Sugawara Norio , Kaneda Ayako , Yasui-Furukori Norio
Published: June 2013

Aim: The brain neurotransmitter serotonin affects many aspects of human behavior, including personality traits. Because the serotonin receptor 2B (HTR2B) gene has recently been associated with impulsivity, we investigated the potential association between the rs10194776 and Q20* polymorphism in the HTR2B gene and personality traits in healthy subjects. Methods: A total of 1,171 healthy Japanese subjects were enrolled in this study. Their personality traits were evaluated using the Temperament and Character Inventory (TCI), and the rs10194776 and Q20* genotype was determined using real-time polymerase chain reaction. Results: There was a significant main effect of the rs10194776 polymorphism on harm avoidance and self-directedness in females (p = 0.037 and p = 0.043, respectively). However, these differences were insignificant after a Bonferroni correction. Subjects carrying the minor allele of the Q20* polymorphism were nonexistent. Conclusion: The results of the present study suggest that the HTR2B polymorphism is not likely to be associated with personality traits, including novelty seeking and impulsivity.
Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models
Authors: Wit J.M. , Ranke M.B. , Albertsson-Wikland K. , Carrascosa A. , Rosenfeld R.G. , Van Buuren S. , Kristrom B. , Schoenau E. , Audi L. , Hokken-Koelega A.C.S. , Bang P. , Jung H. , Blum W.F. , Silverman L.A. , Cohen P. , Cianfarani S. , Deal C. , Clayton P.E. , de Graaff L. , Dahlgren J. , Kleintjens J. , Roelants M.
Published: June 2013

The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.
Early Communicative Development in Two Cultures: A Comparison of the Communicative Environments of Children from Two Cultures
Authors: Lieven Elena , Stoll Sabine
Published: June 2013

The nature of young children's communicative environment has been central to theoretical debates about the importance of innate and environmental factors in the development of communication and language. In this paper, we explore aspects of the communicative development and environment of young children growing up in two very different cultures, one in a village of eastern Nepal and the other in a rural area of Western Germany. We analysed longitudinal video recordings of 6 children from each culture in naturalistic settings, at age-matched time points over a period of 8 months. Four children were 8 months old at the outset of the study, 4 were 2 years and 2 months old, and 4 were 3 years old. There were major differences between cultures in the number of adults and children present during the recordings, with other children playing an increasingly important role for the older children in the Nepal recordings. We found no difference between cultures in the onset of pointing and imitation or of reaching, requesting and offering, indicating that these behaviours may be part of a human-specific timetable for socio-cognitive development. We also found that imitation by both the target children and those around them was strictly limited to the youngest group in both cultures. This suggests that imitation may be very important for early development in the prelinguistic phase, while around the age of 2, with the child's developing competence, other ways of interacting take over. The theoretical implications of our results are discussed with reference to the roles of child-intrinsic and environmental factors in the developmental process.
Rhesus Macaques Recognize Unique Multimodal Face-Voice Relations of Familiar Individuals and Not of Unfamiliar Ones
Authors: Habbershon Holly M. , Ahmed Sarah Z. , Cohen Yale E.
Published: June 2013

Communication signals in nonhuman primates are inherently multimodal. However, for laboratory-housed monkeys, there is relatively little evidence in support of the use of multimodal communication signals in individual recognition. Here, we used a preferential-looking paradigm to test whether laboratory-housed rhesus monkeys could ‘spontaneously' (i.e., in the absence of operant training) use multimodal communication stimuli to discriminate between known conspecifics. The multimodal stimulus was a silent movie of 2 monkeys vocalizing and an audio file of the vocalization from one of the monkeys in the movie. We found that the gaze patterns of the monkeys that knew the individuals in the movie were reliably biased toward the individual that did not produce the vocalization. In contrast, there was not a systematic gaze pattern for the monkeys that did not know the individuals in the movie. These data are consistent with the hypothesis that laboratory-housed rhesus macaques can recognize and distinguish between conspecifics based on auditory and visual communication signals.
Exosome-Derived miRNAs and Cellular miRNAs Activate Innate Immunity
Authors: Mobergslien Anne , Sioud Mouldy
Published: June 2013

Circulating exosome-containing small RNAs have been demonstrated in vitro to be taken up by recipient cells and to alter gene expression through RNA interference. Here, we show that exosomes purified from various cancer cell lines as well as gel-purified exosomal and cellular miRNAs can induce pro-inflammatory cytokine expression in human peripheral blood mononuclear cells. Thus, circulating miRNAs may trigger innate immunity via pathogen recognition receptors, a new miRNA-activated pathway that merits some consideration.
Role of Extracellular Vesicles in De Novo Mineralization
Authors: New Sophie E. P. , Aikawa Elena
Published: June 2013

Extracellular vesicles are membrane micro/nanovesicles secreted by many cell types into the circulation and the extracellular milieu in physiological and pathological conditions. Evidence suggests that extracellular vesicles, known as matrix vesicles, play a role in the mineralization of skeletal tissue, but emerging ultrastructural and in vitro studies have demonstrated their contribution to cardiovascular calcification as well. Cells involved in the progression of cardiovascular calcification release active vesicles capable of nucleating hydroxyapatite on their membranes. This review discusses the role of extracellular vesicles in cardiovascular calcification and elaborates on this additional mechanism of calcification as an alternative pathway to the currently accepted mechanism of biomineralization via osteogenic differentiation.
Perivascular Delivery of Encapsulated Mesenchymal Stem Cells Improves Postischemic Angiogenesis Via Paracrine Activation of VEGF-A
Authors: Katare Rajesh , Riu Federica , Rowlinson Jonathan , Lewis Andrew , Holden Rachel , Meloni Marco , Reni Carlotta , Wallrapp Christine , Emanueli Costanza , Madeddu Paolo
Published: June 2013

Objective—

To test the therapeutic activity of perivascular transplantation of encapsulated human mesenchymal stem cells (MSCs) in an immunocompetent mouse model of limb ischemia.

Approach and Results—

CD1 mice underwent unilateral limb ischemia, followed by randomized treatment with vehicle, alginate microbeads (MBs), MB-encapsulated MSCs (MB-MSCs), or MB-MSCs engineered with glucagon-like peptide-1. Treatments were applied directly in the perivascular space around the femoral artery. Laser Doppler and fluorescent microsphere assessment of blood flow showed a marked improvement of perfusion in the MB-MSCs and MB-MSCs engineered with glucagon-like peptide-1 groups, which was associated with increased foot salvage particularly in MB-MSCs engineered with glucagon-like peptide-1–treated mice. Histological analysis revealed increased capillary and arteriole density in limb muscles of the 2 MSC groups. Furthermore, MB-MSCs engineered with glucagon-like peptide-1 and, to a lesser extent, MB-MSC treatment increased functional arterial collaterals alongside the femoral artery occlusion. Analysis of expressional changes in ischemic muscles showed that MB-MSC transplantation activates a proangiogenic signaling pathway centered on vascular endothelial growth factor A. In contrast, intramuscular MB-MSCs caused inflammatory reaction, but no improvement of reparative vascularization. Importantly, nonencapsulated MSCs were ineffective either by intramuscular or perivascular route.

Conclusions—

Perivascular delivery of encapsulated MSCs helps postischemic reperfusion. This novel biological bypass method might be useful in patients not amenable to conventional revascularization approaches.
Usefulness of Exercise Test and Myocardial Perfusion–Gated Single Photon Emission Computed Tomography to Improve the Prediction of Major Events
Authors: Candell-Riera Jaume , Ferreira-González Ignacio , Marsal Josep R. , Aguadé-Bruix Santiago , Cuberas-Borrós Gemma , Pujol Paula , Romero-Farina Guillermo , Nazarena-Pizzi María , de León Gustavo , Castell-Conesa Joan , García-Dorado David
Published: June 2013

Background—

The incremental prognostic value of myocardial perfusion–gated single photon emission computed tomography (MPGS) compared with exercise test has not yet been properly evaluated.

Methods and Results—

Five thousand six hundred seventy-two consecutive patients with known or suspected coronary disease undergoing exercise MPGS between 1997 and 2007 were included. Three-year predictive models for total death and death from cardiovascular causes or acute myocardial infarction (ie, major cardiovascular events [MCE]) were built using Cox-regression modeling, including only the clinical information. Then the exercise and MPGS information was sequentially added. The added discriminative ability of exercise test information and MPGS was assessed by net reclassification improvement and integrated discrimination improvement. The increase in predictive ability of exercise information for death and MCE was high as assessed by net reclassification improvement (0.199 and 0.263) and integrated discrimination improvement (0.042 and 0.021). The only variable of MPGS associated with total death was ejection fraction (hazard ratio, 0.84; 95% confidence interval, 0.79–0.89;
P
<0.001). Global stress ischemic score emerged as an additional variable associated with MCE (hazard ratio, 1.07; 95% confidence interval, 1.02–1.12;
P
=0.007). Adding MPGS information barely improved the prognostic value for total death (net reclassification improvement, 0.017; integrated discrimination improvement, 0.013), but it increased for MCE (net reclassification improvement, 0.122; integrated discrimination improvement, 0.033).

Conclusions—

Adding MPGS information to exercise information does not improve prediction of total death, although it allows a more accurate prediction of MCE.
Early New Diffusion-Weighted Imaging Lesions Appear More Often in Stroke Patients With a Multiple Territory Lesion Pattern
Authors: Braemswig Tim Bastian , Usnich Tatiana , Albach Fredrik N. , Brunecker Peter , Grittner Ulrike , Scheitz Jan F. , Fiebach Jochen B. , Nolte Christian H.
Published: June 2013

Background and Purpose—

New diffusion-weighted imaging (DWI) lesions are common in patients with acute ischemic stroke. They are associated with an initial nonsingle lesion pattern. Previous studies have not analyzed this association in detail. We differentiated nonsingle lesions in 1 vascular supply territory only (scattered lesion pattern) from nonsingle lesions in ≥2 vascular supply territory (multiple territory lesion -pattern).

Methods—

Patients with an acute ischemic stroke underwent 3 MRI (3T) examinations: on admission, on the following day, and 4 to 7 days after symptom onset. First, DWI lesions were delineated manually by raters blinded to clinical details. Second, DWI images were coregistered and analyzed visually for new hyperintensities. The initial lesion pattern was categorized as single, scattered, or multiple territory.

Results—

Of 340 patients enrolled, 43% had a single lesion pattern, 40% had a scattered lesion pattern, and 17% had a multiple territory lesion pattern. In multivariable analysis, the categorical variable lesion pattern was independently associated with new DWI lesions (odds ratio
multiple territory lesion pattern
, 3.64 [95% confidence interval, 1.75–7.58]; odds ratio
scattered lesion pattern
, 1.96 [95% confidence interval, 1.09–3.56]). Patients with multiple territory lesion pattern had significantly more often diabetes mellitus, and their new lesions were more often located remotely from the initial area of hypoperfusion compared with patients with scattered lesion pattern.

Conclusion—

Lesion pattern on initial image is an independent risk factor for new DWI lesions. The risk for new DWI lesions is highest in patients with multiple territory lesion pattern.
Campanula martinii (Campanulaceae), a new species from northern Italy
Authors: FENAROLI FRANCO , PISTARINO ANNALAURA , PERUZZI LORENZO , CELLINESE NICO
Published: June 2013

Campanula martinii a new species in the C. rotundifolia species complex, is here described. C. martinii is seemingly endemic to dolomitic cliffs and rocky places of the Prealps in Lombardia and Trentino-Alto Adige (northern Italy). The plants are robust with long hypogeal stolons, papillose ovary and patent to reflexed calyx teeth. This species is hexaploid with chromosome number 2n = 102. The taxonomic and phylogenetic placement of the new species is briefly discussed.
Impact of Rossby Wave Breaking on U.S. West Coast Winter Precipitation during ENSO Events
Authors: Ryoo Ju-Mee , Kaspi Yohai , Waugh Darryn W. , Kiladis George N. , Waliser Duane E. , Fetzer Eric J. , Kim Jinwon
Published: June 2013

This study demonstrates that water vapor transport and precipitation are largely modulated by the intensity of the subtropical jet, transient eddies, and the location of wave breaking events during the different phases of ENSO. Clear differences are found in the potential vorticity (PV), meteorological fields, and trajectory pathways between the two different phases. Rossby wave breaking events have cyclonic and anticyclonic regimes, with associated differences in the frequency of occurrence and the dynamic response. During La Niña, there is a relatively weak subtropical jet allowing PV to intrude into lower latitudes over the western United States. This induces a large amount of moisture transport inland ahead of the PV intrusions, as well as northward transport to the west of a surface anticyclone. During El Niño, the subtropical jet is relatively strong and is associated with an enhanced cyclonic wave breaking. This is accompanied by a time-mean surface cyclone, which brings zonal moisture transport to the western United States. In both (El Niño and La Niña) phases, there is a high correlation (>0.3–0.7) between upper-level PV at 250 hPa and precipitation over the west coast of the United States with a time lag of 0–1 days. Vertically integrated water vapor fluxes during El Niño are up to 70 kg m−1 s−1 larger than those during La Niña along the west coast of the United States. The zonal and meridional moist static energy flux resembles wave vapor transport patterns, suggesting that they are closely controlled by the large-scale flows and location of wave breaking events during the different phase of ENSO.
A Physical Basis for the Probabilistic Prediction of the Accumulated Tropical Cyclone Kinetic Energy in the Western North Pacific
Authors: Kim Hye-Mi , Lee Myong-In , Webster Peter J. , Kim Dongmin , Yoo Jin Ho
Published: June 2013

The relationship between El Niño–Southern Oscillation (ENSO) and tropical storm (TS) activity over the western North Pacific Ocean is examined for the period from 1981 to 2010. In El Niño years, TS genesis locations are generally shifted to the southeast relative to normal years and the passages of TSs tend to recurve to the northeast. TSs of greater duration and more intensity during an El Niño summer induce an increase of the accumulated tropical cyclone kinetic energy (ACE). Based on the strong relationship between the TS properties and ENSO, a probabilistic prediction for seasonal ACE is investigated using a hybrid dynamical–statistical model. A statistical relationship is developed between the observed ACE and large-scale variables taken from the ECMWF seasonal forecast system 4 hindcasts. The ACE correlates positively with the SST anomaly over the central to eastern Pacific and negatively with the vertical wind shear near the date line. The vertical wind shear anomalies over the central and western Pacific are selected as predictors based on sensitivity tests of ACE predictive skill. The hybrid model performs quite well in forecasting seasonal ACE with a correlation coefficient between the observed and predicted ACE at 0.80 over the 30-yr period. A relative operating characteristic analysis also indicates that the ensembles have significant probabilistic skill for both the above-normal and below-normal categories. By comparing the ACE prediction over the period from 2003 to 2011, the hybrid model appears more skillful than the forecast from the Tropical Storm Risk consortium.
Who Votes in Latin America? A Test of Three Theoretical Perspectives
Authors: Carreras Miguel , Castañeda-Angarita Néstor
Published: June 2013

Previous studies of electoral participation in Latin America have focused on the political and institutional factors that influence country differences in the aggregate level of turnout. This article provides a theoretical and empirical examination of the individual-level factors that have an impact on citizens’ propensity to vote. We test three theoretical perspectives that have been used to explain electoral participation in industrialized democracies (voters’ resources, voters’ motivations, and mobilization networks). Using a series of logistic and hierarchical models, we demonstrate that the demographic characteristics of voters (age and education) and citizens’ insertion in mobilizing networks (civic organizations and the working place) are strong predictors of electoral participation in Latin America. Our analysis also confirms the importance of contextual and institutional variables to explain turnout in the region.
Rival Strategies of Validation
Authors: Seawright Jason , Collier David
Published: June 2013

The challenge of finding appropriate tools for measurement validation is an abiding concern in political science. This article considers four traditions of validation, using examples from cross-national research on democracy: the levels-of-measurement approach, structural-equation modeling with latent variables, the pragmatic tradition, and the case-based method. Methodologists have sharply disputed the merits of alternative traditions. We encourage scholars—and certainly analysts of democracy—to pay more attention to these disputes and to consider strengths and weaknesses in the validation tools they adopt. An online appendix summarizes the evaluation of six democracy data sets from the perspective of alternative approaches to validation. The overall goal is to open a new discussion of alternative validation strategies.
Therapeutic Engagement and Posttreatment Substance Use in Adolescent TC Clients
Authors: Gunter Whitney D. , Abdel-Salam Sami
Published: June 2013

The problem of adolescent drug use places a huge toll on society and a heavy burden on the criminal justice system. Despite the ability of therapeutic communities (TCs) to lower drug relapse, a great deal remains unknown in terms of how the process of treatment actually works for adolescents. Using data collected as part of the Drug Abuse Treatment Outcomes Studies–Adolescents, this study examines the direct and indirect relationship between therapeutic engagement and posttreatment substance use. Though there are few direct effects of therapeutic engagement on substance use, findings suggest that those more engaged in treatment are more likely to complete treatment and, therefore, less likely to use substances. This suggests that instruments that evaluate therapeutic engagement are important in assessing involvement in treatment, and that programming designed to engage the adolescents in TC treatment should be utilized to reduce the risk of posttreatment relapse.