bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental Influences on Caribbean Fish Catch
Authors: Jury Mark R.
Published: April 2011

A Caribbean fishery index is used to identify contrasting environmental conditions in atmosphere and ocean reanalysis fields associated with high- and low-catch years over the period 1971–2004. A number of composite features are noted: cooler surface temperatures and warmer, drier weather across the southern half of the Caribbean favors higher catch rates. There is a ridge of elevated sea level on 16°N. South of the ridge the Caribbean Current is strengthened while north of the ridge anomalous eastward currents flow past the Antilles Islands. The atmospheric Hadley circulation weakens in years of high catch and tropical cyclones are rare. This paper uncovers basin-scale forcing of aggregate fish catch, reflecting a north-south gradient in land-atmosphere hydrology, and composite oceanographic differences based on reanalysis data. In addition, seasonal and interannual cycles of ocean productivity are investigated using satellite ocean color. Summertime upwelling along the coast of Venezuela joins fresher waters from the North Brazil Current to infuse the Caribbean ecosystem with higher nutrients.
Management of Bladder Cancer following Solid Organ Transplantation
Authors: Tomaszewski Jeffrey J. , Larson Jeffrey A. , Smaldone Marc C. , Hayn Matthew H. , Jackman Stephen V.
Published: April 2011

Objective. Present our experience managing bladder cancer following liver and renal transplantation.Methods. Single institution retrospective review of patients diagnosed with bladder urothelial carcinoma (BUC) following solid organ transplantation between January 1992 and December 2007.Results. Of the 2,925 renal and 2,761 liver transplant recipients reviewed, we identified eleven patients (0.2%) following transplant diagnosed with BUC. Two patients with low grade T1 TCC were managed by TURBT. Three patients with CIS and one patient with T1 low grade BUC were treated by TURBT and adjuvant BCG. All four are alive and free of recurrence at a mean follow-up of 51 ± 22 months. One patient with T1 high grade BUC underwent radical cystectomy and remains disease free with a follow-up of 98 months. Muscle invasive TCC was diagnosed in four patients at a median of 3.6 years following transplantation. Two patients are recurrence free at 24 and 36 months following radical cystectomy. Urinary diversion and palliative XRT were performed in one patient with un-resectable disease.Conclusions. Bladder cancer is uncommon following renal and liver transplantation, but it can be managed successfully with local and/or extirpative therapy. The use of intravesical BCG is possible in select immunosuppressed patients.
Boundary Value Problems for q‐Difference Inclusions
Authors: Ahmad Bashir , Ntouyas Sotiris K.
Published: April 2011

We investigate the existence of solutions for a class of second‐order q‐difference inclusions with nonseparated boundary conditions. By using suitable fixed‐point theorems, we study the cases when the right‐hand side of the inclusions has convex as well as nonconvex values.
The Transcription Factor Evi-1 Is Overexpressed, Promotes Proliferation, and Is Prognostically Unfavorable in Infratentorial Ependymomas
Authors: Koos Björn , Bender Sebastian , Witt Hendrik , Mertsch Sonja , Felsberg Jörg , Beschorner Rudi , Korshunov Andrey , Riesmeier Barbara , Pfister Stefan , Paulus Werner , Hasselblatt Martin
Published: April 2011

Purpose: Ependymomas are glial tumors of presumably radial glial origin that share morphologic similarities with ependymal cells. The molecular genetics of ependymomas of supratentorial, infratentorial, and spinal location is heterogeneous. We aimed at identifying pathways operative in the development of infratentorial ependymomas.

Experimental Design: To do so, gene expression profiles of tumor cells laser microdissected from infratentorial ependymomas (n = 15) were compared with that of nonneoplastic ependymal cells laser microdissected from autopsy tissue (n = 7).

Results: Among 31 genes significantly overexpressed (>5-fold) in ependymomas, transcription factor EVI1 (ecotropic viral integration site 1) showed the highest overexpression (35-fold). Evi-1 protein expression could be confirmed in formalin-fixed, paraffin-embedded samples of 26 of 28 infratentorial ependymomas but only in 7 of 47 nonependymal glial tumors (P < 0.001). Furthermore, MDS1/EVI1 fusion transcripts were detectable in 17 of 28 infratentorial ependymomas and significantly correlated with MGMT (O6-methylguanine-DNA-methyltransferase) promoter hypermethylation (P < 0.05). In primary infratentorial ependymoma cells, transfection with EVI1-specific siRNAs resulted in significant growth inhibition [48 hours: 87% ± 2% and 74% ± 10% as compared with control (mean ± SD; P < 0.001)]. The prognostic role of EVI1 could further be validated in an independent cohort of 39 infratentorial and 26 supratentorial ependymomas on the basis of mRNA expression profiling. Although in supratentorial ependymomas EVI1 expression status had no prognostic impact, in infratentorial ependymomas, high EVI1 expression was associated with shorter overall survival and progression-free survival.

Conclusions: To conclude, the transcription factor Evi-1 is overexpressed in infratentorial ependymomas, promotes proliferation of ependymal tumor cells, and is prognostically unfavorable. Clin Cancer Res; 17(11); 3631–7. ©2011 AACR.
Relaxin Enhances the Collagenolytic Activity and In Vitro Invasiveness by Upregulating Matrix Metalloproteinases in Human Thyroid Carcinoma Cells
Authors: Bialek Joanna , Kunanuvat Usakorn , Hombach-Klonisch Sabine , Spens Antje , Stetefeld Joerg , Sunley Kevin , Lippert Dustin , Wilkins John A. , Hoang-Vu Cuong , Klonisch Thomas
Published: April 2011

In this study, we identified differential expression of immunoreactive matrix metalloproteinase 2 (MMP2)/gelatinase A, membrane-anchored MT1-MMP/MMP14, and human relaxin-2 (RLN2) in human benign and malignant thyroid tissues. MMP2 and MT1-MMP were detected in the majority of thyroid cancer tissues and colocalized with RLN2-positive cells. MMP2 was mostly absent in goiter tissues and, similar to RLN2, may serve as a marker for thyroid cancer. MMP2 and MT1-MMP were identified as novel RLN2 targets. RLN2 caused a significant downregulation of tissue inhibitor of MMP (TIMP) 3 protein levels but did not change the expression levels of MMP13, and TIMP1, TIMP2, and TIMP4 in human thyroid carcinoma cells. RLN2 failed to affect the expression of MMP1, 3, 8, and 9 in the thyroid carcinoma cells investigated. Stable RLN2 transfectants secreted enhanced levels of bioactive MMP2 which contributed to the increased collagenolytic activity and in vitro invasiveness into collagen matrix by human thyroid cancer cells. Three-dimensional reconstitution of confocal fluorescent microscopy images revealed larger-sized invadopodia, with intense MT1-MMP accumulation at the leading migrating edge in RLN2 transfectants when compared with enhanced green fluorescent protein clones. In RLN2 transfectants actin stress fibers contributed to pseudopodia formation. In conclusion, enhanced tumor cell invasion by RLN2 involves the formation of MT1-MMP–enriched invadopodia that lead to increased collagenolytic cell invasion by human thyroid cancer cells. Mol Cancer Res; 9(6); 673–87. ©2011 AACR.
Celecoxib Inhibits Interleukin-6/Interleukin-6 Receptor–Induced JAK2/STAT3 Phosphorylation in Human Hepatocellular Carcinoma Cells
Authors: Liu Yan , Liu Aiguo , Li Huameng , Li Chenglong , Lin Jiayuh
Published: April 2011

Growing evidence shows an association between chronic liver inflammation and hepatocellular carcinoma (HCC) development. STAT3, which is associated with inflammation and cellular transformation, is constitutively activated in human HCC tissues but not in normal human liver tissues. Although interleukin-6 (IL-6) is elevated in the serum of patients with HCC, it is not fully understood whether STAT3 constitutive activation is positively correlated with autocrine IL-6 secreted by HCC cells. Here, we reported that in HCC cells, the elevated levels of both IL-6 and IL-6 receptor (IL-6R, gp80), not IL-6 alone, correlated with STAT3 activation. We also explored whether the anticancer effects of celecoxib, an anti-inflammatory drug, may be due to the inhibition of the IL-6/STAT3 pathway in HCC cells. Our results showed that celecoxib decreased STAT3 phosphorylation by reducing Janus-activated kinase (JAK2) phosphorylation and caused apoptosis in HCC cells. Celecoxib could also block exogenous IL-6–induced STAT3 phosphorylation and nuclear translocation. Moreover, we observed more significant inhibition of cell viability when celecoxib was combined with doxorubicin or sorafenib. We conclude that the elevated levels of IL-6/IL-6R may be correlated with STAT3 activation in HCC cells. Celecoxib may be a candidate for HCC therapy through blocking IL-6/STAT3 pathway and can be combined with other anticancer drugs to reduce drug resistance caused by IL-6/STAT3 signals. Cancer Prev Res; 4(8); 1296–305. ©2011 AACR.
Onset and Recurrence of Depression as Predictors of Cardiovascular Prognosis in Depressed Acute Coronary Syndrome Patients: A Systematic Review
Authors: Zuidersma Marij , Thombs Brett D. , de Jonge Peter
Published: April 2011

Background: Depression after acute coronary syndrome (ACS) is associated with worse cardiac outcomes. This systematic review evaluated whether depressed ACS patients are at differential risk depending on the recurrence and timing of onset of depressive episodes. Methods: MEDLINE, EMBASE and PsycINFO were searched from inception to 11 April 2009. Additionally, reference lists and recent tables of contents of 34 selected journals were manually searched. Eligible studies evaluated cardiovascular outcomes for subgroups of ACS patients with depression or depressive symptoms according to recurrence or onset. Results: Six studies were included that reported outcomes for subgroups of ACS patients with first-ever versus recurrent depression. Four of these reported also outcomes for post-ACS onset versus pre-ACS onset depression, and incident versus nonincident depression. Worse outcomes (odds ratio >1.4) were reported for ACS patients with first-ever depression in 3 of 6 studies (1 study p < 0.05), for patients with post-ACS onset depression in 3 of 4 studies (1 study p < 0.05, but better outcomes in one study) and for patients with incident depression in 2 of 4 studies (no studies p < 0.05). Conclusions: Although it is still suggested that ACS patients with first and new-onset depression are at particularly increased risk of worse prognosis, the inconsistent results from the studies included in this systematic review show that there is no consistent evidence to support such statements.
Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain
Authors: Richardson R. Mark , Kells Adrian P. , Martin Alastair J. , Larson Paul S. , Starr Philip A. , Piferi Peter G. , Bates Geoffrey , Tansey Lisa , Rosenbluth Kathryn H. , Bringas John R. , Berger Mitchel S. , Bankiewicz Krystof S.
Published: April 2011

Background/Aims: A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods: Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results: The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions: This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion.
Distinguishing between Development and Change: Reviving Organismic-Developmental Theory
Authors: Raeff Catherine
Published: April 2011

The goal of this paper is to contribute to the revival of Heinz Werner’s organismic-developmental theory by considering some of its key claims in relation to contemporary developmental theory and research. The organismic-developmental definition of development in terms of differentiation and integration is first discussed in relation to contemporary systems theory. It is then synthesized with contemporary sociocultural theory, specifically the position that development occurs as individuals participate with others in cultural practices. Ultimately, it is argued that defining development in terms of differentiation and integration offers a systematic framework for distinguishing between change and development. Some implications of organismic-developmental theory for conducting research are discussed, and the paper ends with suggestions for future theorizing and research.
Anatomical Location of the Pedunculopontine Nucleus in the Human Brain: Diffusion Tensor Imaging Study
Authors: Yeo Sang Seok , Kim Seong Ho , Ahn Young Hwan , Son Su Min , Jang Sung Ho
Published: April 2011

We investigated the anatomical location of the pedunculopontine nucleus (PPN) in the human brain using diffusion tensor imaging. Forty normal healthy subjects were recruited. To confirm the boundary of the PPN, we analyzed the superior cerebellar peduncle and medial lemniscus using DTI-Studio software. We identified the PPN on red green blue (RGB) images, and defined four points of the PPN and four boundaries of the midbrain: point a – the most anterior point, point b – the most posterior point, point c – the most medial point, point d – the most lateral point; anterior boundary – the line of the most posterior point of the interpeduncular fossa, posterior boundary – the line of the upper part of the inferior colliculus, lateral boundary – the line of the most lateral point of the midbrain, medial boundary – the line of the midline of the midbrain. Points a and b were located at an average of 20.19 and 30.52% from the anterior boundary, respectively. By contrast, points c and d were located at an average of 22.50 and 41.65% from the medial boundary, respectively. We believe that the methodology and data of this study would be helpful in research and procedures on the PPN.
Nicotine-Induced Morphological Changes in Rat Aorta: The Protective Role of Melatonin
Authors: Rodella Luigi Fabrizio , Rossini Claudia , Favero Gaia , Foglio Eleonora , Loreto Carla , Rezzani Rita
Published: April 2011

We analyzed the morphological changes in rat aortas during nicotine administration in order to investigate the involvement of vascular smooth muscle cells (VSMCs) in the regulation of vascular wall homeostasis. We also considered the possibility of restoring VSMC changes using melatonin as an antioxidant. We studied 4 groups of animals over 56 days. Three groups of rats were used as controls (the first without treatment, the second with melatonin alone and the third with nicotine alone). The last group of rats was orally treated with nicotine for the first 28 days and with melatonin for the last 28 days. Morphological changes in vessels were evaluated by histological procedures and immunohistochemical analysis using thrombospondin-1 (TSP-1), transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor-1 (PAI-1) and CD31 antibodies. We demonstrated that TSP-1, TGF-β1 and PAI-1 increased after nicotine administration. We believe that TSP-1 is responsible for neointima formation and that it is able to influence TGF-β1 and PAI-1 expression. Histological and immunohistochemical analysis by CD31 antibody showed that only a few endothelial cells were present in the aorta after nicotine administration compared to controls and rats treated with melatonin after nicotine administration. Moreover, histological analysis showed that neointima formation was present after nicotine treatment. Furthermore, melatonin inhibited neointima formation increasing TSP-1 expression. The ability of melatonin to inhibit neointima formation suggests that it could be a useful treatment for homeostasis of vascular walls.
Proliferation, Apoptosis and Expression of Non-Collagenous Proteins: Differences between the Upper and the Lower Jaw Bone in vitro
Authors: Graf Hans-Ludwig , Brueckner Martin , Troeger Ursula , Hilbig Heidegard
Published: April 2011

One of the effects observed during several screening studies for osteocompatibility in vitro was that cells derived from the upper and lower jaw exhibited distinct differences regarding proliferation. Therefore, the aim of this study was to examine systematically whether a single osteoblast possesses abilities which are specific to the upper or lower jaw. Both human maxillary and mandibular bone samples without any clinical or radiographic evidence of pathology were obtained from 4 male donors aged between 40 and 45 years. Cells were cultured for up to 25 days to investigate in vitro development. Total and apoptotic cell numbers were estimated by image analysis. Cells were identified as bone-like cells using immunocytochemical determination of bone sialoprotein (BSP) and osteocalcin expression. The number of healthy cells was significantly higher for cells of the lower jaw compared to those of the upper jaw. The number of apoptotic cells showed an inverse pattern. The expression pattern of osseo-inductive BSP correlated with the proliferation rate of the cells. The pattern of osteocalcin expression was related to the number of apoptotic cells. Our findings are new but were anticipated regarding the well-known differences in the healing process around implants in the lower jaw versus the upper jaw. Additionally, a relationship between our results and some diseases of the lower/upper jaw seems obvious. Future work on cell responses to biomaterials should define the origin of the cells more precisely.
Geophagy in Brown Spider Monkeys (Ateles hybridus) in a Lowland Tropical Rainforest in Colombia
Authors: Link Andres , de Luna Ana Gabriela , Arango Ricardo , Diaz Maria Clara
Published: April 2011

Spider monkeys and howler monkeys are the only Neotropical primates that eat soil from mineral licks. Not all species within these genera visit mineral licks, and geophagy has been restricted to populations ofAteles belzebuth belzebuth,Ateles belzebuth chamekandAlouatta seniculusin western Amazonian rainforests. With the aid of a camera trap we studied the visitation patterns of a group of brown spider monkeys(Ateles hybridus)to a mineral lick at Serrania de Las Quinchas, in Colombia. Spider monkeys visited the lick frequently throughout the year, with a monthly average of 21.7 ± 7.2 visits per 100 days of camera trapping (n = 14 months). Spider monkeys visited the mineral lick almost always on days with no rain, or very little (<3 mm) rain, suggesting that proximate environmental variables might determine spider monkeys’ decisions to come to the ground at the licks. This study expands the geographical occurrence of mineral lick use by spider monkeys providing additional data for future assessments on the biogeographical correlates of mineral lick use by platyrrhines.
Astragalosides Reduce Cisplatin Ototoxicity in Guinea Pigs
Authors: Xiong Min , He Qinglian , Wang Jian , Lai Huangwen
Published: April 2011

Cisplatin is known to cause high-frequency neurosensory hearing loss. While reactive oxygen species have been shown to play a role, reactive nitrogen species have been implicated, but not proven to be involved, in cisplatin ototoxicity. The purpose of the present study was to investigate the role of nitric oxide (NO) in cisplatin ototoxicity by administering astragalosides, a natural antioxidant, in conjunction with cisplatin. Guinea pigs were injected with cisplatin, astragalosides or both. Auditory brainstem-evoked responses (ABRs) were measured before and 3 days after cisplatin administration. The cochlear tissue was then assayed for NO and malondialdehyde (MDA), and cochleae were also examined by scanning electron microscopy. Cisplatin alone caused significant ABR threshold shifts at all stimuli tested, whereas astragalosides alone caused no shifts. There was a significant reduction in threshold shift for clicks, 8-kHz and 16-kHz tone bursts (but not 32 kHz) when astragalosides was given with cisplatin. Both the MDA concentration and the NO concentration in the astragalosides/cisplatin group were significantly lower than those of the cisplatin group. Correspondingly, the loss of outer hair cells in the astragalosides/cisplatin group was much less than that in the cisplatin group. This suggests that astragalosides reduces cisplatin ototoxicity by its antioxidant property.
Dehydration with High Natriuretic Peptide Levels! A Word of Caution
Authors: Alzand B.S.N. , Mihl C. , Brunner La Rocca H.P.
Published: April 2011

B-type natriuretic peptide is secreted primarily by cardiomyocytes in response to increased ventricular or atrial wall stress reflecting volume or pressure overload. The relationship between natriuretic peptides and the severity of heart failure is well established. We present here a case where natriuretic peptide levels were increased due to dehydration in the abscence of renal impairment. Normalization of natriuretic peptide level was achieved by stopping the diuretics and the administration of normal saline.
Interaction between Adiponectin and Aldosterone
Authors: Flynn Colleen , Bakris George L.
Published: April 2011

More than two thirds of the US population are considered overweight or obese. Adipocytes are now appreciated as important endocrine organs, secreting various factors with hormonal effects. Several different adipokines have been identified, including adiponectin, which is associated with improved insulin sensitivity, a better lipoprotein profile, and lower rates of vascular inflammation and cardiovascular disease. Several studies have identified the renin-angiotensin-aldosterone system as important in the regulation of adiponectin. These studies lay the fundamental groundwork for developing targeted therapies with potential to reduce the burden of obesity-associated diseases, such as the cardiorenal metabolic syndrome.
Changes in Cognitive Function over 3 Years after First-Ever Stroke and Predictors of Cognitive Impairment and Long-Term Cognitive Stability: The Erlangen Stroke Project
Authors: Liman T.G. , Heuschmann P.U. , Endres M. , Flöel A. , Schwab S. , Kolominsky-Rabas P.L.
Published: April 2011

Background and Purpose: Cognitive impairment (CI) is frequent after stroke, but data from population-based stroke cohorts on the natural course of CI are limited. The purpose of this study was to determine changes in cognitive status over 3 years after stroke. Methods: Data were collected from the Erlangen Stroke Project, an ongoing population-based stroke registry. The Mini-Mental State Examination (MMSE) for assessing global cognitive function was used; CI was defined as an MMSE score <24. Results: From February 1998 to January 2006, 630 patients with first-ever stroke were included. Prevalence rates of CI at 3 months, 1 and 3 years were 15, 13, and 12%. In multivariable analysis, stroke severity, i.e. Barthel index (p < 0.001), age (OR = 1.03; 95% CI = 1.00–1.05) and diabetes mellitus (OR = 2.03; 95% CI = 1.13–3.67) were associated with CI at 3 months. Recovery rate from CI at 3 months after stroke was found to be 31% over the following 3 years. Intact cognitive function rate was 71% over 3 years and inversely associated with age (OR = 0.96; 95% CI = 0.96–0.94) and stroke severity (p < 0.001). Conclusion: CI is frequent among stroke survivors and associated with age, stroke severity, and diabetes mellitus, but recovery occurs in approximately one third of the patients over the course of 3 years. Factors affecting intact cognitive function over time are increasing age and stroke severity.
Role of Complement Cascade in Abdominal Aortic Aneurysms
Authors: Hinterseher Irene , Erdman Robert , Donoso Larry A. , Vrabec Tamara R. , Schworer Charles M. , Lillvis John H. , Boddy Amy M. , Derr Kimberly , Golden Alicia , Bowen William D. , Gatalica Zoran , Tapinos Nikos , Elmore James R. , Franklin David P. , Gray John L. , Garvin Robert P. , Gerhard Glenn S. , Carey David J. , Tromp Gerard , Kuivaniemi Helena
Published: April 2011

Objective—

The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs).

Methods and Results—

Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls.
In silico
analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for signal transducer and activator of transcription (STAT)5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues.

Conclusion—

These results provide strong evidence that the complement cascade plays a role in human AAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression.
TGF-β
1
-Mediated Fibrosis and Ion Channel Remodeling Are Key Mechanisms in Producing the Sinus Node Dysfunction Associated With
SCN5A
Deficiency and Aging
Authors: Hao Xiaojin , Zhang Yanmin , Zhang Xinzhao , Nirmalan Mahesh , Davies Laura , Konstantinou Dimitrios , Yin Fei , Dobrzynski Halina , Wang Xin , Grace Andrew , Zhang Henggui , Boyett Mark , Huang Christopher L.-H. , Lei Ming
Published: April 2011

Background—

Mutations in the cardiac Na
+
channel gene (
SCN5A
) can adversely affect electric function in the heart, but effects can be age dependent. We explored the interacting effects of
Scn5a
disruption and aging on the pathogenesis of sinus node dysfunction in a heterozygous
Scn5a
knockout (
Scn5a
+/−
) mouse model.

Methods and Results—

We compared functional, histological, and molecular features in young (3 to 4 month) and old (1 year) wild type and
Scn5a
+/−
mice. Both
Scn5a
disruption and aging were associated with decreased heart rate variability, reduced sinoatrial node automaticity, and slowed sinoatrial conduction. They also led to increased collagen and fibroblast levels and upregulated transforming growth factor-β
1
(TGF-β
1
) and vimentin transcripts, providing measures of fibrosis and reduced Nav1.5 expression. All these effects were most noticeable in old
Scn5a
+/−
mice. Na
+
channel inhibition by Nav1.5-E3 antibody directly increased TGF-β
1
production in both cultured human cardiac myocytes and fibroblasts. Finally, aging was associated with downregulation of a wide range of ion channel and related transcripts and, again, was greatest in old
Scn5a
+/−
mice. The quantitative results from these studies permitted computer simulations that successfully replicated the observed sinoatrial node phenotypes shown by the different experimental groups.

Conclusions—

These results implicate a tissue degeneration triggered by Nav1.5 deficiency manifesting as a TGF-β
1
-mediated fibrosis accompanied by electric remodeling in the sinus node dysfunction associated with
Scn5a
disruption or aging. The latter effects interact to produce the most severe phenotype in old
Scn5a
+/−
mice. In demonstrating this, our findings suggest a novel regulatory role for Nav1.5 in cellular biological processes in addition to its electrophysiologic function.
Coffee Consumption and Incidence of Heart Failure in Women
Authors: Levitan Emily B. , Ahmed Hanna N. , Mittleman Murray A. , Wolk Alicja
Published: April 2011

Background—

Previous studies of the relationship between coffee consumption and incidence of heart failure (HF) have not been consistent, with both potential benefit and potential harm reported. We therefore examined the association between coffee consumption and HF hospitalization or mortality in women.

Methods and Results—

We conducted a prospective, observational study of 34 551 participants of the Swedish Mammography Cohort who were 48 to 83 years old and did not have HF, diabetes, or myocardial infarction at baseline. Diet was measured using food-frequency questionnaires. Cox models were used to calculate hazard ratios of HF hospitalization or death from HF as the primary cause, as determined through the Swedish inpatient and cause-of-death registers between January 1, 1998, and December 31, 2006. Over 9 years of follow-up, 602 HF events occurred. Women who consumed ≥5 cups of coffee per day did not have higher rates of HF events than those who consumed <5 cups per day (multivariable-adjusted hazard ratio, 0.93; 95% confidence interval, 0.72 to 1.20). Compared with women who consumed ≤1 cup of coffee per day, hazard ratios were 1.01, 0.82, 0.94, and 0.87 for women who consumed 2, 3, 4, and ≥5 cups per day, respectively (
P
for trend=0.23). Further adjustment for self-reported hypertension did not change the results.

Conclusions—

In this population of middle-aged and older women, we did not find an association between coffee consumption and incidence of HF events.
A Method to Measure Myocardial Calcium Handling in Adult Drosophila
Authors: Lin Na , Badie Nima , Yu Lin , Abraham Dennis , Cheng Heping , Bursac Nenad , Rockman Howard A. , Wolf Matthew J.
Published: April 2011

Rationale:

Normal cardiac physiology requires highly regulated cytosolic Ca
2+
concentrations and abnormalities in Ca
2+
handling are associated with heart failure. The majority of approaches to identifying the components that regulate intracellular Ca
2+
dynamics rely on cells in culture, mouse models, and human samples. However, a genetically robust system for unbiased screens of mutations that affect Ca
2+
handling remains a challenge.

Objective:

We sought to develop a new method to measure myocardial Ca
2+
cycling in adult
Drosophila
and determine whether cardiomyopathic fly hearts recapitulate aspects of diseased mammalian myocardium.

Methods and Results:

Using engineered transgenic
Drosophila
that have cardiac-specific expression of Ca
2+
-sensing fluorescent protein, GCaMP2, we developed methods to measure parameters associated with myocardial Ca
2+
handling. The following key observations were identified: (1) Control

w
1118

Drosophila
hearts have readily measureable Ca
2+
-dependent fluorescent signals that are dependent on L-type Ca
2+
channels and SR Ca
2+
stores and originate from rostral and caudal pacemakers. (2) A fly mutant,

held-up
2

(

hdp
2

), that has a point mutation in troponin I and has a dilated cardiomyopathic phenotype demonstrates abnormalities in myocardial Ca
2+
handling that include increases in the duration of the 50% rise in intensity to peak intensity, the half-time of fluorescence decline from peak, the full duration at half-maximal intensity, and decreases in the linear slope of decay from 80% to 20% intensity decay. (3) Hearts from

hdp
2

mutants had reductions in caffeine-induced Ca
2+
increases and reductions in ryanodine receptor (RyR) without changes in L-type Ca
2+
channel transcripts in comparison with

w
1118

.

Conclusions:

Our results show that the cardiac-specific expression of GCaMP2 provides a means of characterizing propagating Ca
2+
transients in adult fly hearts. Moreover, the adult fruit fly heart recapitulates several aspects of Ca
2+
regulation observed in mammalian myocardium. A mutation in
Drosophila
that causes an enlarged cardiac chamber and impaired contractile function is associated with abnormalities in the cytosolic Ca
2+
transient as well as changes in transcript levels of proteins associated with Ca
2+
handling. This new methodology has the potential to permit an examination of evolutionarily conserved myocardial Ca
2+
-handing mechanisms by applying the vast resources available in the fly genomics community to conduct genetic screens to identify new genes involved in generated Ca
2+
transients and arrhythmias.
Metabotropic Regulation of RhoA/Rho-Associated Kinase by L-type Ca
2+
Channels
Authors: Fernández-Tenorio Miguel , Porras-González Cristina , Castellano Antonio , del Valle-Rodríguez Alberto , López-Barneo José , Ureña Juan
Published: April 2011

Background:

Sustained vascular smooth muscle contraction is mediated by extracellular Ca
2+
influx through L-type voltage-gated Ca
2+
channels (VGCC) and RhoA/Rho-associated kinase (ROCK)-dependent Ca
2+
sensitization of the contractile machinery. VGCC activation can also trigger an ion-independent metabotropic pathway that involves G-protein/phospholipase C activation, inositol 1,4,5-trisphosphate synthesis, and Ca
2+
release from the sarcoplasmic reticulum (calcium channel-induced Ca
2+
release). We have studied the functional role of calcium channel-induced Ca
2+
release and the inter-relations between Ca
2+
channel and RhoA/ROCK activation.

Methods and Results:

We have used normal and genetically modified animals to study single myocyte electrophysiology and fluorimetry as well as cytosolic Ca
2+
and diameter in intact arteries. These analyses were complemented with measurement of tension and RhoA activity in normal and reversibly permeabilized arterial rings. We have found that, unexpectedly, L-type Ca
2+
channel activation and subsequent metabotropic Ca
2+
release from sarcoplasmic reticulum participate in depolarization-evoked RhoA/ROCK activity and sustained arterial contraction. We show that these phenomena do not depend on the change in the membrane potential itself, or the mere release of Ca
2+
from the sarcoplasmic reticulum, but they require the simultaneous activation of VGCC and the downstream metabotropic pathway with concomitant Ca
2+
release. During protracted depolarizations, refilling of the stores by a residual extracellular Ca
2+
influx through VGCC helps maintaining RhoA activity and sustained arterial contraction.

Conclusions:

These findings reveal that calcium channel-induced Ca
2+
release has a major role in tonic vascular smooth muscle contractility because it links membrane depolarization and Ca
2+
channel activation with metabotropic Ca
2+
release and sensitization (RhoA/ROCK stimulation).
MRI Using Ferumoxytol Improves the Visualization of Central Nervous System Vascular Malformations
Authors: Dósa Edit , Tuladhar Suchita , Muldoon Leslie L. , Hamilton Bronwyn E. , Rooney William D. , Neuwelt Edward A.
Published: April 2011

Background and Purpose—

Central nervous system vascular malformations (VMs) result from abnormal vasculo- and/or angiogenesis. Cavernomas and arteriovenous malformations are also sites of active inflammation. The aim of this study was to determine whether MRI detection of VMs can be improved by administration of ferumoxytol iron oxide nanoparticle, which acts as a blood pool agent at early time points and an inflammatory marker when taken up by tissue macrophages.

Methods—

Nineteen patients (11 men, 8 women; mean age, 47.5 years) with central nervous system VMs underwent 3-T MRI both with gadoteridol and ferumoxytol. The ferumoxytol-induced signal changes on the T1-, T2-, and susceptibility-weighted images were analyzed at 25 minutes (range, 21 to 30 minutes) and 24 hours (range, 22 to 27 hours).

Results—

Thirty-five lesions (capillary telangiectasia, n=6; cavernoma, n=21; developmental venous anomaly, n=7; arteriovenous malformation, n=1) were seen on the pre- and postgadoteridol images. The postferumoxytol susceptibility-weighted sequences revealed 5 additional VMs (3 capillary telangiectasias, 2 cavernomas) and demonstrated further tributary veins in all patients with developmental venous anomalies. The 24-hour T1 and T2 ferumoxytol-related signal abnormalities were inconsistent among patients and within VM types. No additional area of T1 or T2 enhancement was noted with ferumoxytol compared with gadoteridol in any lesion.

Conclusions—

Our findings indicate that the blood pool agent ferumoxytol provides important information about the number and true extent of VMs on the susceptibility-weighted MRI. The use of ferumoxytol as a macrophage imaging agent in the visualization of inflammatory cells within and around the lesions warrants further investigation.
Improving Stroke Risk Stratification Using the CHADS
2
and CHA
2
DS
2
-VASc Risk Scores in Patients With Paroxysmal Atrial Fibrillation by Continuous Arrhythmia Burden Monitoring
Authors: Boriani Giuseppe , Botto Giovanni Luca , Padeletti Luigi , Santini Massimo , Capucci Alessandro , Gulizia Michele , Ricci Renato , Biffi Mauro , De Santo Tiziana , Corbucci Giorgio , Lip Gregory Y.H. ,   for the Italian AT-500 Registry Investigators
Published: April 2011

Background and Purpose—

In patients with atrial fibrillation (AF), stroke risk stratification schema do not consider AF parameters. The aim of the study is to assess the impact of combining risk factors with continuous AF burden monitoring.

Methods—

In this retrospective study 568 patients implanted with a DDDR-P pacemaker (AT-500; Medtronic) and a history of AF were continuously monitored for 1 year.

Results—

During follow-up, 14 patients (2.5%) had a thromboembolic event. Patients were divided into 3 groups: AF burden ≤5 minutes per day (AF-free; n=223 [39%]), AF burden >5 minutes but <24 hours per day (AF-5 minutes; n=179 [32%]), and AF burden ≥24 hours (AF-24 hours; n=166 [29%]). Patients were also classified according to CHADS
2
and CHA
2
DS
2
-VASc risk scores. The discrimination ability of each risk score was evaluated performing a logistic regression analysis and calculating the corresponding C-statistic. The addition of AF burden improved C-statistics: for CHADS
2
from 0.653 (
P
=0.051) to 0.713 (
P
=0.007); for CHA
2
DS
2
-VASc, from 0.898 (
P
<0.0001) to 0.910 (
P
<0.0001).

Conclusions—

The CHA
2
DS
2
-VASc score had a high sensitivity to predict thromboembolism. Implementation of device data on AF presence/duration/burden has the potential to contribute to improved clinical risk stratification and should be tested prospectively.
Safety and Outcomes of Intravenous Thrombolysis in Stroke Mimics
Authors: Tsivgoulis Georgios , Alexandrov Andrei V. , Chang Jason , Sharma Vijay K. , Hoover Steven L. , Lao Annabelle Y. , Liu Wei , Stamboulis Elefterios , Alexandrov Anne W. , Malkoff Marc D. , Frey James L.
Published: April 2011

Background and Purpose—

Efforts to increase the availability and shorten the time delivery of intravenous thrombolysis in patients with acute ischemic stroke carry the potential for tissue plasminogen activator administration in patients with diseases other than stroke, that is, stroke mimics (SMs). We aimed to determine safety and to describe outcomes of intravenous thrombolysis in SM.

Methods—

We retrospectively analyzed stroke registry data of consecutive acute ischemic stroke admissions treated with intravenous thrombolysis over a 6-year-period. The admission National Institutes of Health Stroke Scale score, vascular risk factors, ischemic lesions on brain MRI (routinely performed as part of diagnostic work-up), and discharge modified Rankin Scale scores were documented. Initial stroke diagnosis in the emergency department was compared with final discharge diagnosis. SM diagnosis was based on the absence of ischemic lesions on diffusion-weighted imaging sequences in addition to an alternate discharge diagnosis. Symptomatic intracranial hemorrhage was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by National Institutes of Health Stroke Scale score increase of ≥4 points.

Results—

Intravenous thrombolysis was administered in 539 patients with acute ischemic stroke (55% men; mean age, 66±15 years). Misdiagnosis of acute ischemic stroke was documented in 56 cases (10.4%; 95% CI, 7.9% to 13.3%). Conversion disorder (26.8%), complicated migraine (19.6%), and seizures (19.6%) were the 3 most common final diagnoses in SM. SMs were younger (mean age, 56±13 years) and had milder baseline stroke severity (median National Institutes of Health Stroke Scale, 6; interquartile range, 4) compared with patients with confirmed acute ischemic stroke (mean age, 67±14 years; median National Institutes of Health Stroke Scale, 8; interquartile range, 10;
P
<0.001). There was no case of symptomatic intracranial hemorrhage in SMs (0%; 95% CI, 0% to 5.5%); 96% of SMs were functionally independent at hospital discharge (modified Rankin Scale, 0 to 1).

Conclusions—

Our single-center data indicate favorable safety and outcomes of intravenous thrombolysis administered to SM.
How Sample Paths of Leaky Integrate-and-Fire Models Are Influenced by the Presence of a Firing Threshold
Authors: Giraudo Maria Teresa , Greenwood Priscilla E. , Sacerdote Laura
Published: April 2011

Neural membrane potential data are necessarily conditional on observation being prior to a firing time. In a stochastic leaky integrate-and-fire model, this corresponds to conditioning the process on not crossing a boundary. In the literature, simulation and estimation have almost always been done using unconditioned processes. In this letter, we determine the stochastic differential equations of a diffusion process conditioned to stay below a level S up to a fixed time t1 and of a diffusion process conditioned to cross the boundary for the first time at t1. This allows simulation of sample paths and identification of the corresponding mean process. Differences between the mean of free and conditioned processes are illustrated, as well as the role of noise in increasing these differences.
A Finite-Sample, Distribution-Free, Probabilistic Lower Bound on Mutual Information
Authors: VanderKraats Nathan D. , Banerjee Arunava
Published: April 2011

For any memoryless communication channel with a binary-valued input and a one-dimensional real-valued output, we introduce a probabilistic lower bound on the mutual information given empirical observations on the channel. The bound is built on the Dvoretzky-Kiefer-Wolfowitz inequality and is distribution free. A quadratic time algorithm is described for computing the bound and its corresponding class-conditional distribution functions. We compare our approach to existing techniques and show the superiority of our bound to a method inspired by Fano’s inequality where the continuous random variable is discretized.
Steinernema vulcanicum n. sp. (Rhabditida: Steinernematidae), a new entomopathogenic nematode species from Sicily (Italy)
Authors: Tarasco Eustachio , Clausi Mirella , Rappazzo Giancarlo , Vinciguerra Maria Teresa , Longo Agata
Published: April 2011

A new species of entomopathogenic nematode, Steinernema vulcanicum n. sp., is described from the slopes of Mount Etna (Sicily, Italy). It was recovered from soil in a chestnut wood. Molecular and morphological data indicate that the new species belongs to the glaseri group of Steinernema spp. The new species can be distinguished from the other described species of the group by morphological characteristics, crossbreeding tests and by the DNA sequences of ITS1 rDNA, 12S and cox1 mitochondrial loci. Steinernema vulcanicum n. sp. is characterised by the long and slender male spicules, with manubrium wider than long, velum prominent, rounded tip with ventral concavity and tail without mucro. The female has double epiptygmata in both generations. The third-stage infective juveniles have an average body length of 1200 μm, excretory pore generally located level with posterior part of the pharyngeal corpus (D% = 47-68), lateral field pattern of variable formula and hyaline part of tail forming ca 50% of its length. The DNA sequences, life cycle and the endosymbiotic bacterium of S. vulcanicum n. sp., Xenorhabdus kozodoii, indicate the similarity of the new species with S. arenarium, S. apuliae and S. boemarei, from which it can be distinguished by both morphological and molecular characters.
Drawing Our Fish in the Sand: Secret Biblical Allusions in the Music of U2
Authors: Galbraith Deane
Published: April 2011

Confronted with a popular music subculture which is predominantly antipathetic to Christianity, the charismatic-evangelical members of rock band U2 double code their lyrics in such a manner that Christian references are hidden from mainstream listeners and media while being readily recognizable to their Christian fans. The device of allusion is especially amenable to this end, as the meaning of an allusion can only be considered by a reader or listener who possesses the requisite competency in respect of the evoked text(s). Through their utilization of biblical allusions, U2 therefore construct two different, perhaps even irreconcilable, groups of listeners—a knowledgeable Christian in-group and an unknowledgeable non-Christian out-group. With detailed reference to U2's songs, this paper examines the covert tendencies of allusion and the manner by which it is able to engage the listener's intertextual imagination. The paper also distinguishes a secret or hidden allusion from a generic allusion on pragmatic and socio-cultural grounds, and demonstrates the potential of secret allusions to increase semantic indeterminacy. Lastly, the paper examines some examples of the reception of the U2 song 'Magnificent' which demonstrate the effectiveness of U2's secret biblical allusions in creating two largely discrete groups of listeners.
Africa in Retrospect: Russia, Iran and Chinese Arms Supplies to Sudan
Authors: McFarland Sherri
Published: April 2011

This study provides requisite information on the thorny civil war and destructive situation in the Republic of Sudan, which has led to the indictment of the sitting Sudanese Head of State in 2009. This paper will provide an in depth discussion regarding increased weapons transfers and its adverse impact on the conflict in Sudan. Additionally, theoretical frameworks regarding the foreign policies of nation-states, power, and resource conflict will be utilized to analyze the Sudanese government’s relationships with China, Russia and Iran as well as its relationship with the marginalized communities of the Sudan such as Darfur and the Nuba Mountains. Information has been provided to underscore the major players in the conflict, whereby Russia, Iran and China are considered culprits in the arms race in the area. Russia, China and Iran have continued to supply arms to Sudan despite the institution of a UN arms embargo in 2004. Although the weapons procurement chain in Sudan demands a comprehensive analysis of both state and non-state actors a close examination of its relationship with various nation-states such as China, Iran and Russia will provide a greater understanding of the economic and political environment that has contributed to the increase of weapons transfers which has adversely impacted internal and regional security.
On the Conversation Between Theologians and Economists: A Contribution to Public Theology
Authors: Peil Jan , Wijngaards Aloys , van den Hoogen Toine
Published: April 2011

This article seeks to contribute to the development of a conversation between public theology and economics. A major problem for this conversation is the dichotomy between normative and positive judgements about our social reality. This translates into the use of distinctive concepts of value rationality and instrumental rationality. This article proposes an alternative conception of rationality that offers a way out of the positive‐normative dichotomy and embeds our approach in the framework of public theology.