bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilevel model estimation of age-dependent individual-specific trajectories for left ventricular echocardiographic indexes in an asymptomatic elderly cohort
Authors: Wang Yu-hong , Jiang Yu-ping , Luo Shan-shun , Qiao Fang-fang , Han Hui
Published: January 2012

Few studies have been performed on the individual-specific trajectory of left ventricular aging as assessed by echocardiography in an asymptomatic elderly cohort. In the present study, a representative cohort of elderly men, who were long-term asymptomatic for cardiovascular issues, were selected from an ongoing observational aging study. Annual echocardiographic data were used to establish an age-dependent hierarchical model. Based on two-level linear regression results, four echocardiographic indexes [left ventricular mass (LVmass; −1.872 g/yr), posterior ventricular wall thickness (−0.048 mm/yr), fraction shortening (0.097/yr), and transmitral peak A velocity (−0.006 m·s−1·yr−1)] changed significantly with increasing age and were age- and subject-dependent. The most characterized results of the study were the significant, age-related, within-individual variances in echocardiographic results, which were observed using the likelihood ratio test at an occasion-dependent level. Of these, fluctuated amplitudes of two systolic variables [i.e., LVmass (con/age = −0.012 ± 0.004; P = 0.0007) and fraction shortening (con/age = −0.001 ± 0.004; P = 0.05)] were significantly attenuated with increasing age within individuals. On the other hand, the age-related variability of four diastolic Doppler variables [i.e., peak A velocity (con/age = 0.003 ± 0.002; P = 0.0009), peak E velocity (con/age = 0.004 ± 0.003; P = 0.01), E/A ratio (con/age = 0.007 ± 0.003; P = 0.0002), and deceleration time of E wave (con/age = 0.025 ± 0.007; P < 0.0001)] significantly increased with increasing age within individuals. The age-related individual variability of left ventricular indexes observed in this continuous asymptomatic cohort may reflect the mechanism of preclinical, individualized heart aging. In conclusion, successfully fitted multilevel models were applied as a valuable tool to determine the mechanism of individual cardiac aging in the elderly.
Long-term use of high-heeled shoes alters the neuromechanics of human walking
Authors: Cronin Neil J. , Barrett Rod S. , Carty Christopher P.
Published: January 2012

Human movement requires an ongoing, finely tuned interaction between muscular and tendinous tissues, so changes in the properties of either tissue could have important functional consequences. One condition that alters the functional demands placed on lower limb muscle-tendon units is the use of high-heeled shoes (HH), which force the foot into a plantarflexed position. Long-term HH use has been found to shorten medial gastrocnemius muscle fascicles and increase Achilles tendon stiffness, but the consequences of these changes for locomotor muscle-tendon function are unknown. This study examined the effects of habitual HH use on the neuromechanical behavior of triceps surae muscles during walking. The study population consisted of 9 habitual high heel wearers who had worn shoes with a minimum heel height of 5 cm at least 40 h/wk for a minimum of 2 yr, and 10 control participants who habitually wore heels for less than 10 h/wk. Participants walked at a self-selected speed over level ground while ground reaction forces, ankle and knee joint kinematics, lower limb muscle activity, and gastrocnemius fascicle length data were acquired. In long-term HH wearers, walking in HH resulted in substantial increases in muscle fascicle strains and muscle activation during the stance phase compared with barefoot walking. The results suggest that long-term high heel use may compromise muscle efficiency in walking and are consistent with reports that HH wearers often experience discomfort and muscle fatigue. Long-term HH use may also increase the risk of strain injuries.
Pyramidal tract neurons receptive to different forelimb joints act differently during locomotion
Authors: Stout Erik E. , Beloozerova Irina N.
Published: January 2012

During locomotion, motor cortical neurons projecting to the pyramidal tract (PTNs) discharge in close relation to strides. How their discharges vary based on the part of the body they influence is not well understood. We addressed this question with regard to joints of the forelimb in the cat. During simple and ladder locomotion, we compared the activity of four groups of PTNs with somatosensory receptive fields involving different forelimb joints: 1) 45 PTNs receptive to movements of shoulder, 2) 30 PTNs receptive to movements of elbow, 3) 40 PTNs receptive to movements of wrist, and 4) 30 nonresponsive PTNs. In the motor cortex, a relationship exists between the location of the source of afferent input and the target for motor output. On the basis of this relationship, we inferred the forelimb joint that a PTN influences from its somatosensory receptive field. We found that different PTNs tended to discharge differently during locomotion. During simple locomotion shoulder-related PTNs were most active during late stance/early swing, and upon transition from simple to ladder locomotion they often increased activity and stride-related modulation while reducing discharge duration. Elbow-related PTNs were most active during late swing/early stance and typically did not change activity, modulation, or discharge duration on the ladder. Wrist-related PTNs were most active during swing and upon transition to the ladder often decreased activity and increased modulation while reducing discharge duration. These data suggest that during locomotion the motor cortex uses distinct mechanisms to control the shoulder, elbow, and wrist.
Stability limits modulate whole-body motor learning
Authors: Manista Gregory C. , Ahmed Alaa A.
Published: January 2012

Our daily movements exert forces upon the environment and also upon our own bodies. To control for these forces, movements performed while standing are usually preceded by anticipatory postural adjustments (APAs). This strategy is effective at compensating for an expected perturbation, as it reduces the need to compensate for the perturbation in a reactive manner. However, it can also be risky if one anticipates the incorrect perturbation, which could result in movements outside stability limits and a loss of balance. Here, we examine whether the margin for error defined by these stability limits affects the amount of anticipation. Specifically, will one rely more on anticipation when the margin for error is lower? Will the degree of anticipation scale with the margin for error? We took advantage of the asymmetric stability limits (and margins for error) present in the sagittal plane during upright stance and investigated the effect of perturbation direction on the magnitude of APAs. We also compared anticipatory postural control with the anticipatory control observed at the arm. Standing subjects made reaching movements to multiple targets while grasping the handle of a robot arm. They experienced forward or backward perturbing forces depending on the target direction. Subjects learned to anticipate the forces and generated APAs. Although subjects had the biomechanical capacity to adapt similarly in the forward and backward directions, APAs were reduced significantly in the backward direction, which had smaller stability limits and a smaller margin for error. Interestingly, anticipatory control produced at the arm, where stability limits are not as relevant, was not affected by perturbation direction. These results suggest that stability limits modulate anticipatory control, and reduced stability limits lead to a reduction in anticipatory postural control.
Tonic NMDA receptor-mediated current in prefrontal cortical pyramidal cells and fast-spiking interneurons
Authors: Povysheva Nadezhda V. , Johnson Jon W.
Published: January 2012

Tonically activated neuronal currents mediated by N-methyl-d-aspartate receptors (NMDARs) have been hypothesized to contribute to normal neuronal function as well as to neuronal pathology resulting from excessive activation of glutamate receptors (e.g., excitotoxicity). Whereas cortical excitatory cells are very vulnerable to excitotoxic insult, the data regarding resistance of inhibitory cells (or interneurons) are inconsistent. Types of neurons with more pronounced tonic NMDAR current potentially associated with the activation of extrasynaptic NMDARs could be expected to be more vulnerable to excessive activation by glutamate. In this study, we compared tonic activation of NMDARs in excitatory pyramidal cells and inhibitory fast-spiking interneurons in prefrontal cortical slices. We assessed tonic NMDAR current by measuring holding current shift as well as noise reduction following NMDAR blockade after removal of spontaneous glutamate release. In addition, we compared NMDAR miniature excitatory postsynaptic currents (EPSCs) in both cell types. We have demonstrated for the first time that tonic NMDAR currents are present in inhibitory fast-spiking interneurons. We found that the magnitude of tonic NMDAR current is similar in pyramidal cells and fast-spiking interneurons, and that quantal release of glutamate does not significantly impact tonic NMDAR current.
Plastin Family of Actin-Bundling Proteins: Its Functions in Leukocytes, Neurons, Intestines, and Cancer
Authors: Shinomiya Hiroto
Published: January 2012

Sophisticated regulation of the actin cytoskeleton by a variety of actin-binding proteins is essential for eukaryotic cells to perform their diverse functions. The plastin (also know, as fimbrin) protein family belongs to actin-bundling proteins, and the protein family is evolutionarily conserved and expressed in yeast, plant, and animal cells. Plastins are characterized by EF-hand Ca2+-binding domains and actin-binding domains and can cross-link actin filaments into higher-order assemblies like bundles. Three isoforms have been identified in mammals. T-plastin is expressed in cells from solid tissues, such as neurons in the brain. I-plastin expression is restricted to intestine and kidney; the isoform plays a vital role in the function of absorptive epithelia in these organs. L-plastin is expressed in hematopoietic cell lineages and in many types of cancer cells; the isoform is thus considered to be a useful biomarker for cancer.
Cyclosporine: A Review
Authors: Tedesco Dustin , Haragsim Lukas
Published: January 2012

The discovery and use of cyclosporine since its inception into clinical use in the late 1970s has played a major role in the advancement of transplant medicine. While it has improved rates of acute rejection and early graft survival, data on long-term survival of renal allografts is less convincing. The finding of acute reversible nephrotoxicity and nephrotoxicity in nonrenal transplants has since led to the widely accepted view that there is a chronic more irreversible component to this agent as well. Since that time, there has been intense interest in finding protocols which seek to minimize and even avoid the use of calcineurin inhibitors altogether. We seek to review cyclosporine in terms of its mechanism of action, pathophysiologic, and histologic features associated with acute and chronic nephrotoxicity and recent studies looking to avoid its toxic side effects.
Exploring Diversification and Genome Size Evolution in Extant Gymnosperms through Phylogenetic Synthesis
Authors: Burleigh J. Gordon , Barbazuk W. Brad , Davis John M. , Morse Alison M. , Soltis Pamela S.
Published: January 2012

Gymnosperms, comprising cycads, Ginkgo, Gnetales, and conifers, represent one of the major groups of extant seed plants. Yet compared to angiosperms, little is known about the patterns of diversification and genome evolution in gymnosperms. We assembled a phylogenetic supermatrix containing over 4.5 million nucleotides from 739 gymnosperm taxa. Although 93.6% of the cells in the supermatrix are empty, the data reveal many strongly supported nodes that are generally consistent with previous phylogenetic analyses, including weak support for Gnetales sister to Pinaceae. A lineage through time plot suggests elevated rates of diversification within the last 100 million years, and there is evidence of shifts in diversification rates in several clades within cycads and conifers. A likelihood-based analysis of the evolution of genome size in 165 gymnosperms finds evidence for heterogeneous rates of genome size evolution due to an elevated rate in Pinus.
Fracture Detection in Traumatic Pelvic CT Images
Authors: Wu Jie , Davuluri Pavani , Ward Kevin R. , Cockrell Charles , Hobson Rosalyn , Najarian Kayvan
Published: January 2012

Fracture detection in pelvic bones is vital for patient diagnostic decisions and treatment planning in traumatic pelvic injuries. Manual detection of bone fracture from computed tomography (CT) images is very challenging due to low resolution of the images and the complex pelvic structures. Automated fracture detection from segmented bones can significantly help physicians analyze pelvic CT images and detect the severity of injuries in a very short period. This paper presents an automated hierarchical algorithm for bone fracture detection in pelvic CT scans using adaptive windowing, boundary tracing, and wavelet transform while incorporating anatomical information. Fracture detection is performed on the basis of the results of prior pelvic bone segmentation via our registered active shape model (RASM). The results are promising and show that the method is capable of detecting fractures accurately.
From Spinal Central Pattern Generators to Cortical Network: Integrated BCI for Walking Rehabilitation
Authors: Cheron G. , Duvinage M. , De Saedeleer C. , Castermans T. , Bengoetxea A. , Petieau M. , Seetharaman K. , Hoellinger T. , Dan B. , Dutoit T. , Sylos Labini F. , Lacquaniti F. , Ivanenko Y.
Published: January 2012

Success in locomotor rehabilitation programs can be improved with the use of brain-computer interfaces (BCIs). Although a wealth of research has demonstrated that locomotion is largely controlled by spinal mechanisms, the brain is of utmost importance in monitoring locomotor patterns and therefore contains information regarding central pattern generation functioning. In addition, there is also a tight coordination between the upper and lower limbs, which can also be useful in controlling locomotion. The current paper critically investigates different approaches that are applicable to this field: the use of electroencephalogram (EEG), upper limb electromyogram (EMG), or a hybrid of the two neurophysiological signals to control assistive exoskeletons used in locomotion based on programmable central pattern generators (PCPGs) or dynamic recurrent neural networks (DRNNs). Plantar surface tactile stimulation devices combined with virtual reality may provide the sensation of walking while in a supine position for use of training brain signals generated during locomotion. These methods may exploit mechanisms of brain plasticity and assist in the neurorehabilitation of gait in a variety of clinical conditions, including stroke, spinal trauma, multiple sclerosis, and cerebral palsy.
Is the Time Necessary to Obtain Preoperative Stabilization a Predictive Index of Outcome in Neonatal Congenital Diaphragmatic Hernia?
Authors: Gentili Andrea , De Rose Rosina , Iannella Elisa , Bacchi Reggiani Maria Letizia , Lima Mario , Baroncini Simonetta
Published: January 2012

Background. The study aims to verify if the time of preoperative stabilization (≤24 or >24 hours) could be predictive for the severity of clinical condition among patients affected by congenital diaphragmatic hernia.Methods. 55 of the 73 patients enrolled in the study achieved presurgical stabilization and underwent surgical correction. Respiratory and hemodynamic indexes, postnatal scores, the need for advanced respiratory support, the length of HFOV, tracheal intubation, PICU, and hospital stay were compared between patients reaching stabilization in ≤24 or >24 hours.Results. Both groups had a 100% survival rate. Neonates stabilized in ≤24 hours are more regular in the postoperative period and had an easier intensive care path; those taking >24 hours showed more complications and their care path was longer and more complex.Conclusions. The length of preoperative stabilization does not affect mortality, but is a valid parameter to identify difficulties in survivors’ clinical pathway.
Collagen Cross-Linking: Current Status and Future Directions
Authors: Hovakimyan Marine , Guthoff Rudolf F. , Stachs Oliver
Published: January 2012

Collagen cross-linking (CXL) using UVA light and riboflavin (vitamin B2) was introduced as a clinical application to stabilize the cornea by inducing cross-links within and between collagen fibers. CXL has been investigated extensively and has been shown clinically to arrest the progression of keratoconic or post-LASIK ectasia. With its minimal cost, simplicity, and proven positive clinical outcome, CXL can be regarded as a useful approach to reduce the number of penetrating keratoplasties performed. Small case series have also indicated that CXL is beneficial in corneal edema by reducing stromal swelling behavior and in keratitis by inhibiting pathogen growth. Despite these encouraging results, CXL remains a relatively new method that is potentially associated with complications. Aspects such as side effects and recurrence rates have still to be elucidated. In light of the growing interest in CXL, our paper summarizes present knowledge about this promising approach. We have intentionally endeavored to include the more relevant studies from the recent literature to provide an overview of the current status of CXL.
Is Freezing of Gait in Parkinson's Disease a Result of Multiple Gait Impairments? Implications for Treatment
Authors: Plotnik Meir , Giladi Nir , Hausdorff Jeffrey M.
Published: January 2012

Several gait impairments have been associated with freezing of gait (FOG) in patients with Parkinson's disease (PD). These include deteriorations in rhythm control, gait symmetry, bilateral coordination of gait, dynamic postural control and step scaling. We suggest that these seemingly independent gait features may have mutual interactions which, during certain circumstances, jointly drive the predisposed locomotion system into a FOG episode. This new theoretical framework is illustrated by the evaluation of the potential relationships between the so-called “sequence effect”, that is, impairments in step scaling, and gait asymmetry just prior to FOG. We further discuss what factors influence gait control to maintain functional gait. “Triggers”, for example, such as attention shifts or trajectory transitions, may precede FOG. We propose distinct categories of interventions and describe examples of existing work that support this idea: (a) interventions which aim to maintain a good level of locomotion control especially with respect to aspects related to FOG; (b) those that aim at avoiding FOG “triggers”; and (c) those that merely aim to escape from FOG once it occurs. The proposed theoretical framework sets the stage for testable hypotheses regarding the mechanisms that lead to FOG and may also lead to new treatment ideas.
Effects of Iron Concentration Level in Extracting Solutions from Contaminated Soils on the Determination of Zinc by Flame Atomic Absorption Spectrometry with Two Background Correctors
Authors: Waterlot Christophe , Pelfrêne Aurélie , Douay Francis
Published: January 2012

Zinc and iron concentrations were determined after digestion, water, and three-step sequential extractions of contaminated soils. Analyses were carried out using flame absorption spectrometry with two background correctors: a deuterium lamp used as the continuum light source (D2method) and the high-speed self-reversal method (HSSR method). Regarding the preliminary results obtained with synthetic solutions, the D2method often emerged as an unsuitable configuration for compensating iron spectral interferences. In contrast, the HSSR method appeared as a convenient and powerful configuration and was tested for the determination of zinc in contaminated soils containing high amounts of iron. Simple, fast, and interference-free method, the HSSR method allows zinc determination at the ppb level in the presence of large amounts of iron with high stability, sensitivity, and reproducibility of results. Therefore, the HSSR method is described here as a promising approach for monitoring zinc concentrations in various iron-containing samples without any pretreatment.
On Programmed Cell Death inPlasmodium falciparum: Status Quo
Authors: Engelbrecht Dewaldt , Durand Pierre Marcel , Coetzer Thérèsa Louise
Published: January 2012

Conflicting arguments and results exist regarding the occurrence and phenotype of programmed cell death (PCD) in the malaria parasitePlasmodium falciparum. Inconsistencies relate mainly to the number and type of PCD markers assessed and the different methodologies used in the studies. In this paper, we provide a comprehensive overview of the current state of knowledge and empirical evidence for PCD in the intraerythrocytic stages ofP. falciparum. We consider possible reasons for discrepancies in the data and offer suggestions towards more standardised investigation methods in this field. Furthermore, we present genomic evidence for PCD machinery inP. falciparum. We discuss the potential adaptive or nonadaptive role of PCD in the parasite life cycle and its possible exploitation in the development of novel drug targets. Lastly, we pose pertinent unanswered questions concerning the PCD phenomenon inP. falciparumto provide future direction.
Fundamental Issues in Manufacturing Photovoltaic Modules Beyond the Current Generation of Materials
Authors: Alapatt G. F. , Singh R. , Poole K. F.
Published: January 2012

Many methods to improve the solar cell’s efficiency beyond current generation of bulk and thin film of photovoltaic (PV) devices have been reported during the last five decades. Concepts such as multiple exciton generations (MEG), carrier multiplication (CM), hot carrier extraction, and intermediate band solar cells have fundamental flaws, and there is no experimental evidence of fabricating practical higher efficiency solar cells based on the proposed concepts. To take advantages of quantum features of nanostructures for higher performance PV devices, self-assembly-based bottom-up processing techniques are not suitable for manufacturing due to inherent problems of variability, defects, reliability, and yield. For processing nanostructures, new techniques need to be invented with the features of critical dimensional control, structural homogeneity, and lower cost of ownership as compared to the processing tools used in current generations of bulk and thin-film solar cells.
Time and Temperature Dependence of CdS Nanoparticles Grown in a Polystyrene Matrix
Authors: Antolini F. , Burresi E. , Stroea L. , Morandi V. , Ortolani L. , Accorsi G. , Blosi M.
Published: January 2012

Luminescent CdS nanocrystals embedded in a polystyrene matrix were successfully prepared. The in situ growth of CdS QDs was realized by thermal treatment of Cd bis(thiolate)/polymer foil at different times and temperatures (240°C and 300°C) of annealing, in order to evaluate their influence on the quantum dots growth process. As a general trend, the increasing of time and temperature of annealing induces a rise of the CdS nanocrystals size into the polymeric matrix. The size distribution, morphology, and structure of the CdS nanoparticles were analysed with HRTEM and XRD experiments. UV‐Vis and PL data are strongly size‐dependent and were used to investigate the particles′ growth process, too. The CdS nanoparticles behavior in solution indicated a general trend of QDs to aggregation. This predisposition was clearly displayed by DLS measurements.
Proteomic Analysis ofTrypanosoma cruziEpimastigotes Subjected to Heat Shock
Authors: Pérez-Morales Deyanira , Lanz-Mendoza Humberto , Hurtado Gerardo , Martínez-Espinosa Rodrigo , Espinoza Bertha
Published: January 2012

Trypanosoma cruziis exposed to sudden temperature changes during its life cycle. Adaptation to these variations is crucial for parasite survival, reproduction, and transmission. Some of these conditions may change the pattern of genetic expression of proteins involved in homeostasis in the course of stress treatment. In the present study, the proteome ofT. cruziepimastigotes subjected to heat shock and epimastigotes grow normally was compared by two-dimensional gel electrophoresis followed by mass spectrometry for protein identification. Twenty-four spots differing in abundance were identified. Of the twenty-four changed spots, nineteen showed a greater intensity and five a lower intensity relative to the control. Several functional categories of the identified proteins were determined: metabolism, cell defense, hypothetical proteins, protein fate, protein synthesis, cellular transport, and cell cycle. Proteins involved in the interaction with the cellular environment were also identified, and the implications of these changes are discussed.
A Two‐Step Method to Synthesize BaSn(OH)6 Crystalline Nanorods and Their Thermal Decomposition to Barium Stannate
Authors: Wu Xiaohong , Lv Gang , Hu Xiaoyan , Tang Yiwen
Published: January 2012

A novel two‐step technique is introduced to synthesize BaSn(OH)6 nanorods. The method involves the preparation of precursor Na2Sn(OH)6 crystals in aqueous solution via hydrothermal method and the ion‐exchange reaction between Na2Sn(OH)6 crystals and Ba2+ solution that followed, assisted by ultrasonic treatment. The BaSn(OH)6 nanorods array are formed due to the split of plate‐formed Na2Sn(OH)6 during the ion‐exchange treatment. The influence of the surfactant on the growth of the one‐dimensional (1D) BaSn(OH)6 nanostructures is investigated. In addition, the powder BaSnO3 has been obtained by thermal treatment at 450°C for 5 h under inert gas protecting condition using BaSn(OH)6 nanorods as precursor. The 1D shape of BaSn(OH)6 was retained after thermal treatment.
PRAS40 Is a Functionally Critical Target for EWS Repression in Ewing Sarcoma
Authors: Huang Lin , Nakai Yuji , Kuwahara Iku , Matsumoto Ken
Published: January 2012

Ewing sarcoma family tumors (ESFT) are highly aggressive and highly metastatic tumors caused by a chromosomal fusion between the Ewing sarcoma protein (EWS) with the transcription factor FLI-1. However, expression of the EWS/FLI-1 chimeric oncogene by itself is insufficient for carcinogenesis, suggesting that additional events are required. Here, we report the identification of the Akt substrate PRAS40 as an EWS target gene. EWS negatively regulates PRAS40 expression by binding the 3′ untranslated region in PRAS40 mRNA. ESFT cell proliferation was suppressed by treatment with an Akt inhibitor, and ESFT cell proliferation and metastatic growth were suppressed by siRNA-mediated PRAS40 knockdown. Furthermore, PRAS40 knockdown was sufficient to reverse an increased cell proliferation elicited by EWS knockdown. In support of a pathologic role for PRAS40 elevation in EFST, we documented inverse protein levels of EWS and PRAS40 in ESFT cells. Together, our findings suggest that PRAS40 promotes the development of ESFT and might therefore represent a novel therapeutic target in this aggressive disease. Cancer Res; 72(5); 1260–9. ©2012 AACR.
Kaposi Sarcoma Herpesvirus Promotes Endothelial-to-Mesenchymal Transition through Notch-Dependent Signaling
Authors: Gasperini Paola , Espigol-Frigole Georgina , McCormick Peter J. , Salvucci Ombretta , Maric Dragan , Uldrick Thomas S. , Polizzotto Mark N. , Yarchoan Robert , Tosato Giovanna
Published: January 2012

Endothelial-to-mesenchymal transition (EndMT) is now widely considered a pivotal contributor to cancer progression. In this study, we show that the Kaposi's sarcoma (KS)–associated herpesvirus (KSHV) is a sufficient cause of EndMT, potentially helping to explain the aggressiveness of KS that occurs commonly in AIDS patients. Upon KSHV infection, primary dermal microvascular endothelial cells lost expression of endothelial markers and acquired expression of mesenchymal markers, displaying new invasive and migratory properties along with increased survival. KSHV activated Notch-induced transcription factors Slug and ZEB1, and canonical Notch signaling was required for KSHV-induced EndMT. In contrast, KSHV did not utilize the TGFβ signaling pathway, which has also been linked to EndMT. Within KS lesions, KSHV-infected spindle cells displayed features compatible with KSHV-induced EndMT including a complex phenotype of endothelial and mesenchymal properties, Notch activity, and nuclear ZEB1 expression. Our results show that KSHV engages the EndMT program to increase the invasiveness and survival of infected endothelial cells, traits that likely contribute to viral persistence and malignant progression. One important implication of our findings is that therapeutic approaches to disrupt the Notch pathway may offer novel approaches for KS treatment. Cancer Res; 72(5); 1157–69. ©2012 AACR.
The 14-3-3σ Tumor Suppressor Has Multiple Functions in ErbB2-Induced Breast Cancer
Authors: Hynes Nancy E. , Smirnova Tatiana
Published: January 2012

Ling and colleagues demonstrated that loss of the conditional 14-3-3σ allele results in accelerated HER2/ERBB2-driven mammary tumorigenesis and metastasis. This study underscores the role of 14-3-3σ as a potent tumor suppressor in ERBB2-driven tumor initiation and progression. Cancer Discovery; 2(1); 19–22. ©2012 AACR.

Commentary on Ling et al., p. 68.
Endoscopic Findings in Mantle Cell Lymphoma with Gastrointestinal Tract Involvement
Authors: Kim Jung Ha , Jung Hyun Wook , Kang Ki Joo , Min Byung-Hoon , Lee Jun Haeng , Chang Dong Kyung , Kim Young Ho , Son Hee Jung , Rhee Poong-Lyul , Kim Jae J. , Rhee Jong Chul , Kim Seok Jin , Kim Won Seog , Ko Young Hyeh , Kim Jin Yong
Published: January 2012

Background and Aims: Mantle cell lymphoma (MCL) of the gastrointestinal (GI) tract is a rare disease with a poor prognosis. The aim of this study was to determine clinical and endoscopic characteristics of patients with GI MCL. Methods: Clinical features of 19 patients with GI MCL were reviewed along with the endoscopic findings on 27 anatomical lesions. Results: The initial presenting symptoms were abdominal pain (n = 7, 36.8%), GI tract bleeding (n = 5, 26.3%), dyspnea (n = 2, 10.5%), indigestion (n = 1, 5.3%), diarrhea (n = 1, 5.3%), cervical lymphadenopathy (n = 1, 5.3%), tonsilar mass (n = 1, 5.3%), and no symptoms (n = 1, 5.3%). On endoscopy, in 19 patients with 27 lesions, the anatomic locations of the lesions were: stomach, n = 2 (10.5%); stomach and colon, n = 7 (36.8%); terminal ileum and colon, n = 1 (5.3%); colon, n = 9 (47.4%). There was 1 fungating case (3.7%), 4 ulcerative cases (14.8%), 9 infiltrative cases (33.3%), and 13 polypoid cases (48.1%). Conclusions: The endoscopic findings in GI MCL are variable, with common presenting manifestations of abdominal pain and GI bleeding.
Techniques of Extracorporeal Cytokine Removal: A Systematic Review of the Literature
Authors: Atan Rafidah , Crosbie David , Bellomo Rinaldo
Published: January 2012

Background and Aims: Attempts at achieving cytokine homeostasis include blood purification to deliver cytokine removal. Assessment of ex vivo studies for optimal operating conditions is a vital step. Methods: We conducted a systematic search for ex vivo studies on cytokine removal using known modalities of extracorporeal circulation. We selected 29 articles and analyzed data according to clearance, sieving coefficient, ultrafiltrate concentration and percentage removal. Results: We identified four main techniques for cytokine removal: standard techniques, high cut-off (HCO) techniques, adsorption techniques and combined plasma filtration adsorption. HCO hemofiltration (HCO/HF) showed greatest consistency in cytokine removal among all approaches. Mean albumin clearance with HCO filters was 3.74 ml/min. Conclusion: Ex vivo data support the view that HCO/HF is the most consistently effective approach in terms of sieving and clearance. Further investigation of HCO/HF in randomized controlled trials in animal models and humans seems desirable.
Bmi-1 Promotes the Chemoresistance, Invasion and Tumorigenesis of Pancreatic Cancer Cells
Authors: Yin Tao , Wei Hongji , Leng Zhenwei , Yang Zhiyong , Gou Shanmiao , Wu Heshui , Zhao Gang , Hu Xiaoqing , Wang Chunyou
Published: January 2012

Background/Aims: The polycomb protein Bmi-1 plays oncogenic roles in various cancers. Here we aimed to investigate the contribution of Bmi-1 on the malignant behaviors of pancreatic cancer such as chemoresistance, invasion and tumorigenesis. Methods and Results: The MTT cell proliferation assay showed that shRNA mediated Bmi-1 knockdown and enhanced the chemosensitivity of pancreatic cancer cells to gemcitabine. The transwell invasion assay showed that Bmi-1 knockdown inhibited the invasion of pancreatic cancer cells in vitro. Notably, the reduced abilities of chemoresistance and invasion were associated with the transition from the mesenchymal phenotype to the epithelial phenotype of pancreatic cancer cells. Moreover, Bmi-1 knockdown led to the inhibition of the PI3K-Akt pathway and disrupted the sphere-forming abilities of pancreatic cancer cells. A nude mouse xenograft experiment demonstrated that pancreatic cancer cells depleted of Bmi-1 showed weak tumorigenicity in vivo. Conclusion: Our data suggest that Bmi-1 plays an important role in the progression of pancreatic cancer and represents a novel target for antitumor therapy of pancreatic cancer.
Prolonged Survival with Imatinib Mesylate Combined with Chemotherapy and Allogeneic Stem Cell Transplantation in de novo Ph+ Acute Myeloid Leukemia
Authors: Sun Jie , Wang Zhen , Luo Yi , Tan Yamin , Allan David S. , Huang He
Published: January 2012

Background: De novo Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) is a rare disease with a poor prognosis. Imatinib mesylate (IM) is the standard treatment for Ph+ chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia; however, its role in Ph+ AML has not been extensively investigated. Methods: Two patients aged of 46 and 19 years were diagnosed with de novo Ph+ AML according to the WHO Classification of Myeloid Neoplasms (2002) and the French-American-British (FAB) classification systems (1989). Cytogenetic analysis confirmed the presence of t(9;22). Standard RT-PCR was used to detect expression of the BCR-ABL1 fusion gene. Minimal residual disease was monitored by RQ-PCR for the BCR-ABL1/ABL ratio. Both patients received initial IM therapy combined with daunorubicin-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) and IM maintenance treatment after allo-HSCT. Results: Both patients achieved long-term disease-free survival with complete hematologic response, complete molecular response, and complete cytogenetic response for 44 and 48 months, respectively. Conclusions: Our cases indicate that IM combined with daunorubicin-based chemotherapy followed by allo-HSCT and IM maintenance treatment is associated with a favorable outcome for de novo Ph+ AML, especially when IM is used in an early phase of AML.
Audit of Physicians’ Adherence to the Antibiotic Policy Guidelines in Kuwait
Authors: Aly Nasser Y. , Omar Abeer A. , Badawy Dina A. , Al-Mousa Haifa H. , Sadek Ali A.
Published: January 2012

Objective: To audit physicians’ adherence to the local antibiotic policy guidelines in government hospitals in Kuwait. Materials and Methods: The study was a retrospective review of patient records in nine hospitals between July 1 and December 31, 2008. Clinical notes and medication charts of the latest hospital admissions were checked for antibiotic prescribing. On the audit form, aspects of the prescribed antibiotic were benchmarked to the hospital antibiotic policy guidelines to evaluate adherence. Results: Of 2,232 reviewed records, 1,112 (49.8%) patients had 1,528 antibiotic prescriptions. Patients who received antibiotics were significantly younger than those who did not (median age: 26.3 vs. 29.8 years, p < 0.001) and their hospital stay was significantly longer (median: 4 vs. 2 days, p < 0.001). The choice of an antibiotic was appropriate and matched the policy in 806 (52.7%) prescriptions. Of such appropriate antibiotics, adherence to route of administration was observed in 768/806 (95.3%), to dose in 758 (94%), to frequency in 746 (92.6%) and to duration in 608 (75.4%). Full adherence to all aspects of antibiotic choice, dose, route, frequency and duration was achieved in 464 (30.4%) prescriptions. In 382 (25%), the antibiotics administered were not indicated. Conclusion: There was low adherence to the local antibiotic policy guidelines. Physicians’ antibiotic prescribing practices should be optimized. Adherence to, and update of, the policy is recommended.
Twist Is a New Prognostic Marker for Renal Survival in Patients with Chronic Kidney Disease
Authors: Sun Shiren , Du Rui , Xia Lin , Sun Wenjuan , Zhai Ying , Yu Yan , Zhao Ali , Huang Chen , Ning Xiaoxuan , Wang Hanmin
Published: January 2012

Background/Aims: Our previous studies indicate that Twist plays important roles in hypoxia-induced tubular epithelial-mesenchymal transition and the development of kidney fibrosis in cellular and animal models. However, the expression and clinical significance of Twist in patients with chronic kidney disease are not clear. Methods: We analyzed the degree of expression and localization of Twist in renal biopsies from a wide variety of hypoxic kidney diseases and correlated their immunostaining scores with clinical and histologic parameters. In particular, we also retrospectively analyzed whether the degree of expression of Twist in the renal interstitium was correlated with renal survival. Results: Activated Twist was strongly expressed in tubular epithelial cell nuclei from the kidneys of patients with chronic kidney diseases, while little positive staining for Twist was found in the renal tubules of normal kidneys (p = 0.001). Twist protein in the tubulointerstitium was inversely correlated with estimated glomerular filtration rate (eGFR; r = –0.468, p = 0.029) and positively correlated with serum creatinine (r = 0.44, p = 0.045) and the percentage of tubulointerstitial fibrosis (r = 0.551, p = 0.000). Moreover, a high level of Twist was correlated with activation of HIF-1α expression and E-cadherin repression across all disease groups (p = 0.000, p = 0.000, respectively). By multivariate analysis, the experimental data show that the factors influencing renal survival were eGFR [relative risk (RR) 4.39 (95%CI 1.342, 14.393), p = 0.014] and the degree of expression of Twist [RR 3.43 (95% CI 1.098, 10.684), p = 0.034]. Conclusions: Our results raise the possibility that Twist activation is a common mechanism in the pathophysiology of a wide range of chronic hypoxic renal diseases and that Twist staining in renal biopsy specimens might provide a valuable histologic index of progression.
FOXL2 Impairment in Human Disease
Authors: Verdin Hannah , De Baere Elfride
Published: January 2012

FOXL2 encodes a forkhead transcription factor that plays important roles in the ovary during development and in post-natal, adult life. Here, we focus on the clinical consequences of FOXL2 impairment in human disease. In line with other forkhead transcription factors, its constitutional genetic defects and a somatic mutation lead to developmental disease and cancer, respectively. More than 100 unique constitutional mutations and regulatory defects have been found in blepharophimosis syndrome (BPES), a complex eyelid malformation associated (type I) or not (type II) with premature ovarian failure (POF). In agreement with the BPES phenotype, FOXL2 is expressed in the developing eyelids and in fetal and adult ovaries. Two knock-out mice and at least one natural animal model, the Polled Intersex Syndrome goat, are known. They recapitulate the BPES phenotype and have provided many insights into the ovarian pathology. Only a few constitutional mutations have been described in nonsyndromic POF. Moreover, a recurrent somatic mutation p.C134W was found to be specific for adult ovarian granulo-sa cell tumors. Functional studies investigating the consequences of FOXL2 mutations or regulatory defects have shed light on the molecular pathogenesis of the aforementioned conditions, and contributed considerably to genotype-phenotype correlations. Recently, a conditional knock-out of Foxl2 in the mouse induced somatic transdifferentiation of ovary into testis in adult mice, suggesting that Foxl2 has an anti-testis function in the adult ovary. This changed our view on the ovary and testis as terminally differentiated organs in adult mammals. Finally, this might have potential implications for the understanding and treatment of frequent conditions such as POF and polycystic ovary syndrome.
Relationship Between Vein Graft Failure and Subsequent Clinical Outcomes After Coronary Artery Bypass Surgery
Authors: Lopes Renato D. , Mehta Rajendra H. , Hafley Gail E. , Williams Judson B. , Mack Michael J. , Peterson Eric D. , Allen Keith B. , Harrington Robert A. , Gibson C. Michael , Califf Robert M. , Kouchoukos Nicholas T. , Ferguson T. Bruce , Alexander John H.
Published: January 2012

Background—

Vein graft failure (VGF) is common after coronary artery bypass graft surgery, but its relationship with long-term clinical outcomes is unknown. In this retrospective analysis, we examined the relationship between VGF, assessed by coronary angiography 12 to 18 months after coronary artery bypass graft surgery, and subsequent clinical outcomes.

Methods and Results—

Using the Project of Ex Vivo Vein Graft Engineering via Transfection IV (PREVENT IV) trial database, we studied data from 1829 patients who underwent coronary artery bypass graft surgery and had an angiogram performed up to 18 months after surgery. The main outcome measure was death, myocardial infarction, and repeat revascularization through 4 years after angiography. VGF occurred in 787 of 1829 patients (43%). Clinical follow-up was completed in 97% of patients with angiographic follow-up. The composite of death, myocardial infarction, or revascularization occurred more frequently among patients who had any VGF compared with those who had none (adjusted hazard ratio, 1.58; 95% confidence interval, 1.21–2.06;
P
=0.008). This was due mainly to more frequent revascularization with no differences in death (adjusted hazard ratio, 1.04; 95% confidence interval, 0.71–1.52;
P
=0.85) or death or myocardial infarction (adjusted hazard ratio, 1.08; 95% confidence interval, 0.77–1.53;
P
=0.65).

Conclusions—

VGF is common after coronary artery bypass graft surgery and is associated with repeat revascularization but not with death and/or myocardial infarction. Further investigations are needed to evaluate therapies and strategies for decreasing VGF to improve outcomes in patients undergoing coronary artery bypass graft surgery.
Characterizing and Identifying Risk for Falls in the LEAPS Study
Authors: Tilson Julie K. , Wu Samuel S. , Cen Steven Y. , Feng Qiushi , Rose Dorian R. , Behrman Andrea L. , Azen Stanley P. , Duncan Pamela W.
Published: January 2012

Background and Purpose—

Better understanding of fall risk poststroke is required for developing screening and prevention programs. This study characterizes falls in the Locomotor Experience Applied Post-Stroke (LEAPS) randomized clinical trial, describes the impact of 2 walking recovery interventions on falls, and examines the value of clinical assessments for predicting falls.

Methods—

Community-dwelling ambulatory stroke survivors enrolled in LEAPS were assessed 2 months poststroke. Falls were monitored until 12 months poststroke and participants were characterized as multiple or injurious (M/I); single, noninjurious; or nonfallers. Incidence and time to M/I falls were compared across interventions (home exercise and locomotor training initiated 2 months [early-LTP] or 6 months [late-LTP] poststroke). Predictive value of 2-month clinical assessments for falls outcome was assessed.

Results—

Among the 408 participants, 36.0% were M/I, 21.6% were single, noninjurious, and 42.4% were nonfallers. Most falls occurred at home in the first 3 months after assessment. Falls incidence was highest for those with severe walking impairment who received early-LTP (
P
=0.025). Berg Balance Scale score ≤42/56 was the single best predictor of M/I falls.

Conclusions—

As individuals with stroke improve in walking capacity, risk for M/I falls remains high. Individuals walking <0.4 m/s are at higher risk for M/I falls if they receive early-LTP training. Berg Balance Scale score at 2 months poststroke is useful for informing falls risk, but it cannot account for the multifactorial nature of the problem. Falls prevention in stroke will require multifactorial risk assessment and management provided concomitantly with exercise interventions to improve mobility.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00243919.
Tracks of a Non-Main Path Traveler
Authors: Hallenbeck John M.
Published: January 2012

After an unconventional beginning in stroke research, I veered off the main path repeatedly to view problems from a different perspective. In this lecture summary, I would like to return to several points along the byways that led to research with some continuity.
Regulating Nanotechnologies: Risk, Uncertainty and the Global Governance Gap
Authors: Falkner Robert , Jaspers Nico
Published: January 2012

Nanosciences and nanotechnologies are set to transform the global industrial landscape, but the debate on how to regulate environmental, health and safety risks is lagging behind technological innovation. Current regulatory efforts are primarily focused on the national and regional level, while the international dimensions of nanotechnology governance are still poorly understood and rarely feature on the international agenda. However, with the ongoing globalization of nanosciences and the rapid expansion of international trade in nanomaterials, demand for international coordination and harmonization of regulatory approaches is set to increase. Yet, uncertainty about nanotechnology risk poses a profound dilemma for regulators and policy-makers. Uncertainty both creates demand for and stands in the way of greater international cooperation and harmonization of regulatory approaches. This article reviews the emerging debate on nanotechnology risk and regulatory approaches, investigates the current state of international cooperation and outlines the critical contribution that a global governance approach can make to the safe development of nanotechnologies.
Agreement Weakening at PF: A Reply to Benmamoun and Lorimor
Authors: Ackema Peter , Neeleman Ad
Published: January 2012

Benmamoun and Lorimor (2006) dispute the claim made in Ackema and Neeleman 2003 that certain agreement alternations in Standard Arabic, and various related phenomena, can successfully be analyzed in terms of postsyntactic spell-out rules that are sensitive to prosodic structure. In this reply, we argue that the data discussed by Benmamoun and Lorimor do not warrant their conclusion, and in fact provide further evidence in favor of our original analysis.
Having ‘Need’ and Needing ‘Have’
Authors: Harves Stephanie , Kayne Richard S.
Published: January 2012

A survey of a number of the world’s languages reveals that only those languages that have a transitive verb used to express possession (i.e., Have-languages) also have a transitive verb ‘need’. No Be-language lacking a transitive verb for possession has a transitive verb ‘need’. This generalization suggests a Hale and Keyser ( 1993 , 2002 )–style incorporation approach, whereby nominal ‘need’ incorporates to an unpronounced verbal HAVE, yielding transitive verbal ‘need’.