bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating behavior-based indices of connectivity into spatially explicit population models
Authors: Rizkalla C.E. , Swihart R.K.
Published: February 2012

Measuring connectivity in fragmented landscapes remains a central problem in ecology. Connectivity metrics range from descriptors of landscape structure to direct observations of a species’ ability to move to and colonize a forest patch. We constructed individual-based spatially explicit population models for a guild of forest rodents in Indiana to test the ability of structural and actual, or behavioral, measures of connectivity to predict patch and landscape occupancy and abundance. Model accuracy was assessed using comparisons with data from trapping studies. Predicted abundances within patches correlated with empirical data for five out of six species, but predicted patterns of patch occupancy corresponded with observations for only one species. Discrepancies may be due to inaccurate parameter values or the absence from the models of ecological processes such as conspecific attraction and competition. Nonetheless, the models demonstrated the utility of patch immigration as a measure of connectivity in explaining population abundance in fragmented landscapes. We discuss potential methods of collecting these behavior-based data.
Proportional underwater call type usage by Weddell seals (Leptonychotes weddellii) in breeding and nonbreeding situations
Authors: Doiron Elyse E. , Rouget Philippe A. , Terhune John M.
Published: February 2012

Proportional underwater call type usage by Weddell seals ( Leptonychotes weddellii (Lesson, 1826)) near Mawson, Antarctica, investigated the hypothesis that certain call types function specifically in breeding behaviour. Recordings were collected at various sites in 2000 and 2002 from June to December. Twenty-four hour recordings were collected in 2002 at two sites. One hundred consecutive calls from each of 248 recordings were classified into one of ten common call types. Time to 100 calls provided the calling rate. The study period was divided into four periods representing initial sea-ice formation, pre-pupping, pupping, and mating. Calling rate and light–dark differences were also examined. No presence–absence differences were observed for any of the call types with season. The largest difference between nonbreeding and breeding situations was an increase from 32.2% to 38.1% for descending whistles (F[3,244] = 4.483, p = 0.004). Trills gradually increased from 1.8% to 7.3% toward the mating period (F[3,244] = 30.932, p < 0.001). The proportion of trills, chugs, descending whistles, and other call types also varied with calling rate and light–dark conditions. Some pre-reproductive behaviours may occur in winter, but no call types of Weddell seals function solely in the breeding season.
Incubation patterns of a shorebird with rapid multiple clutches, the Mountain Plover (Charadrius montanus)
Authors: Skrade P.D.B. , Dinsmore S.J.
Published: February 2012

The rapid multiclutch parental care system of the Mountain Plover ( Charadrius montanus J.K. Townsend, 1837) presents a rare opportunity to examine sex-specific differences in avian uniparental care. We monitored incubation activity for this species using a combination of video (857 h at 25 nests during 2007) and temperature data-recording (>10 000 h at 124 nests during 2006–2008) at breeding areas in Montana. We modeled possible differences in nocturnal activity using the duration of off-bouts of incubating adults and included the effects of nest age, day of season, ambient temperature, precipitation, and time of departure. Males, on average, made 1.48 departures·h–1over a 24 h period (SE = 0.35 departures·h–1, n = 6 days) and females made 1.41 departures·h–1(SE = 0.11 departures·h–1, n = 26 days). The mean duration of nocturnal off-bouts for males was 0.38 h (SE = 0.01 h, n = 1925), while the mean duration of female off-bouts was 0.36 h (SE = 0.01 h, n = 2716). Plovers had longer off-bouts from their nests in the middle of the night and early in the breeding season. This study furthers an understanding of incubation patterns in an uncommon avian parental care system and provides important behavioral information about a species of conservation concern.
EFFECTS OF TISSUE GROWTH ON ROBUST FORMATION OF MORPHOGEN GRADIENT
Authors: YIN HONGWEI , WEN XIAOQING , ZHOU TIANSHOU
Published: February 2012

Morphogens, such as Decapentaplegic (Dpp) in Drosophila wing disc, are locally produced and spread to other regions in organs, forming gradients that control the interrelated pattern and growth of developing organs. During development, morphogen gradients must be robust to changes in intracellular and extracellular environments so as to provide target genes precise information to determine cell fates and the resulting spatial pattern on the proper position and at the proper time. However, how tissue growth affects the robust formation of morphogen gradient remains to be fully explored. Here, we model, using a reaction–advection–diffusion equation, a morphogen transport mechanism including tissue growth. By introducing and analyzing a robustness index that measures the effect of tissue growth on the formation of the morphogen gradient, we demonstrate that tissue growth can enlarge the range of morphogen gradient. In particular, tissue growth in the region near the source can efficiently filter the shift resulting from the changes in the production rate in each of steady-state and pre-steady-state situations, but the efficiency depends on growth rate and spatial position in either situation as well as on the time of development in the pre-steady-state situation. These results indicate that tissue growth is an nonnegligible factor for the robust formation of morphogen gradient.
LATERAL CASIMIR FORCE BETWEEN DEEPLY CORRUGATED DIELECTRIC AND METALLIC PLATES
Authors: AZARI ARASH , MIRI MIRFAEZ
Published: February 2012

We study the lateral Casimir force between corrugated dielectric plates. We use the dielectric contrast perturbation theory [R. Golestanian, Phys. Rev. Lett.95, 230601, (2005)], which allows us to consider arbitrary deformations with large amplitudes. We consider sinusoidal, rectangular, and sawtooth corrugations, for samples made of silicon and gold. We use the plasma and Drude–Lorentz models for the permittivity of gold and silicon, respectively. For these geometries and materials, the lateral Casimir force is not a sinusoidal function of the relative lateral displacement of plates when the gap between the plates in comparable with the depth of the corrugations. Our results facilitate the design of miniaturized devices based on lateral Casimir forces.
BIOPHYSICAL APPLICATIONS OF SCANNING ION CONDUCTANCE MICROSCOPY (SICM)
Authors: ANARIBA FRANKLIN , ANH JOON HYUNG , JUNG GOO-EUN , CHO NAM-JOON , CHO SANG-JOON
Published: February 2012

Scanning probe microscopy (SPM) techniques represent one of the most promising approaches to probe the physical and chemical properties of nanoscale materials. The growing convergence of physics and biology has demanded nanotechnology tools to understand the fundamental physics of biological systems. Despite the advantages of SPM techniques, there have been challenges with its application to characterization of biological specimens. In recent times, the development of one class of SPM technique, scanning ion conductance microscopy (SICM), has overcome these limitations and enabled noninvasive, nanoscale investigation of live cells. In this review article, we present the theory behind the SICM operating principles and data modeling. Based on this framework, we discuss recent research advances where the SICM technique has proven technically superior. SICM applications discussed herein include imaging of cell topography, monitoring of live cell dynamics, mechanical stimulation of live cells, and surface patterning. Additional findings on the combination of SICM with other SPM techniques as well as patch clamp electrophysiology are presented in the context of building integrated knowledge on the structure and function of live cells. In summary, SICM bridges physics and biology to enable a range of important biomedical applications.
DEFORMED GAS OF p, q-BOSONS: VIRIAL EXPANSION AND VIRIAL COEFFICIENTS
Authors: GAVRILIK A. M. , REBESH A. P.
Published: February 2012

In the study of many-particle systems both the interaction of particles can be essential and such feature as their internal (composite) structure. To describe these aspects, the theory of deformed oscillators is very efficient. Viewing the particles as p, q-deformed bosons, in the corresponding p, q-Bose gas model we obtain in explicit form virial expansion along with the 2nd to 5th virial coefficients. The obtained virial coefficients depend on the deformation parameters p, q in the form symmetric under p ↔ q, and at p → 1, q → 1 turn into those known for usual bosons. Besides real parameters, we analyze the case of complex mutually conjugate p and q and find interesting implications. Also, the critical temperature is derived (for the p, q-Bose gas) and compared with the Tc of standard case of bosons condensation. Similar results are presented for the deformed Bose gas model of the Tamm–Dancoff (TD) type.
BOOLEAN DELAY EQUATIONS ON NETWORKS IN ECONOMICS AND THE GEOSCIENCES
Authors: COLUZZI BARBARA , GHIL MICHAEL , HALLEGATTE STÉPHANE , WEISBUCH GÉRARD
Published: February 2012

We study damage propagation in networks, with an emphasis on production-chain models. The models are formulated as systems of Boolean delay equations. This formalism helps take into account the complexity of the interactions between firms; it turns out to be well adapted to investigating propagation of an initial damage due to a climatic or other natural disaster.

We consider in detail the effects of distinct delays and forcing, which represent external intervention to prevent economic collapse. We also account for the possible presence of randomness in the links and the delays. The paper concentrates on two different network structures, periodic and random, respectively; their study allows one to understand the effects of multiple, concurrent production paths, and the role played by the network topology in damage propagation. Applications to the recent network modeling of climate variability are discussed.
CLIMATE MODE COVARIABILITY AND CLIMATE SHIFTS
Authors: TSONIS ANASTASIOS A. , SWANSON KYLE L.
Published: February 2012

It has previously been shown from the collective behavior of a network of observed climate indices that this network synchronized several times in the period 1900–2000. Further, it has been found that in those cases where the synchronous state was followed by a steady increase in the coupling strength between the indices, the synchronous state was destroyed, after which a new climate state emerged. These shifts are associated with significant changes in global temperature trend and in El Niño/Southern Oscillation variability. Subsequently, the evidence for such type of behavior has been found to occur in three climate simulations using state-of-the-art models as well as in the observed data in the 21st century. This was the first time that this mechanism, which appears consistent with the theory of synchronized chaos, has been discovered in a physical system of the size and complexity of the climate system. Here we extend this approach to consider proxy data for climate modes going back several centuries. While noise in the proxy data in some cases masks the mechanism, we find significant coherence between both synchronization and coupling and global temperature. These results provide further support that the above mechanism for climate shifts is a robust feature of the climate system.
STATISTICAL STUDY OF BIVALVE HIGH FREQUENCY MICROCLOSING BEHAVIOR: SCALING PROPERTIES AND SHOT NOISE ANALYSIS
Authors: SCHMITT FRANÇOIS G. , DE ROSA MARIE , DURRIEU GILLES , SOW MOHAMEDOU , CIRET PIERRE , TRAN DAMIEN , MASSABUAU JEAN-CHARLES
Published: February 2012

We consider bivalve (oyster) behavior using high frequency valvometry data. These data are obtained in the field in the Arcachon bay, with light-weight electrodes of millimeters size, attached to the molluscs, and linked by flexible wires to an electronic control unit which measures valve activity. The latter are able to move freely and open their valve with an amplitude which is linked to environmental and physiological conditions, in order to filter surrounding waters. We consider here daily data recorded every 0.1 sec for 16 different animals, corresponding to a total of 1 728 000 data points. Valvometry data show important intermittent activity at high frequency, with frequent and sudden "microclosing" events (meaning partial closures), at apparently random times and with random amplitudes. The overall frequency spectrum of valve opening time series show power-law behavior with a slope β = 1.6 ± 0.1. The random succession of closing events with random amplitudes suggests to consider a shot-noise analysis, with two independent stochastic processes representing respectively the times of these discrete shot noise events and their amplitudes. This shows that methods and approaches devoted to extreme values, chaotic dynamics, recurrence time statistics in geosciences and climate studies can also be used to study living organisms and their interactions with complex environments such as their local ecosystem.
SENSITIVITY ANALYSIS OF NONLINEAR MODELS TO PARAMETER PERTURBATIONS FOR SMALL SIZE ENSEMBLES OF MODEL OUTPUTS
Authors: IVANOV L. M. , TOKMAKIAN R. T.
Published: February 2012

A new technique for nonlinear sensitivity analysis of geophysical models for small size ensembles of model outputs has been developed. Such an analysis utilizes the following metrics: (a) Sobol–Saltelli sensitivity indices and cumulative distribution functions if perturbations of model parameters are random, and (b) a Hartley-like measure if perturbations of model parameters are nonrandom and parametrized through fuzzy sets. The indices and the Hartley-like measure allow for ranging model parameters along their significance to the model output. Our calculations demonstrate that accurate estimates of the sensitivity indices are possible even if an ensemble of random perturbations contains considerably less than 100 members. Some calculations were successfully provided for random ensembles with 20–30 members only but, in general 50–100 member ensembles are required to get robust and significant estimations of model sensitivity. The fuzzy set concept allows for robust estimations for small size nonrandom ensembles of model outputs (50–100 members) and accounts for additional a priori information on model sensitivity coming from different sources. The Lorenz 63 model (a few degrees of freedom) and the ocean component (POP) of the Community Climate System Model (CCSM3) (several thousand degrees of freedom) are used to illustrate the sensitivity analysis based on this approach.
NON-CONDENSING POLYMERIC GENE DELIVERY SYSTEMS: PRINCIPLES AND APPLICATIONS
Authors: JAIN SHARDOOL , ATTARWALA HUSAIN , AMIJI MANSOOR
Published: February 2012

Gene therapy holds tremendous promise in prevention and treatment of diseases as the approach is based on regulating the expression of genes that are responsible for pathological conditions. The biggest bottleneck for gene delivery has been the development of safe and efficacious delivery systems. Although non-viral vectors are considered as much safer options than their viral counterparts, they suffer from low transfection efficiency. In this review, we highlight the role of non-condensing polymeric delivery systems for oral and systemic gene delivery. Using evidence from contemporary literature, non-condensing polymeric microparticle and nanoparticle systems afford physical encapsulation of the nucleic acid construct and can be engineered for targeted delivery to tissues and cells. Additionally, these systems have shown less toxicity and afford sustained cytoplasmic DNA delivery for efficient nuclear uptake and transfection for both DNA vaccines and therapeutic genes.
GOLD NANOROD PHOTOTHERMAL THERAPY IN A GENETICALLY ENGINEERED MOUSE MODEL OF SOFT TISSUE SARCOMA
Authors: LIN KEVIN Y. , BAGLEY ALEXANDER F. , ZHANG ALEXIA Y. , KARL DANIEL L. , YOON SAM S. , BHATIA SANGEETA N.
Published: February 2012

Plasmonic nanomaterials are poised to impact the clinical management of cancer through their ability to convert externally applied energy into localized heat at sites of diseased tissue. However, characterization of plasmonic nanomaterials as cancer therapeutics has been limited to xenograft models, creating a need to extend these findings to more clinically relevant models of cancer. Here, we evaluate the method of photothermal ablation therapy in a genetically engineered mouse model (GEMM) of sarcoma, which more accurately recapitulates the human disease in terms of structure and biology than subcutaneous xenograft models. Using polyethylene glycol (PEG)-coated gold nanorods (PEG-NRs), we quantitatively evaluate the ability of nanoparticles to penetrate and accumulate in sarcomas through passive targeting mechanisms. We demonstrate that PEG-NR–mediated photothermal heating results in significant delays in tumor growth with no progression in some instances. Lastly, by evaluating our photothermal ablation protocol in a GEMM, we observe off-target heating effects that are not detectable in xenograft models and which may be of future clinical interest.
The endocannabinoid N-arachidonoyl dopamine (NADA) selectively induces oxidative stress-mediated cell death in hepatic stellate cells but not in hepatocytes
Authors: Wojtalla Alexandra , Herweck Frank , Granzow Michaela , Klein Sabine , Trebicka Jonel , Huss Sebastian , Lerner Raissa , Lutz Beat , Schildberg Frank Alexander , Knolle Percy Alexander , Sauerbruch Tilman , Singer Manfred Vincenz , Zimmer Andreas , Siegmund Sören Volker
Published: February 2012

The endocannabinoid system is a crucial regulator of hepatic fibrogenesis. We have previously shown that the endocannabinoid anandamide (AEA) is a lipid mediator that blocks proliferation and induces death in hepatic stellate cells (HSCs), the main fibrogenic cell type in the liver, but not in hepatocytes. However, the effects of other endocannabinoids such as N-arachidonoyl dopamine (NADA) have not yet been investigated. The NADA-synthesizing enzyme tyrosine hydroxylase was mainly expressed in sympathetic neurons in portal tracts. Its expression pattern stayed unchanged in normal or fibrotic liver. NADA dose dependently induced cell death in culture-activated primary murine or human HSCs after 2–4 h, starting from 5 μM. Despite caspase 3 cleavage, NADA-mediated cell death showed typical features of necrosis, including ATP depletion. Although the cannabinoid receptors CB1, CB2, or transient receptor potential cation channel subfamily V, member 1 were expressed in HSCs, their pharmacological or genetic blockade failed to inhibit NADA-mediated death, indicating a cannabinoid-receptor-independent mechanism. Interestingly, membrane cholesterol depletion with methyl-β-cyclodextrin inhibited AEA- but not NADA-induced death. NADA significantly induced reactive oxygen species formation in HSCs. The antioxidant glutathione (GSH) significantly decreased NADA-induced cell death. Similar to AEA, primary hepatocytes were highly resistant against NADA-induced death. Resistance to NADA in hepatocytes was due to high levels of GSH, since GSH depletion significantly increased NADA-induced death. Moreover, high expression of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH) in hepatocytes also conferred resistance towards NADA-induced death, since pharmacological or genetic FAAH inhibition significantly augmented hepatocyte death. Thus the selective induction of cell death in HSCs proposes NADA as a novel antifibrogenic mediator.
Preproendothelin-1 expression is negatively regulated by IFNγ during hepatic stellate cell activation
Authors: Li Tianxia , Shi Zengdun , Rockey Don C.
Published: February 2012

Endothelin-1 (ET-1), a powerful vasoconstrictor peptide, is produced by activated hepatic stellate cells (HSC) and promotes cell proliferation, fibrogenesis, and contraction, the latter of which has been thought to be mechanistically linked to portal hypertension in cirrhosis. Interferon-γ (IFNγ), a Th1 cytokine produced by T cells, inhibits stellate cell proliferation, fibrogenesis, and muscle-specific gene expression. Whether IFNγ-induced inhibitory effects are linked to regulation of ET-1 expression in activated stellate cells remains unknown. Here we examined IFNγ's effects on preproET-1 mRNA expression and the signaling pathways underlying this process. We demonstrated that preproET-1 mRNA expression in HSCs was prominently increased during cell culture-induced activation; IFNγ significantly inhibited both preproET-1 mRNA expression and ET-1 peptide production. Similar results were found in an in vivo model of liver injury and intraperitoneal administration of IFNγ. PreproET-1 promoter analysis revealed that IFNγ-induced inhibition of preproET-1 mRNA expression was closely linked to the AP-1 and Smad3 signaling pathways. Furthermore, IFNγ reduced JNK phosphorylation, which tightly was associated with decreased phosphorylation of downstream factors c-Jun and Smad3 and decreased binding activity of c-Jun and Smad3 in the preprpET-1 promoter. Importantly, IFNγ reduced both c-Jun mRNA and protein levels. Given the important role of ET-1 in wound healing, our results suggest a novel negative signaling network by which IFNγ inhibits preproET-1 expression, highlighting one potential molecular mechanism for IFNγ-induced host immunomodulation of liver fibrogenesis.
Platelets orchestrate remote tissue damage after mesenteric ischemia-reperfusion
Authors: Lapchak Peter H. , Kannan Lakshmi , Ioannou Antonis , Rani Poonam , Karian Peter , Dalle Lucca Jurandir J. , Tsokos George C.
Published: February 2012

Ischemia-reperfusion (I/R) injury is a leading cause of morbidity and mortality. A functional role for platelets in tissue damage after mesenteric I/R is largely unknown. The hypothesis that mesenteric I/R local and remote injury are platelet dependent was tested. Using a murine mesenteric I/R model, we demonstrate that platelets orchestrate remote lung tissue damage that follows mesenteric I/R injury and also contribute, albeit to a lesser degree, to local villi damage. While lung damage is delayed compared with villi damage, it increased over time and was characterized by accumulation of platelets in the pulmonary vasculature early, followed by alveolar capillaries and extravasation into the pulmonary space. Both villi and lung tissues displayed complement deposition. We demonstrate that villi and lung damage are reduced in mice made platelet deficient before I/R injury and that platelet transfusion into previously platelet-depleted mice before I/R increased both villi and lung tissue damage. Increased C3 deposition accompanied platelet sequestration in the lung, which was mostly absent in platelet-depleted mice. In contrast, C3 deposition was only minimally reduced on villi of platelet-depleted mice. Our findings position platelets alongside complement as a significant early upstream component that orchestrates remote lung tissue damage after mesenteric I/R and strongly suggest that reperfusion injury mitigating modalities should consider the contribution of platelets.
TNF-α induces upregulation of EGFR expression and signaling in human colonic myofibroblasts
Authors: Yoo James , Perez Citlali Ekaterina Rodriguez , Nie Wenxian , Edwards Robert A. , Sinnett-Smith James , Rozengurt Enrique
Published: February 2012

The myofibroblast has recently been identified as an important mediator of tumor necrosis factor-α (TNF-α)-associated colitis and cancer, but the mechanism(s) involved remains incompletely understood. Recent evidence suggests that TNF-α is a central regulator of multiple inflammatory signaling cascades. One important target of TNF-α may be the signaling pathway downstream of the epidermal growth factor receptor (EGFR), which has been associated with many human cancers. Here, we show that long-term exposure of 18Co cells, a model of human colonic myofibroblasts, with TNF-α led to a striking increase in cell surface EGFR expression, an effect that was completely inhibited by cycloheximide. Subsequent EGFR binding by EGF and heparin binding (HB)-EGF was associated with enhanced EGFR tyrosine kinase activity, prolonged ERK activation, and a significant increase in cyclooxygenase-2 (COX-2) expression compared with 18Co cells treated with EGF and HB-EGF alone. TNF-α also increased EGFR expression and signaling in primary myofibroblasts isolated from human colon tissue. TNF-α-induced upregulation of EGFR may be a plausible mechanism to explain the exaggerated cellular responsiveness that characterizes inflammatory bowel disease and that may contribute to a microenvironment that predisposes to colitis-associated cancer through enhanced COX-2 expression.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults
Authors: Raue Ulrika , Trappe Todd A. , Estrem Shawn T. , Qian Hui-Rong , Helvering Leah M. , Smith Rosamund C. , Trappe Scott
Published: February 2012

This investigation examined the effects of acute resistance exercise (RE), progressive resistance training (PRT), and age on the human skeletal muscle Transcriptome. Two cohorts of young and old adults [ study A: 24 yr, 84 yr ( n = 28); study B: 25 yr, 78 yr ( n = 36)] were studied. Vastus lateralis biopsies were obtained pre- and 4 h post-RE in conjunction with the 1st and 36th (last) training session as part of a 12-wk PRT program in study A, whereas biopsies were obtained in the basal untrained state in study B. Additionally, the muscle fiber type specific (MHC I and MHC IIa) Transcriptome response to RE was examined in a subset of young and old women from study A. Transcriptome profiling was performed using HG U133 Plus 2.0 Arrays. The main findings were 1) there were 661 genes affected by RE during the 1st and 36th training bout that correlated with gains in muscle size and strength with PRT (termed the Transcriptome signature of resistance exercise adaptations); 2) the RE gene response was most pronounced in fast-twitch (MHC IIa) muscle fibers and provided additional insight into the skeletal muscle biology affected by RE; 3) skeletal muscle of young adults is more responsive to RE at the gene level compared with old adults and age also affected basal level skeletal muscle gene expression. These skeletal muscle Transcriptome findings provide further insight into the molecular basis of sarcopenia and the impact of resistance exercise at the mixed muscle and fiber type specific level.
Phospho-specific Flow: Fixating on the Target
Authors: Levis Mark
Published: February 2012

Targeted therapies are all the rage in oncology research these days. The problem remains as to how to confirm that the target is actually being hit in vivo. This report describes the application of phospho-specific flow cytometry to establish in vivo target inhibition in real time. Clin Cancer Res; 18(6); 1493–5. ©2012 AACR.
Notes from the Field: “Green” Chemoprevention as Frugal Medicine
Authors: Fahey Jed W. , Talalay Paul , Kensler Thomas W.
Published: February 2012

Prevention trials of whole foods or simple extracts offer prospects for reducing an expanding global burden of cancer effectively, and in contrast to promising isolated phytochemicals or pharmaceuticals, frugally. We use the term “green” chemoprevention to differentiate a food-centered approach that is sustainable in underserved populations. It can be applied to personalized medicine just as well as a pharmaceutical approach, but only green chemoprevention can be applied in both rich and poor settings. This MiniReview discusses some of the challenges of conducting food-based trials in developing countries, with particular emphasis on moving the limited number of promising phase II trials forward as placebo-controlled randomized trials, the gold standard for prevention studies. How does one define a placebo for a food? What is the regulatory context of such a food-based product? How can such products be produced and standardized to the benefit of a larger, individual trial, and importantly, the research community at large? What are the challenges and opportunities of conducting such trials in the international setting? Finally, how does one make the science practical? Cancer Prev Res; 5(2); 179–88. ©2012 AACR.
Effect of Terbutaline on Latency Period in Preterm Premature Rupture of Membranes
Authors: Kulmala Lalita , Phupong Vorapong
Published: February 2012

Aims: To assess whether terbutaline is able to prolong the latency period in women with preterm premature rupture of membranes (PPROM) and compare maternal and neonatal morbidity and mortality in the terbutaline and nontocolysis groups. Methods: This study retrospectively analyzed data from women with singleton pregnancies (gestational ages between 28 and 34 weeks) suffering from PPROM from January 1998 to December 2009. Results: A total of 163 cases of PPROM were analyzed; there were 61 cases (37.4%) in the terbutaline group and 102 cases (62.6%) in the nontocolysis group. The median latency period was comparable in the two groups (78 vs. 75 h, p = 0.44). The percentage of patients who did not deliver within 48 h was significantly higher in the terbutaline group compared with the nontocolysis group (78.7 vs. 62.7%, p = 0.03). There were no differences in maternal morbidity and mortality, and neonatal mortality between the two groups. Interestingly, neonatal infectious morbidity was significantly higher in the terbutaline group when compared with the nontocolysis group. Conclusions: Terbutaline cannot prolong the latency period in PPROM. There were no differences in maternal morbidity and mortality. However, neonatal infectious morbidity was higher in the terbutaline group.
Copy Number Variations on Chromosome 4q26–27 Are Associated with Cantu Syndrome
Authors: Kurban Mazen , Kim Chong Ae , Kiuru Maija , Fantauzzo Katherine , Cabral Rita , Abbas Ossama , Levy Brynn , Christiano Angela M.
Published: February 2012

Background: Cantu syndrome is a rare condition which is characterized clinically by hypertrichosis, cardiomegaly and bone abnormalities. Inherited hypertrichoses are very rare human disorders whose incidence has been estimated as low as 1 in 1 billion. The genetic basis of hypertrichosis is largely unknown, and currently no single gene has been directly implicated in its pathogenesis, although position effects have been reported. Methods: We analyzed the DNA of a patient with Cantu syndrome on the Affymetrix Cytogenetics Whole-Genome 2.7M array for copy number variations (CNVs). We then performed genomic copy number quantification using qPCR, and finally we performed gene expression analysis in the hair follicle for the genes lying within and around the region of the duplication. Results: We identified a 375 kb duplication on chromosome 4q26–27. The duplication region encompassed three genes, which included MYOZ2, USP53 and FABP2. MYOZ2 and USP53 are known to be highly expressed in the cardiac muscle, and we found that USP53 is expressed in the hair follicle. Conclusion: We propose that CNVs involving chromosome 4q26–27 may be associated with Cantu syndrome. CNVs spanning several genes may help define the molecular basis of syndromes which have unrelated clinical features.
Efficacy and Safety of Limbal-Conjunctival Autografting with Limbal Fixation Sutures after Pterygium Excision
Authors: Han Sang Beom , Hyon Joon Young , Hwang Jeong-Min , Wee Won Ryang
Published: February 2012

Purpose: To evaluate the efficacy and safety of limbal-conjunctival autografting with limbal fixation sutures after pterygium excision. Methods: We retrospectively reviewed the records of 90 patients (103 eyes) who received limbal-conjunctival autografts with limbal fixation sutures after excision of the primary pterygium (82 eyes) and recurrent pterygium (21 eyes). Results: The study subjects comprised 41 male patients (47 eyes) and 49 female patients (56 eyes) with a mean age of 51.1 ± 10.5 years (range 32–77). The mean follow-up period was 18.9 ± 9.2 months (range 12–50). Among the 103 eyes, recurrence occurred in 2 eyes (1.9%) after 2 and 4 months, respectively. As complications, 1 case of conjunctival cyst and 2 cases of pseudopterygium at the donor site were reported. Conclusions: Limbal-conjunctival autografting with limbal fixation sutures appears to be an effective and safe method of reducing the recurrence rate after pterygium excision.
Incidence and Subtypes of MCI and Dementia 1 Year after First-Ever Stroke in Patients without Pre-Existing Cognitive Impairment
Authors: Ihle-Hansen Hege , Thommessen Bente , Bruun Wyller Torgeir , Engedal Knut , Øksengård Anne Rita , Stenset Vidar , Løken Kirsti , Aaberg Morten , Fure Brynjar
Published: February 2012

Background: Post-stroke dementia is defined as any dementia occurring after stroke, and includes vascular, degenerative and mixed dementia. The aim of this study was to assess the incidence of dementia and mild cognitive impairment (MCI) one year after stroke in a population free from pre-stroke cognitive decline, and to investigate the different aetiological subtypes of post-stroke dementia and MCI, using a novel method of subclassification in order to separate vascular causes of MCI or dementia from a neurodegenerative disease. Methods: All patients with a first-ever stroke and TIA admitted to the stroke unit of Asker and Bærum Hospital were invited. After 12 months, dementia and MCI were diagnosed. Sub-classification was made using MRI findings, the results of biomarkers in cerebrospinal fluid and the patients’ clinical cognitive profile. Results: 36 (19.6%) patients developed dementia during the first year after stroke and 69 (37.5%) developed MCI. Fourteen (13.3%) were diagnosed as suffering from degenerative cognitive disease, 34 (32.4%) from vascular cognitive disease, and 57 (54.3%) from mixed disease. Conclusion: Fifty-seven percent suffered from cognitive impairment one year after stroke and only one third from isolated vascular cognitive disease. Post-stroke cognitive impairment is complex with a high coexistence of vascular and degenerative changes.
Protective Effects of Edaravone on Experimental Spinal Cord Injury in Rats
Authors: Özgiray Erkin , Serarslan Yurdal , Öztürk Oktay Hasan , Altaş Murat , Aras Mustafa , Söğüt Sadık , Yurtseven Taşkın , Oran İsmail , Zileli Mehmet
Published: February 2012

Background: Spinal cord injury (SCI) is a leading cause of morbidity and mortality among youth and adults. Secondary injury mechanisms within the spinal cord (SC) are well known to cause deterioration after an acute impact. Free radical scavengers are among the most studied agents in animal models of SCI. Edaravone is a scavenger of hydroxyl radicals. Methods: We aimed to measure and compare the effects of both methylprednisolone and edaravone on tissue and on serum concentrations of nitric oxide (NO), malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and tissue total antioxidant capacity (TAC) in rats with SCI. SCI was induced in four groups of Wistar albino rats by a weight-drop method. The neurological function of the rats was periodically tested. At the end of the experiment, blood samples were collected, and SC tissue samples were harvested for biochemical evaluation. Results: The tissue level of NO was decreased in the edaravone-treated group compared with the no-treatment group (p < 0.05). The tissue levels of SOD and GSH-Px were higher in the edaravone-treated group than in the no-treatment group (p < 0.05). The serum levels of NO were lower in the edaravone-treated and methylprednisolone-treated groups than in the no-treatment group (p < 0.05). The serum levels of SOD in the edaravone-treated group did not differ from those of any other group. The serum levels of MDA in the edaravone-treated and no-treatment groups were higher than in the two other groups (p < 0.05). Tissue levels of MDA in the edaravone-treated group were lower than in the no-treatment group (p < 0.05). Tissue levels of TAC in the edaravone-treated group were higher than in the no-treatment and methylprednisolone-treated groups (p < 0.05). The neurological outcome scores of the animals in treatment groups did not depict any statistically significant improvement in motor functions. However, edaravone seemed to prevent further worsening of the immediate post-SCI neurological status. Conclusion: Our biochemical analyses indicate that edaravone is capable of blunting the increased oxidative stress that follows SCI. We show, for the first time, that edaravone enhances the TAC in SC tissue. This beneficial effect of edaravone on antioxidant status may act to minimize the secondary neurological damage that occurs during the acute phase after SCI.
Retroclival Epidural Hematoma in a Child Affected by Whiplash Cervical Injury: A Typical Case of a Rare Condition
Authors: Becco de Souza Rodrigo , Brasileiro de Aguiar Guilherme , Sette dos Santos Marcelo Eduardo , Acioly Marcus André
Published: February 2012

Traumatic posterior fossa epidural hematomas are uncommon lesions. Among these lesions, retroclival epidural hematomas (REDH) are particularly rare conditions that usually occur in the pediatric population due to predisposing anatomical features in this patient group. We describe a typical case of traumatic REDH from the mechanism of trauma to outcome. This 8-year-old girl was involved in a motor vehicle accident leading to whiplash cervical injury and cranial nerve palsy. Any children involved in a severe motor vehicle accident with such a sequence of events should raise suspicion for prompt diagnosis.
A Phase II Study of Capecitabine plus Oxaliplatin as First-Line Chemotherapy in Elderly Patients with Advanced Gastric Cancer
Authors: Xiang Xiao Jun , Zhang Ling , Qiu Feng , Yu Feng , Zhan Zheng Yu , Feng Miao , Yan Jun , Zhao Jian Guo , Xiong Jian Ping
Published: February 2012

Objective: This study aimed at assessing the efficacy and safety of oxaliplatin plus oral capecitabine (XELOX regimen) as first-line chemotherapy in elderly patients with advanced gastric cancer (AGC). Patients and Methods: Forty-six eligible patients aged ≧70 years with previously untreated AGC received oxaliplatin 130 mg/m2 intravenously over a 2-hour period on day 1 plus oral capecitabine 850 mg/m2 twice daily on days 1–14, every 3 weeks. Results: All patients were evaluable for toxicity and 45 patients for efficacy. A median of 6 cycles (range 1–8) was administered. The overall response rate was 48.9% (95% CI 34–64) with 1 complete response, 21 partial responses, 15 stable diseases and 8 progressions. Median time to progression was 6.0 months (95% CI 3.9–8.1), and the median overall survival was 10.0 months (95% CI 8.6–11.4). Toxicity was fairly mild. Grade 3 toxicities included neutropenia (6.5%), thrombocytopenia (2.2%), nausea (2.2%), vomiting (4.3%), diarrhea (4.3%) as well as peripheral neuropathy (2.2%); grade 4 toxicities occurred in none of the patients. Conclusion: The XELOX regimen with capecitabine at a lower dose of 850 mg/m2 is active, fairly tolerable and conveniently delivered as first-line chemotherapy for elderly AGC patients.
Familial Aggregation of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia with Solid Tumors and Myeloid Malignancies
Authors: Kristinsson Sigurdur Y. , Goldin Lynn R. , Turesson Ingemar , Björkholm Magnus , Landgren Ola
Published: February 2012

Lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) is a B-cell disorder resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphoplasmacytic cells. LPL/WM is a very rare disease, with an incidence rate of 3–4 cases per million people per year.Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors in the pathogenesis of LPL/WM. In addition, data show that genetic factors are of importance in the etiology of LPL/WM. In this paper, we will review the current knowledge about familiality of LPL/WM and provide novel data on solid tumors and myeloid malignancies in first-degree relatives of LPL/WM patients.
Survival in a Large Elderly Population of Patients with Dementia and Other Forms of Psychogeriatric Diseases
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn
Published: February 2012

Background: Dementia and other psychogeriatric diseases in elderly patients bring an increased risk of death. Better knowledge of prognosis in elderly patients affected by dementia or mental illness should be of great importance in order to improve care plans and assist in medical decisions. Methods: We have investigated the survival time in 2,112 patients with dementia and other forms of psychogeriatric diseases, enrolled during 1990 to 2005 and followed up until 2009, and the influence of diagnoses, plasma homocysteine level, presence of vascular disease and renal impairment. Results: The survival time after diagnosis in most diagnostic groups is about a third compared to an average population of similar age and sex. Age was the main predictor of survival time in all patients. Conclusions: All diagnoses, except in patients with subjective cognitive impairments, showed an increased mortality. These estimates can be used for prognosis and planning for patients, carers, service providers and policy makers.
Cognitive and Graded Activity Training Can Alleviate Persistent Fatigue After Stroke
Authors: Zedlitz Aglaia M.E.E. , Rietveld Toni C.M. , Geurts Alexander C. , Fasotti Luciano
Published: February 2012

Background and Purpose—

Fatigue is a common, persistent consequence of stroke, and no evidence-based treatments are currently available to alleviate fatigue. A new treatment combining cognitive therapy (CO) with graded activity training (GRAT), called COGRAT, was developed to alleviate fatigue and fatigue-related symptoms. This study compared the effectiveness of the COGRAT intervention with a CO-only intervention after a 3-month qualification period without intervention.

Methods—

This randomized, controlled, assessor-blind clinical trial was conducted in 8 rehabilitation centers. Eighty-three stroke patients (>4 months after stroke) were randomly assigned to 12 weeks of CO or COGRAT after qualification. Seventy-three patients completed treatment and 68 were available at follow-up. Primary outcomes (Checklist Individual Strength–subscale Fatigue (CIS-f); self-observation list–fatigue (SOL-f)) and secondary outcomes (Hospital Anxiety and Depression Scale, Stroke-Adapted Sickness Impact Profile, SOL-pain, SOL-sleep-D, 6-minute walk test) were collected at baseline (before and after qualification period) and after treatment (immediate and 6-month follow-up).

Results—

The qualification period showed stable outcome measures. Both treatments showed significant beneficial effects on fatigue (CIS-f: η
p
2
=0.48,
P
<0.001) and other outcomes (except pain and anxiety) with intention-to-treat analyses. Gains for the COGRAT group exceeded those in the CO group on number of individuals showing clinical improvement on the CIS-f (≥8 points: 58% versus 24%) and on physical endurance (η
p
2
=0.20,
P
<0.001).

Conclusions—

A 12-week cognitive therapy program can alleviate persistent fatigue after stroke. The best results are obtained when cognitive therapy is augmented with graded activity training.

Clinical Trial Registration—

URL:
http://www.trialregister.nl
. Unique identifier: NTR2704.
Standardizing the Structure of Stroke Clinical and Epidemiologic Research Data
Authors: Saver Jeffrey L. , Warach Steven , Janis Scott , Odenkirchen Joanne , Becker Kyra , Benavente Oscar , Broderick Joseph , Dromerick Alexander W. , Duncan Pamela , Elkind Mitchell S.V. , Johnston Karen , Kidwell Chelsea S. , Meschia James F. , Schwamm Lee ,   for the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Common Data Element Working Group
Published: February 2012

Background and Purpose—

The National Institute of Neurological Disorders and Stroke initiated development of stroke-specific Common Data Elements (CDEs) as part of a project to develop data standards for funded clinical research in all fields of neuroscience. Standardizing data elements in translational, clinical, and population research in cerebrovascular disease could decrease study start-up time, facilitate data sharing, and promote well-informed clinical practice guidelines.

Methods—

A working group of diverse experts in cerebrovascular clinical trials, epidemiology, and biostatistics met regularly to develop a set of stroke CDEs, selecting among, refining, and adding to existing, field-tested data elements from national registries and funded trials and studies. Candidate elements were revised on the basis of comments from leading national and international neurovascular research organizations and the public.

Results—

The first iteration of the National Institute of Neurological Disorders and Stroke (NINDS) stroke-specific CDEs comprises 980 data elements spanning 9 content areas: (1) biospecimens and biomarkers; (2) hospital course and acute therapies; (3) imaging; (4) laboratory tests and vital signs; (5) long-term therapies; (6) medical history and prior health status; (7) outcomes and end points; (8) stroke presentation; and (9) stroke types and subtypes. A CDE website provides uniform names and structures for each element, a data dictionary, and template case report forms, using the CDEs.

Conclusions—

Stroke-specific CDEs are now available as standardized, scientifically vetted, variable structures to facilitate data collection and data sharing in cerebrovascular patient-oriented research. The CDEs are an evolving resource that will be iteratively improved based on investigator use, new technologies, and emerging concepts and research findings.
Role of Central Nervous System Periostin in Cerebral Ischemia
Authors: Shimamura Munehisa , Taniyama Yoshiaki , Katsuragi Naruto , Koibuchi Nobutaka , Kyutoku Mariko , Sato Naoyuki , Allahtavakoli Mohammad , Wakayama Kouji , Nakagami Hironori , Morishita Ryuichi
Published: February 2012

Background and Purpose—

Although periostin, an extracellular matrix glycoprotein, plays pivotal roles in survival, migration, and regeneration in various cells, its expression and function in the brain are still unknown. Here, we investigated the expression and role of periostin in the ischemic brain.

Methods—

Expression of full-length periostin (periostin 1 [Pn1]) and its splicing variant lacking exon 17 (periostin 2 [Pn2]) was examined by real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining in male C57BL6/J mice. The actions of periostin were examined in adult primary neuronal culture and in a transient middle cerebral artery occlusion (tMCAo) model.

Results—

Expression of Pn2, but not of Pn1, mRNA was markedly changed after tMCAo. Pn2 mRNA was decreased in the ischemic core at 3 hours after ischemia. At 24 hours, Pn2 mRNA was significantly increased in both the peri-ischemic and ischemic regions. Periostin was mainly observed in neurons in normal brain. However, neuronal expression of periostin was decreased temporarily in the ischemic region, but increased in astrocytes and around endothelial cells at 24 hours after tMCAo. Of importance, intracerebroventricular injection of Pn2 resulted in a significant reduction in infarct volume at 24 hours after tMCAo associated with phosphorylation of Akt. Also, the Pn2-treated mice survived longer until 1 week after tMCAo. Pn2 significantly inhibited neuronal death under hypoxia and stimulated neurite outgrowth.

Conclusions—

Here, we demonstrated that periostin was expressed in the brain, and exogenous Pn2 exhibited neuroprotective effects and accelerated neurite outgrowth. Additional studies on periostin may provide new insights into the treatment of ischemic stroke.