bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative stress enhances IL-8 and inhibits CCL20 production from intestinal epithelial cells in response to bacterial flagellin
Authors: Ivison Sabine M. , Wang Ce , Himmel Megan E. , Sheridan Jared , Delano Jonathan , Mayer Matt L. , Yao Yu , Kifayet Arnawaz , Steiner Theodore S.
Published: July 2010

Intestinal epithelial cells act as innate immune sentinels, as the first cells that encounter diarrheal pathogens. They use pattern recognition molecules such as the Toll-like receptors (TLRs) to identify molecular signals found on microbes but not host cells or food components. TLRs cannot generally distinguish the molecular signals on pathogenic bacteria from those found in commensals, yet under healthy conditions epithelial immune responses are kept in check. We hypothesized that, in the setting of tissue damage or stress, intestinal epithelial cells would upregulate their responses to TLR ligands to reflect the greater need for immediate protection against pathogens. We treated Caco-2 cells with the TLR5 agonist flagellin in the presence or absence of H2O2and measured chemokine production and intracellular signaling pathways. H2O2increased flagellin-induced IL-8 (CXCL8) production in a dose-dependent manner. This was associated with synergistic phosphorylation of p38 MAP kinase and with prolonged I-κB degradation and NF-κB activation. The H2O2-mediated potentiation of IL-8 production required the activity of p38, tyrosine kinases, phospholipase Cγ, and intracellular calcium, but not protein kinase C or protein kinase D. H2O2prolonged and augmented NF-κB activation by flagellin. In contrast to IL-8, CCL20 (MIP3α) production by flagellin was reduced by H2O2, and this effect was not calcium dependent. Oxidative stress biases intestinal epithelial responses to flagellin, leading to increased production of IL-8 and decreased production of CCL20. This suggests that epithelial cells are capable of sensing the extracellular environment and adjusting their antimicrobial responses accordingly.
Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities
Authors: Kohli Rohit , Kirby Michelle , Setchell Kenneth D. R. , Jha Pinky , Klustaitis Kori , Woollett Laura A. , Pfluger Paul T. , Balistreri William F. , Tso Patrick , Jandacek Ronald J. , Woods Stephen C. , Heubi James E. , Tschoep Matthias H. , D'Alessio David A. , Shroyer Noah F. , Seeley Randy J.
Published: July 2010

Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome. Changes in intestinal and hepatic physiology after ileal interposition (transposition) surgery (IIS) are not well understood. Our aim was to elucidate the adaptation of the interposed ileum, which we hypothesized, would lead to early bile acid reabsorption in the interposed ileum, thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments. Rats with diet-induced obesity were randomized to IIS, with 10 cm of ileum repositioned distal to the duodenum, or sham surgery. A subgroup of sham rats was pair-fed to IIS rats. Physiological parameters were measured until 6 wk postsurgery. IIS rats ate less and lost more weight for the first 2 wk postsurgery. At study completion, body weights were not different, but IIS rats had reversed components of the metabolic syndrome. The interposed ileal segment adapted to a more jejunum-like villi length, mucosal surface area, and GATA4/ILBP mRNA. The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi. IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum, suggesting an early and efficient reabsorption of primary bile acids. IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss. There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR, SHP, or NTCP expression. IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling. There is early reabsorption of primary bile acids despite selective “jejunization” of the interposed ileal segment. Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery.
Examining the Genomic Influence of Skin AntioxidantsIn Vitro
Authors: Gruber James V. , Holtz Robert
Published: July 2010

A series of well-known, purified antioxidants including: Resveratrol, Epigallocatechin Gallate (EGCG), Genistein, Rosavin, Puerarin, Chlorogenic Acid, Propolis and two newer unexplored isoflavonoids isolated fromMaclura pomifera(Osage Orange) including Pomiferin and Osajin, were applied to Normal Human Dermal Fibroblasts (NHDF) and Normal Human Dermal Keratinocytes (NHEK) for 24 hours. The resulting treated cells were then examined using human gene microarrays supplied by Agilent. These chips typically have somewhere on the order of 30,000 individual genes which are expressed in the human genome. For our study, this large list of genes was reduced to 205 principal genes thought to be important for skin and each individual ingredient was examined for its influence on the culled list of genes. Working on a hypothesis that there may be some common genes which are either upregulated or downregulated by all or most of these ingredients, a short list of genes for each cell line was developed. What appears to emerge from these studies is that several genes in the gene pool that was screened are influenced by most or all of the molecules of interest. Genes that appear to be upregulated in both cell lines by all the ingredients include: ACLY, AQP3, COX1, NOS3, and PLOD3. Genes that appear to be downregulated in both cell lines by all ingredients include only PGR.
Agreement of Immunoassay and Tandem Mass Spectrometry in the Analysis of Cortisol and Free T4: Interpretation and Implications for Clinicians
Authors: Tractenberg Rochelle E. , Jonklaas Jacqueline , Soldin Steven J.
Published: July 2010

Objective. To quantify differences in results obtained by immunoassays (IAs) and tandem mass spectrometry (MSMS) for cortisol and free thyroxine (FT4).Design&Patients. Cortisol was measured over 60 minutes following a standard ACTH stimulation test (n=80); FT4 was measured over time in two cohorts of pregnant (n=57), and nonpregnant (n=28) women.Measurements. Samples were analyzed with both IA and MSMS.Results. Results for cortisol by the two methods tended to agree, but agreement weakened over the 60-minute test and was worse for higher (more extreme) concentrations. The results for FT4 depended on the method. IA measurements tended to agree with MSMS measurements when values fell within “normal levels”, but agreement was not constant across trimester in pregnant women and was poorest for the extreme (low/high) concentrations. Correlations between MSMS measurements and the difference between MSMS and IA results were strong and positive (0.411<  r  <0.823; allP<.05).Conclusions. IA and MSMS provide different measures of cortisol and FT4 at extreme levels, where clinical decision making requires the greatest precision. Agreement between the methods is inconsistent over time, is nonlinear, and varies with the analyte and concentrations. IA-based measurements may lead to erroneous clinical decisions.
Remote Postoperative Epidural Hematoma after Subdural Hygroma Drainage
Authors: Paiva Wellingson Silva , Oliveira Arthur Maynart Pereira , Andrade Almir Ferreira de , Brock Roger Schmidt , Teixeira Manoel Jacobsen
Published: July 2010

Objective. Subdural hygroma is reported to occur in 5%–20% of all patients with closed head trauma, the treatment is controversial and in symptomatic cases surgical drainage is need. We report on a new case with remote acute epidural hematoma (AEH) after subdural hygroma drainage.Case Presentation. A 38-year-old man suffered blunt head trauma and had diffuse axonal injury grade III in CT scan. A CT scan that was late performed showed an increasing subdural fluid collection with mild mass effect and some effacement of the left lateral ventricle. We perform a trepanation with drainage of a hypertensive subdural collection with citrine aspect. Postoperative tomography demonstrated a large left AEH. Craniotomy and evacuation of the hematoma were performed.Conclusion. The mechanism of remote postoperative AEH formation is unclear. Complete reliance on neurologic monitoring, trust in an early CT scan, and a relative complacency after an apparently successful initial surgery for hygroma drainage may delay the diagnosis of this postoperative AEH.
Application of the Banach Fixed-Point Theorem to the Scattering Problem at a Nonlinear Three-Layer Structure with Absorption
Authors: Serov VS , Schüermann HW , Svetogorova E
Published: July 2010

A method based on the Banach fixed-point theorem is proposed for obtaining certain solutions (TE-polarized electromagnetic waves) of the Helmholtz equation describing the reflection and transmission of a plane monochromatic wave at a nonlinear lossy dielectric film situated between two lossless linear semiinfinite media. All three media are assumed to be nonmagnetic and isotropic. The permittivity of the film is modelled by a continuously differentiable function of the transverse coordinate with a saturating Kerr nonlinearity. It is shown that the solution of the Helmholtz equation exists in form of a uniformly convergent sequence of iterations of the equivalent Volterra integral equation. Numerical results are presented.
Conditional Processes Induced by Birth and Death Processes
Authors: Iizuka Masaru , Tomisaki Matsuyo
Published: July 2010

For birth and death processes with finite state space, we consider stochastic
processes induced by conditioning on hitting the right boundary point before
hitting the left boundary point. We call the induced stochastic processes the
conditional processes. We show that the conditional processes are again birth
and death processes when the right boundary point is absorbing. On the other
hand, it is shown that the conditional processes do not have Markov property
and they are not birth and death processes when the right boundary point is
reflecting.
Determining Boundaries between Abundance Biozones Using Minimal Equipment
Authors: Wilson Brent , Dawe Richard , Gopee Anesh , Grant Sherezz , Kissoon Arianna , Young Taneja , De Noon Chanelle , McLean Annalize , Singh Kala
Published: July 2010

The areal extent of a biological community is usually determined using statistical techniques that only give reliable results where samples contain similar and high numbers of specimens. This paper presents a simple, inexpensive method for determining the geographical limits of biological communities applicable where adjacent samples contain widely differing numbers of specimens. The method is a development of SHE Analysis, which discerns boundaries between adjacent abundance biozones (ABs), an AB being an area with a distinct community structure. As originally conceived, SHEbi(SHE Analysis for the identification of Biozones) commences with species' absolute abundances and works best with large samples of equal sizes. If the variance in (per sample) is high, SHEbimay place AB boundaries in unexpected locations. A modification, based on proportional abundances, is developed here using species' proportional abundances () for each sample where is the number of specimens in theith species in the sample. For intertidal foraminifera from the Caroni Swamp, Trinidad, where , the number of specimens, fluctuates widely between samples, the modification (SHEbip) gives ecologically more sensible results than does traditional SHEbi.
Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 Are Localized Primarily to the Vasculature in Human Primary Solid Cancers
Authors: Smith Neil R. , Baker Dawn , James Neil H. , Ratcliffe Kirsty , Jenkins Martin , Ashton Susan E. , Sproat Graham , Swann Ruth , Gray Neil , Ryan Anderson , Jürgensmeier Juliane M. , Womack Chris
Published: July 2010

Purpose: Vascular endothelial growth factor (VEGF) signaling is key to tumor angiogenesis and is an important target in the development of anticancer drugs. However, VEGF receptor (VEGFR) expression in human cancers, particularly the relative expression of VEGFR-2 and VEGFR-3 in tumor vasculature versus tumor cells, is poorly defined.

Experimental Design: VEGFR-2– and VEGFR-3–specific antibodies were identified and used in the immunohistochemical analysis of human primary cancers and normal tissue. The relative vascular localization of both receptors in colorectal and breast cancers was determined by coimmunofluorescence with vascular markers.

Results: VEGFR-2 and VEGFR-3 were expressed on vascular endothelium but not on malignant cells in 13 common human solid tumor types (n > 400, bladder, breast, colorectal, head and neck, liver, lung, skin, ovarian, pancreatic, prostate, renal, stomach, and thyroid). The signal intensity of both receptors was significantly greater in vessels associated with malignant colorectal, lung, and breast than adjacent nontumor tissue. In colorectal cancers, VEGFR-2 was expressed on both intratumoral blood and lymphatic vessels, whereas VEGFR-3 was found predominantly on lymphatic vessels. In breast cancers, both receptors were localized to and upregulated on blood vessels.

Conclusions: VEGFR-2 and VEGFR-3 are primarily localized to, and significantly upregulated on, tumor vasculature (blood and/or lymphatic) supporting the majority of solid cancers. The primary clinical mechanism of action of VEGF signaling inhibitors is likely to be through the targeting of tumor vessels rather than tumor cells. The upregulation of VEGFR-3 on tumor blood vessels indicates a potential additional antiangiogenic effect for dual VEGFR-2/VEGFR-3–targeted therapy. Clin Cancer Res; 16(14); 3548–61. ©2010 AACR.
Prognostic Significance of Telomerase Polymorphism in Non–Small Cell Lung Cancer
Authors: Catarino Raquel , Araújo António , Coelho Ana , Gomes Mónica , Nogueira Augusto , Lopes Carlos , Medeiros Rui M.
Published: July 2010

Purpose: Lung cancer is the leading cause of death in oncologic patients of western countries, with very low survival rates. Telomerase main components are the catalytic subunit (hTERT) and the RNA template (hTR). A functional polymorphism in the hTERT gene was found in the promoter region (−1327T/C), and individuals homozygous for the −1327C/C genotype present shorter telomere length compared with T-carrier genotypes. Our purpose was to investigate the potential prognostic role of the hTERT functional genetic variant in non–small cell lung cancer (NSCLC) patients.

Experimental Design: We prospectively conducted a study involving 226 patients with NSCLC treated with a first-line chemotherapeutic standard protocol. A follow-up study was undertaken (median follow-up time, 26 months) to evaluate treatment response and overall survival of NSCLC patients. The hTERT −1327T/C genetic variants were analyzed by allelic discrimination with real-time PCR.

Results: Our results indicate an influence of the telomerase genetic variants in the overall survival of NSCLC patients. Cox regression analysis showed a significantly higher median estimated cumulative survival of 26.5 months in T-carrier patients, compared with that of 19.3 months in CC patients (hazard ratio, 0.52; 95% confidence interval, 0.35-0.77; P = 0.001).

Conclusions: Telomerase functional polymorphism in the hTERT gene may contribute as a prognostic factor in NSCLC patients. Our findings indicate that hTERT genetic variants, by modulating telomere length, may confer an advantage in chemotherapy response. The assessment of telomerase genetic variants could supplement prognosis of survival in the course of NSCLC and may be a promising molecular marker of treatment response in these patients. Clin Cancer Res; 16(14); 3706–12. ©2010 AACR.
High Computed Tomographic Correlations between Carotid Canal Dehiscence and High Jugular Bulb in the Middle Ear
Authors: Wang Chih-Hung , Shi Zheng-Ping , Liu Dai-Wei , Wang Hsing-Won , Huang Bor-Rong , Chen Hsin-Chien
Published: July 2010

Both carotid canal dehiscence (CCD) and high jugular bulb (HJB) are thought to increase the potential for disastrous consequences during middle ear surgery. Clinical co-presentation of these two great vessel variants has not yet been described. This study aims to determine the relationship between CCD and HJB based on a computed tomographic (CT) temporal bone evaluation. High-resolution CT scans of 408 temporal bones obtained from 208 adults were recruited. Carotid canal integrity, jugular bulb position, petrous apex pneumatization and the minimal thickness of the carotid canal wall (TCW) facing the tympanic cavity were examined and measured for the incidence of CCD and/or HJB. Other variables including gender, age, laterality and the presence of otitis media or mastoiditis were also collected for analysis. CCD was found in 28 ears (6.9%); 19 of these were found to also have HJB (67.9%). The presence of CCD was significantly correlated with HJB presentation. The minimal TCW in HJB ears was significantly thinner than that of normally positioned jugular bulbs. Moreover, after controlling for other candidate variables, the independent factors of age (younger or older than 50 years) and jugular bulb position (high vs. normal) were found to predict the presence of CCD. In conclusion, HJB tends to coexist with a thinner carotid canal wall. This finding emphasizes the need to be watchful for the coexistence of these two great vessel anomalies when surgeons encounter an aged patient presenting either CCD or HJB during middle ear surgery.
Association of RS2200733 but Not RS10033464 on 4q25 with Atrial Fibrillation Based on the Recessive Model in a Taiwanese Population
Authors: Lee Kun-Tai , Yeh Hi-Yin , Tung Chung-Po , Chu Chih-Sheng , Cheng Kai-Hung , Tsai Wei-Chung , Lu Ye-Hsu , Chang Jan-Gowth , Sheu Sheng-Hsiung , Lai Wen-Ter
Published: July 2010

Objectives: To determine the association between genetic variants on chromosome 4q25 and atrial fibrillation (AF) in a Taiwanese population. Methods: We enrolled 200 patients with AF (mean age: 67 ± 13 years) and 158 controls (mean age: 63 ± 10 years). The genotypes of five SNPs, RS2634073, RS2200733, RS13143308, RS2220427 and RS10033464, were determined using multiplex single base extension methods. Results: The distribution of the RS2200733 and RS10033464 genotypes did not significantly deviate from the Hardy-Weinberg equilibrium in the control group. The distribution of the RS2200733 genotypes differed significantly between the AF group and the controls (p = 0.03), whereas the distribution of the RS10033464 genotypes did not (p = 0.49). At RS2200733, patients with the CC genotype exhibited a 0.45 times higher risk of developing AF than those with the TT genotype (p = 0.02) and a recessive model was suggested (p = 0.01). After adjusting for various covariates, patients with the CC genotype remained recessively associated with a lower risk of developing AF than those with the TT genotype (odds ratio: 0.27, 95% confidence interval: 0.11–0.65; p < 0.01). Conclusions: In the Taiwanese, there is an association between SNP RS2200733 – but not RS10033464 – and the development of AF. Based on a recessive model of inheritance, individuals with SNP RS2200733 genotype CC are at a lesser risk of developing AF.
Pre-Clinical Myocardial Metabolic Alterations in Chronic Kidney Disease
Authors: Fink Jeffrey C. , Lodge Martin A. , Smith Mark F. , Hinduja Anish , Brown Jeanine , Dinits-Pensy Mara Y. , Dilsizian Vasken
Published: July 2010

The risk for cardiovascular events conferred by decreased renal function is curvilinear with exponentially greater increases in risk as estimated glomerular filtration rate (eGFR) declines. In 13 non-diabetic pre-dialysis chronic kidney disease (CKD) patients, we employed quantitative F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) as a means to measure myocardial metabolic changes. Methods: Dynamic cardiac FDG PET images were acquired after 6 h fasting and glucose loading. Corrections for attenuation, scatter, randoms, dead time and decay were applied to the PET data and myocardial glucose utilization (MGU) was calculated using the Patlak method in conjunction with standardized myocardial regions of interest and an image-derived input function (left atrium). MGU was compared with eGFR based on a serum creatinine drawn within 2 weeks of the study date. Results: MGU was relatively uniform between the myocardial sectors (coefficient of variation = 16.2 ± 6.8%) within each patient. Between patients, whole myocardium MGU varied considerably with a range of 37.3–156.2 µmol/min/100 g and a mean of 68.9 ± 38.3 µmol/min/ 100 g. eGFR ranged from 11–89 ml/min/1.73 m2 with a mean of 42.8 ± 26.9 ml/min/1.73 m2. There was an inverse correlation between whole myocardium MGU and eGFR (Spearman’s rho correlation = –0.615, p = 0.025). In multivariate analysis, the relationship between MGU and eGFR was sustained with adjustment for age, race and gender (adjusted β = –1.56 ± 0.48, p = 0.01). There was no correlation between cardiac workload and eGFR (p = NS). Conclusions: A significant inverse correlation between MGU and eGFR is supportive of the hypothesis that CKD is associated with myocardial metabolic changes, which could not be attributed to demographic factors or cardiac workload. Dynamic FDG PET could provide a sensitive, non-invasive, quantitative tool for investigating pre-clinical myocardial abnormalities in patients with CKD.
Late and Very Late Drug-Eluting Stent Malapposition
Authors: Kang Soo-Jin , Mintz Gary S. , Park Duk-Woo , Lee Seung-Whan , Kim Young-Hak , Lee Cheol Whan , Han Ki-Hoon , Kim Jae-Joong , Park Seong-Wook , Park Seung-Jung
Published: July 2010

Background—

The long-term natural history of acquired malapposition continues to be the subject of debate.

Methods and Results—

Using volumetric intravascular ultrasound analyses, we evaluated serial (poststenting, 6-month, and 2-year follow-up) changes in drug-eluting stent–treated vascular segments with acquired malapposition. External elastic membrane, stent, lumen, malapposition, and peristent plaque+media (P+M=external elastic membrane −stent− malapposition) areas were measured; and volumes were calculated and divided by stent length (normalized volume). Among 250 lesions in which complete serial intravascular ultrasound data were available, stent malapposition was identified in 19 lesions (7.6%) at 6 months, and an additional 13 malapposition lesions were newly detected at 2 years (5.2%). Because no malapposition sites resolved, the malapposition rate at 2 years was 12.8%. Malapposition areas and volumes were correlated to the increases in external elastic membrane (positive remodeling) throughout the study period, from immediately after stenting to 6 months and from 6 months to 2 years, both in the group that developed malapposition at 6 months and in the group that developed malapposition at 2 years. Clinical follow-up beyond the 2 year intravascular ultrasound study was done in all patients. Overall, there were 2 cardiac deaths and 1 noncardiac death. Two patients presented with acute myocardial infarction associated with very late stent thrombosis (1 definite stent thrombosis, 1 probable stent thrombosis). Three patients underwent repeat revascularization owing to in-stent restenosis developed after the 2-year follow-up.

Conclusions—

Expansive vascular remodeling may play a role in the development and dynamic progression of acquired drug-eluting stent malapposition, not only during the first 6 months after implantation but thereafter.
Percutaneous Coronary Intervention in the Elderly
Authors: Johnman Cathy , Oldroyd Keith G. , Mackay Danny F. , Slack Rachel , Pell Alastair C.H. , Flapan Andrew D. , Jennings Kevin P. , Eteiba Hany , Irving John , Pell Jill P.
Published: July 2010

Background—

The elderly account for an increasing proportion of the population and have a high prevalence of coronary heart disease. Percutaneous coronary intervention (PCI) is the most common method of revascularization in the elderly. We examined whether the risk of periprocedural complications after PCI was higher among elderly (age ≥75 years) patients and whether it has changed over time.

Methods and Results—

The Scottish Coronary Revascularization Register was used to undertake a retrospective cohort study on all 31 758 patients undergoing nonemergency PCI in Scotland between April 2000 and March 2007, inclusive. There was an increase in the number and percentage of PCIs undertaken in elderly patients, from 196 (8.7%) in 2000 to 752 (13.9%) in 2007. Compared with younger patients, the elderly were more likely to have multivessel disease, multiple comorbidity, and a history of myocardial infarction or coronary artery bypass grafting (χ
2
tests, all
P
<0.001). The elderly had a higher risk of major adverse cardiovascular events within 30 days of PCI (4.5% versus 2.7%, χ
2
test
P
<0.001). Over the 7 years, there was a significant increase in the proportion of elderly patients who had multiple comorbidity (χ
2
test for trend,
P
<0.001). Despite this, the underlying risk of complications did not change significantly over time either among the elderly (χ
2
test for trend,
P
=0.142) or overall (χ
2
test for trend,
P
=0.083).

Conclusions—

Elderly patients have a higher risk of periprocedural complications and account for an increasing proportion of PCIs. Despite this, the risk of complications after PCI has not increased over time.
Safety and Efficacy of the Subclavian Approach for Transcatheter Aortic Valve Implantation With the CoreValve Revalving System
Authors: Petronio Anna Sonia , De Carlo Marco , Bedogni Francesco , Marzocchi Antonio , Klugmann Silvio , Maisano Francesco , Ramondo Angelo , Ussia Gian Paolo , Ettori Federica , Poli Arnaldo , Brambilla Nedy , Saia Francesco , De Marco Federico , Colombo Antonio
Published: July 2010

Background—

Transcatheter aortic valve implantation (TAVI) is a new option for patients with severe aortic stenosis at high surgical risk. The standard retrograde approach through the femoral artery is contraindicated in case of unfavorable iliofemoral anatomy or extensive disease. In these patients, a trans-subclavian approach may be feasible.

Methods and Results—

Between June 2007 and July 2009, TAVI with the CoreValve bioprosthesis (Medtronic, Minneapolis, Minn) was performed in 514 consecutive patients at 13 Italian hospitals, using the subclavian approach in 54 cases. The median logistic EuroSCORE was significantly higher in the subclavian (19.4; interquartile range, 12.5 to 29.8) versus femoral group (25.3; interquartile range, 15.1 to 36.6) (
P
=0.03), as well as the rate of comorbidities. Procedural success was obtained in 100% versus 98.4% of the subclavian versus femoral groups, respectively (
P
=0.62), with intraprocedural mortality of 0% versus 0.9% (
P
=1.00). The most common in-hospital complications were a new left bundle-branch block (22.4%) and the need for pacemaker (16.3%). No specific complications for the subclavian access (vessel rupture, vertebral or internal mammary ischemia) were reported. The learning curve for the subclavian approach led to a wider use of local anesthesia. Thirty-day mortality was 0% versus 6.1% in the subclavian versus femoral groups, respectively (
P
=0.13). Six-month mortality rate was 9.4% versus 15.8% (
P
=0.44), whereas valve-related adverse events were 13.6% versus 13.9% (
P
=0.79).

Conclusions—

TAVI through the subclavian approach appeared feasible and safe, with excellent procedural success and low in-hospital complication rates. This new technique allows patients with contraindications to the femoral approach to be treated with TAVI.
Relationship of Intraoperative Cerebral Oxygen Saturation to Neurodevelopmental Outcome and Brain Magnetic Resonance Imaging at 1 Year of Age in Infants Undergoing Biventricular Repair
Authors: Kussman Barry D. , Wypij David , Laussen Peter C. , Soul Janet S. , Bellinger David C. , DiNardo James A. , Robertson Richard , Pigula Frank A. , Jonas Richard A. , Newburger Jane W.
Published: July 2010

Background—

Near-infrared spectroscopy monitoring of cerebral oxygen saturation (rS
o
2
) has become routine in many centers, but no studies have reported the relationship of intraoperative near-infrared spectroscopy to long-term neurodevelopmental outcomes after cardiac surgery.

Methods and Results—

Of 104 infants undergoing biventricular repair without aortic arch reconstruction, 89 (86%) returned for neurodevelopmental testing at 1 year of age. The primary near-infrared spectroscopy variable was the integrated rS
o
2
(area under the curve) for rS
o
2
≤45%; secondary variables were the average and minimum rS
o
2
by perfusion phase and at specific time points. Psychomotor and mental development indexes of the Bayley scales, head circumference, neurological examination, and abnormalities on brain magnetic resonance imaging did not differ between subjects according to a threshold level for rS
o
2
of 45%. Lower Psychomotor Development Index scores were modestly associated with lower average (
r
=0.23,
P
=0.03) and minimum (
r
=0.22,
P
=0.04) rS
o
2
during the 60-minute period after cardiopulmonary bypass but not with other perfusion phases. Hemosiderin foci on brain magnetic resonance imaging were associated with lower average rS
o
2
from postinduction to 60 minutes post cardiopulmonary bypass (71±10% versus 78±6%,
P
=0.01) and with lower average rSO
2
during the rewarming phase (72±12% versus 83±9%,
P
=.003) and during the 60-minute period following cardiopulmonary bypass (65±11% versus 75±10%,
P
=0.009). In regression analyses that adjusted for age ≤30 days, Psychomotor Development Index score (
P
=0.02) and brain hemosiderin (
P
=0.04) remained significantly associated with rS
o
2
during the 60-minute period following cardiopulmonary bypass.

Conclusions—

Perioperative periods of diminished cerebral oxygen delivery, as indicated by rS
o
2
, are associated with 1-year Psychomotor Development Index and brain magnetic resonance imaging abnormalities among infants undergoing reparative heart surgery.

Clinical Trial Registration—

URL: http://clinicaltrials.gov. Unique identifier: NCT00006183.
Relation of Platelet and Leukocyte Inflammatory Transcripts to Body Mass Index in the Framingham Heart Study
Authors: Freedman Jane E. , Larson Martin G. , Tanriverdi Kahraman , O'Donnell Christopher J. , Morin Kristine , Hakanson Amanda S. , Vasan Ramachandran S. , Johnson Andrew D. , Iafrati Mark D. , Benjamin Emelia J.
Published: July 2010

Background—

Although many genetic epidemiology and biomarker studies have been conducted to examine associations of genetic variants and circulating proteins with cardiovascular disease and risk factors, there has been little study of gene expression or transcriptomics. Quantitative differences in the abundance of transcripts has been demonstrated in malignancies, but gene expression from a large community-based cohort examining risk of cardiovascular disease has never been reported.

Methods and Results—

On the basis of preliminary microarray data and previously suggested genes from the literature, we measured expression of 48 genes by high-throughput quantitative reverse-transcriptase polymerase chain reaction in 1846 participants of the Framingham Offspring cohort from RNA derived from isolated platelets and leukocytes. A multivariable stepwise regression model was used to assess clinical correlates of quantitative RNA expression. For specific inflammatory platelet-derived transcripts, including
ICAM1
,
IFNG
,
IL1R1
,
IL6
,
MPO
,
COX2
,
TNF
,
TLR2
, and
TLR4
, there were significant associations with higher body mass index (BMI). Compared with platelets, fewer leukocyte-derived transcripts were associated with BMI or other cardiovascular risk factors. Select transcripts were found to be highly heritable, including
GPIBA
and
COX1
. Almost uniformly, heritable transcripts were not those associated with BMI.

Conclusions—

Inflammatory transcripts derived from platelets, particularly those part of the nuclear factor κ B pathway, are associated with BMI, whereas others are heritable. This is the first study, using a large community-based cohort, to demonstrate clinical correlates of gene expression and is consistent with the hypothesis that specific peripheral-blood transcripts play a role in the pathogenesis of coronary heart disease and its risk factors.
Potential Effects of Aggressive Decongestion During the Treatment of Decompensated Heart Failure on Renal Function and Survival
Authors: Testani Jeffrey M. , Chen Jennifer , McCauley Brian D. , Kimmel Stephen E. , Shannon Richard P.
Published: July 2010

Background—

Overly aggressive diuresis leading to intravascular volume depletion has been proposed as a cause for worsening renal function during the treatment of decompensated heart failure. If diuresis occurs at a rate greater than extravascular fluid can refill the intravascular space, the concentration of such intravascular substances as hemoglobin and plasma proteins increases. We hypothesized that hemoconcentration would be associated with worsening renal function and possibly would provide insight into the relationship between aggressive decongestion and outcomes.

Methods and Results—

Subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial limited data set with a baseline/discharge pair of hematocrit, albumin, or total protein values were included (336 patients). Baseline-to-discharge increases in these parameters were evaluated, and patients with ≥2 in the top tertile were considered to have evidence of hemoconcentration. The group experiencing hemoconcentration received higher doses of loop diuretics, lost more weight/fluid, and had greater reductions in filling pressures (
P
<0.05 for all). Hemoconcentration was strongly associated with worsening renal function (odds ratio, 5.3;
P
<0.001), whereas changes in right atrial pressure (
P
=0.36) and pulmonary capillary wedge pressure (
P
=0.53) were not. Patients with hemoconcentration had significantly lower 180-day mortality (hazard ratio, 0.31;
P
=0.013). This relationship persisted after adjustment for baseline characteristics (hazard ratio, 0.16;
P
=0.001).

Conclusion—

Hemoconcentration is significantly associated with measures of aggressive fluid removal and deterioration in renal function. Despite this relationship, hemoconcentration is associated with substantially improved survival. These observations raise the question of whether aggressive decongestion, even in the setting of worsening renal function, can positively affect survival.
Impaired Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Activation and Ischemic Recovery in the Senescent Heart
Authors: Ma Heng , Wang Jingying , Thomas D. Paul , Tong Chao , Leng Lin , Wang Wenkui , Merk Melanie , Zierow Swen , Bernhagen Jürgen , Ren Jun , Bucala Richard , Li Ji
Published: July 2010

Background—

Elderly patients are more sensitive than younger patients to myocardial ischemia, which results in higher mortality. We investigated how aging affects the cardioprotective AMP-activated protein kinase (AMPK) signaling pathway.

Methods and Results—

Ischemic AMPK activation was impaired in aged compared with young murine hearts. The expression and secretion of the AMPK upstream regulator, macrophage migration inhibitory factor (MIF), were lower in aged compared with young adult hearts. Additionally, the levels of hypoxia-inducible factor 1α, a known transcriptional activator of MIF, were reduced in aged compared with young hearts. Ischemia-induced AMPK activation in MIF knockout mice was blunted, leading to greater contractile dysfunction in MIF-deficient than in wild-type hearts. Furthermore, intramyocardial injection of adenovirus encoding MIF in aged mice increased MIF expression and ischemic AMPK activation and reduced infarct size.

Conclusions—

An impaired MIF-AMPK activation response in senescence thus may be attributed to an aging-associated defect in hypoxia-inducible factor 1α, the transcription factor for MIF. In the clinical setting, impaired cardiac hypoxia-inducible factor 1α activation and consequent reduced MIF expression may play an important role in the increased susceptibility to myocardial ischemia observed in older cardiac patients.
Sudden Cardiac Death in End-Stage Renal Disease Patients
Authors: Wang Angela Yee-Moon , Lam Christopher Wai-Kei , Chan Iris Hiu-Shuen , Wang Mei , Lui Siu-Fai , Sanderson John E.
Published: July 2010

End-stage renal disease patients experience a high incidence of sudden cardiac death. We performed a 5-year prospective study in 230 end-stage renal disease patients, aiming to determine the role of echocardiography and the additional value of serum biomarkers in predicting sudden cardiac death. During follow-up, 24% of all deaths were attributed to sudden cardiac death. In the multivariable Cox regression analysis considering clinical, biochemical, dialysis, and echocardiographic parameters, left ventricular systolic dysfunction emerged as the most significant predictor of sudden cardiac death, followed by a high systolic and a low diastolic blood pressure. An ejection fraction cutoff ≤48.0% is associated with a specificity of 78.6% and a sensitivity of 57.7% in predicting sudden cardiac death. In biomarker-based multivariable Cox regression analysis, N-terminal probrain natriuretic peptide displays an independent association with sudden cardiac death and is more significantly associated with sudden cardiac death than cardiac troponin T. In the combined echocardiography and biomarker-based multivariable Cox regression model, N-terminal probrain natriuretic peptide loses significance to left ventricular ejection fraction, whereas cardiac troponin T retains a significant association with sudden cardiac death independent of echocardiographic parameters. In conclusion, systolic dysfunction is the most significant predictor of sudden cardiac death followed by a high systolic and a low diastolic blood pressure. Our data suggest additional value in measuring cardiac troponin T for sudden cardiac death risk stratification. N-terminal probrain natriuretic peptide may be used in place of echocardiography to identify patients at risk of sudden cardiac death but had no added value over echocardiography in predicting sudden cardiac death.
Equine Estrogens Impair Nitric Oxide Production and Endothelial Nitric Oxide Synthase Transcription in Human Endothelial Cells Compared With the Natural 17β-Estradiol
Authors: Novensa Laura , Selent Jana , Pastor Manuel , Sandberg Kathryn , Heras Magda , Dantas Ana Paula
Published: July 2010

Conjugated equine estrogen therapy is the most common hormone replacement strategy used to treat postmenopausal women. However, the ability of an individual conjugated equine estrogen to modulate NO production and, therefore, to induce cardiovascular protection is largely unknown. The effects of equine and naturally occurring estrogens on NO generation were evaluated in human aortic endothelial cells by measuring in vivo NO production, as well as NO synthase (eNOS) activity and expression. The transcriptional activity on the eNOS gene was determined by the ability of estrogen receptors (α and β) to activate the eNOS promoter and induce transcription. Docking and molecular dynamics simulations were used to study structural features of the interaction between estrogenic compounds and estrogen receptor-α. After 24 hours of incubation, we found that estrone upregulated NO production almost as effectively as estradiol by increasing eNOS activity and expression. However, the effect of equine estrogens (equilin, equilenin, and their metabolites) were marked decreased. eNOS promoter activity by equine estrogens was 30% to 50% lower than the naturally occurring estrogens. Computational analysis of estrogen molecules revealed that position 17 and the saturation of estrogenic compounds in ring B are important determinants for estrogen receptor-α transcriptional activity. Equine estrogens increase NO production less effectively than naturally occurring estrogens, partially because of their lesser ability to activate the eNOS promoter and induce transcription. Differences in NO production by different estrogens may account for the differences in cardiovascular benefits achieved by the distinct estrogen replacement therapies.
Angiotensin-Converting Enzyme Inhibition Augments Coronary Release of Tissue Plasminogen Activator in Women But Not in Men
Authors: Matsumoto Tetsuya , Takashima Hiroyuki , Nakae Ichiro , Yamane Tetsunobu , Hayashi Hideki , Horie Minoru
Published: July 2010

The renin-angiotensin system regulates the vascular fibrinolytic balance. In the human forearm vasculature, angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) increase the release of t-PA through endogenous bradykinin. We tested the hypothesis that ACE inhibition and sex modulate the endogenous coronary release of tissue plasminogen activator (t-PA) in hypertensive patients. Seventy-three patients underwent diagnostic coronary angiography and had normal coronary angiograms. Thirty-three patients (21 men and 12 women) were treated with imidapril (5 mg/day) for 4 weeks (ACE-I group), and 40 (23 men and 17 women) were not treated with ACE-I (non–ACE-I group). All of the women were postmenopausal. Coronary blood flow in the left anterior descending artery was evaluated by measuring Doppler flow velocity. Net coronary t-PA release was determined as (coronary sinus−aorta gradient of t-PA)×(coronary blood flow)×[(100−hematocrit)/100]. Age, arterial pressure, heart rate, lipid levels, coronary flow, and the plasma level of t-PA at either aorta or coronary sinus were comparable among the 4 groups. In women, net t-PA release in the ACE-I group was significantly higher than that in the other groups (
P
<0.05; man non–ACE-I group: 1.4±2.6 ng/mL; woman non–ACE-I group: 1.4±3.1 ng/mL; man ACE-I group: −1.8±2.8 ng/mL; woman ACE-I group: 14.8±3.6 ng/mL). Correction for smoking status gave similar results. There was a significant negative correlation between serum ACE activity and coronary t-PA release in women (
r
=−0.38;
P
<0.05) but not in men. ACE inhibition increases coronary release of t-PA in women but not in men.
Large-Margin Classification in Infinite Neural Networks
Authors: Cho Youngmin , Saul Lawrence K.
Published: July 2010

We introduce a new family of positive-definite kernels for large margin classification in support vector machines (SVMs). These kernels mimic the computation in large neural networks with one layer of hidden units. We also show how to derive new kernels, by recursive composition, that may be viewed as mapping their inputs through a series of nonlinear feature spaces. These recursively derived kernels mimic the computation in deep networks with multiple hidden layers. We evaluate SVMs with these kernels on problems designed to illustrate the advantages of deep architectures. Compared to previous benchmarks, we find that on some problems, these SVMs yield state-of-the-art results, beating not only other SVMs but also deep belief nets.
On a Stochastic Leaky Integrate-and-Fire Neuronal Model
Authors: Buonocore A. , Caputo L. , Pirozzi E. , Ricciardi L.M.
Published: July 2010

The leaky integrate-and-fire neuronal model proposed in Stevens and Zador ( 1998 ), in which time constant and resting potential are postulated to be time dependent, is revisited within a stochastic framework in which the membrane potential is mathematically described as a gauss-diffusion process. The first-passage-time probability density, miming in such a context the firing probability density, is evaluated by either the Volterra integral equation of Buonocore, Nobile, and Ricciardi ( 1987 ) or, when possible, by the asymptotics of Giorno, Nobile, and Ricciardi ( 1990 ). The model examined here represents an extension of the classic leaky integrate-and-fire one based on the Ornstein-Uhlenbeck process in that it is in principle compatible with the inclusion of some other physiological characteristics such as relative refractoriness. It also allows finer tuning possibilities in view of its accounting for certain qualitative as well as quantitative features, such as the behavior of the time course of the membrane potential prior to firings and the computation of experimentally measurable statistical descriptors of the firing time: mean, median, coefficient of variation, and skewness. Finally, implementations of this model are provided in connection with certain experimental evidence discussed in the literature.
Lassen Die Empfehlungen Der Vereinten Nationen Rückschlüsse Auf Die Rechtliche Natur Der Empfehlungen Des Europarates Und Des Nordischen Rates Zu?
Authors: Nagel Heinrich
Published: July 2010

Die Empfehlungen der Vereinten Nationen haben einige Tradition erlangt, nachdem sie schon im Völkerbunde eine Rolle gespielt hatten. Mit dem Entstehen neuer internationaler Organisation mussten die Empfehlungen schon dadurch an Bedeutung gewinnen, dass sie oft das einzige Mittel sind, wodurch sich diese neuen Organisation überhaupt Geltung verschaffen können. Es ist deshalb auch nicht verwunderlich, dass die Diskussion über die völkerrechtliche Bedeutung der Empfehlungen nicht beendet ist.1) Hierzu soll aus der Fragestellung des Themas ein Beitrag versucht werden, nämlich ob und gegebenfalls welche Rückschlosse aus den Empfehlungen der Vereinten Nationen auf die rechtliche Natur derjeningen des Europarates und des Nordichen Rates2) gezogen werden können.
Den Norsk-Svenske Rengræsnings-Kommission Af 28. Februar I964
Authors: Svenningsen Nils
Published: July 2010

Tidsskriftets redaktor har af undertegnede ønsket en artikel om baggrunden for og formÅlet med den kommission, som den svenske og den norske regering i begyndelsen af 1964 har nedsat til behandling af rengræsningsspørgsmÅlet i Nordskandinavien. Til imødekommen af dette ønske vil det være hensigtsmæssigt først at meddele nogle orienterende oplysninger om visse fakta vedrorende selve substansen af nævnte problem og derefter, ved hjælp af officielt kildemateriale, i store træk at give en historik af udviklingen i den kæde af norsk-svenske forhandlinger og overenskomster om dette emne, som de sidste par hundrede År opviser, for sÅ til slut at gore rede for den nu siddende kommissions tilblivelse, dens mandat og dens formÅl.
Bestämning av flyktingskap i Sverige
Authors: Nobel Peter
Published: July 2010

There is no official refugee declaration in Sweden. The procedure is the same for asylum seekers and for other aliens applying for residence permissions. It starts with interrogation by the police, the protocole of which is submitted to the Central Immigration Authority, Statens Invandrarverk SIV. A well functioning legal aid system grants the asylum seeker threatened by expulsion free legal counsel and representation from the stage of the police hearing until the case is finally decided. SIV handles the cases in camera without hearings or contradictionary proceedings. This - according to the author - is the root of a certain credibility gap concerning the information available to SIV and how and to what extent it should be communicated to the applicant. The same is said about the interpretation of refugee law tending to be too restrictive. Negative decisions are combined with an order of expulsion. They do often give some explanation of the reasons for the decision. There is an absolute right of appeal to be lodged with the Government within three weeks. In spite of the absence of a refugee declaration there is categorizing into A- or convention refugees — entitled to CTDs, B-refugees and others. This is important for the refugees opportunity to employmant, education etc. but there is no appeal or appropriate remedy in these issues. Considering this and the psychological feeling of safety for the asylum seeker, it is felt that refugee declarations should be introduced in the swedish system. A proposal to establish a special board of appeal for refugee- and other alien cases separated from the Government, has been rejected in Sweden. Therefore the last resort remains the Government, a political instance. This is considered to be to the advantage of refugees - but only as long as the political climate in the country is favourable to them.