bluuebunny/crossref_metadata_2025 huggingface dataset:
Rotavirus Genotypes in Costa Rica, Nicaragua, Honduras and the Dominican Republic
Authors: Bourdett-Stanziola Lurys , Ortega-Barria Eduardo , Espinoza Felix , Bucardo Filemon , Jimenez Carlos , Ferrera Annabelle
Published: August 2010

In this study, 574 stool samples from children with gastroenteritis were obtained from different hospitals in Costa Rica, Honduras, Nicaragua and the Dominican Republic during 2005–2006. Diarrhea stool samples were analyzed for rotavirus (RV) by ELISA and typed by the RT-PCR-based method. Unusual strains were detected: G1P6, G2P8, G3P6, G9P4, and mixed infections. Recent studies have indicated that unusual human RV strains are emerging as global strains, which has important implications for effective vaccine development. In this context, the next generation of RV vaccines will need to provide adequate protection against diseases caused not only by mixed infections, but also by unusual G/P combinations.
Seroprevalence and Genotype of Hepatitis C Virus among Immigrant Workers from Cambodia and Myanmar in Thailand
Authors: Akkarathamrongsin Srunthron , Praianantathavorn Kesmanee , Hacharoen Nisachol , Theamboonlers Apiradee , Tangkijvanich Pisit , Poovorawan Yong
Published: August 2010

Objective: There is a large number of immigrant workers from Cambodia and Myanmar in Thailand. The aim of our study was to determine seroprevalence and genotypes of hepatitis C virus (HCV) in this group. Methods: Immigrants aged between 15 and 60 years (1,431 Cambodians and 1,594 Myanmarese) were recruited into this study. Each sample was screened for anti-HCV by ELISA. RNA was extracted from seropositive samples and RT-PCR was performed in order to amplify the HCV core region. Each sample was subsequently sequenced, and the genotype was determined by phylogenetic analysis. Results: The prevalence of HCV infection in immigrant workers from Cambodia and Myanmar was 33 (2.3%) and 27 (1.69%) samples, respectively. Of the anti-HCV-positive individuals, 25 (75.8%) from Cambodia and 15 (55.6%) from Myanmar harbored viral RNA. Phylogenetic analysis showed that the predominant HCV genotypes in this group were 1a, 1b, 3a, 3b and 6 (6e, 6f, 6m, 6p and 6r). Most HCV isolates can be found in Thailand, though some subtypes of HCV-6 are uncommon. Conclusions: This study shows the HCV seroprevalence and genotypes among immigrant Cambodians and Myanmarese which may reflect the prevalence in each country and closely relate to the prevalence in the guest country.
Expression of E1E2 on Hepatitis C RNA-Containing Particles Released from Primary Cultured Human Hepatocytes Derived from Infected Cirrhotic Livers
Authors: Ndongo Ndiémé , Selliah Subjini , Berthillon Pascale , Raymond Valérie-Ann , Trépo Christian , Bilodeau Marc , Petit Marie-Anne
Published: August 2010

Objective: To determine whether liver-derived hepatitis C RNA-containing particles express the E1E2 discontinuous antigenic determinant defined by unique monoclonal antibody (mAb) D32.10 which recognizes three highly conserved segments in E1 (aa297–306) and E2 (aa480–494 and aa613–621) envelope glycoproteins. Methods: Human hepatocytes were isolated from HCV-infected cirrhotic explanted livers. The liver-derived hepatitis C virus (HCV) particles released from three distinct cultures (genotypes 1b and 2b) were characterized. HCV RNA+ was quantified by real-time RT-PCR. The E1E2 antigenic activity was assessed by indirect ELISA and immunoblotting using D32.10. The density distributions of HCV RNA and E1E2 antigen were determined by isopycnic sucrose density gradients. HCV E1E2, E2 and core antigens were detected in the cells by immunochemical staining. Results: Liver-derived HCV particles contained HCV RNA (106–107 copies/mg of protein) and core proteins and expressed the E1E2/D32.10 epitope. HCV RNA and E1E2 cosedimented between 1.15 and 1.25 g/ml in sucrose gradients. Moreover, the mAb D32.10 detected E1E2 by immunostaining in HCV-infected hepatocytes in parallel with E2 and core antigens. Conclusion: Our results provide evidence that the mAb D32.10 recognizes E1E2 envelope complexes expressed in the cell cytoplasm and on the surface of HCV RNA-containing particles released from short-term cultures of in vivo infected hepatocytes.
Human Herpesvirus 7 in Allogeneic Hemopoietic Stem Cell Transplant Recipients in the Central Clinical Hospital in Warsaw: A Three-Year Survey
Authors: Dzieciatkowski Tomasz , Przybylski Maciej , Basak Grzegorz Wladyslaw , Torosian Tigran , Jedrzejczak Wieslaw Wiktor , Mlynarczyk Grazyna
Published: August 2010

Objectives: Human herpesvirus 7 (HHV-7) is spread worldwide and has been described as a potential pathogen in immunosuppressed patients. Different clinical manifestations have been described including fever and skin rash; HHV-7 may also be a possible cofactor for cytomegalovirus disease in transplant recipients. Materials and Methods: A retrospective review of a group of 58 adult recipients of allogeneic hemopoietic stem cell transplantation was made. Serum samples taken in the range of 0–180 days after transplant were examined for presence of specific HHV-7 sequences using the quantitative real-time PCR method. Results: HHV-7 DNA was detected in plasma samples in 26 (45%) of the 58 recipients between day 20 and day 65 of transplantation. All of them developed fever of unknown origin; also HHV-5 DNA was detected in plasma samples collected from 11 HHV-7-positive patients. None of the described individuals died during detectable HHV-7 or HHV-5 viremia periods. Conclusions: There is a high frequency of detectable HHV-7 viral load in allogeneic stem cell transplant recipients in Poland. Limited availability and sensitivity of serological methods along with the necessity of rapid introduction of antiviral treatment has forced the development of molecular diagnostics. Furthermore, establishment of appropriate procedures for monitoring active HHV-7 infection is important to clarify the virus infection in transplant recipients.
Extended Phylogeny of the Equine Arteritis Virus Sequences Including South American Sequences
Authors: Metz Germán Ernesto , Ocampos Giselle Paula Martín , Serena María Soledad , Gambaro Sabrina Eliana , Nosetto Edgardo , Echeverría María Gabriela
Published: August 2010

Objective: To perform genetic analysis of the ORF5 of equine arteritis virus (EAV) may provide new insights into the genetic evolution and origin of the Argentinean EAV sequences. Methods: A total of 76 sequences were analyzed by neighbor joining (NJ), maximum parsimony and maximum likelihood algorithms. The analysis of the selective pressures was performed using the Tajima’s test. Results: The trees showed similar topologies. Two clades were identified: the first clade was formed by strains isolated mainly from a donkey, whereas the second clade presented four large groups from different geographic regions exclusively from Equus caballus. In this clade, we identified a group formed by South African and another one by South American and European sequences. In the latter, the monophyletic group was formed by seven Argentinean sequences. In the NJ tree, we identified a group formed by six Argentinean sequences. The Tajima’s test showed a D value of 1.73663, indicating that the sequences analyzed follow a neutral evolution model. Conclusion: We concluded that the Argentinean sequences have a paraphyletic origin and that the fixation of point mutation might follow the neutral model evolution; however, we identified purifying pressures that may be involved in the differentiation of the EAV sequences.
Still Sad after Successful Renal Transplantation: Are We Failing to Recognise Depression? An Audit of Depression Screening in Renal Graft Recipients
Authors: Spencer Benjamin Walter Jack , Chilcot Joseph , Farrington Ken
Published: August 2010

Background: Depression is common in chronic physical illness, including renal graft recipients. There is evidence that depression is an independent marker of poorer prognosis in dialysis patients. In the UK, screening is advocated by the National Institute for Health and Clinical Excellence guidelines, and validated screening tools exist, such as the Beck Depression Inventory (BDI). Methods: We audited our renal graft recipient outpatient clinic to see if screening was being undertaken by our clinicians, and to confirm the rates of depressive symptoms in our population as reported by the BDI. Results: In a sample of 58 transplant patients, we found that the screening rate for depression was poor, particularly by nephrologists (n = 8, 13.8%). In addition, 13 (22.4%) of our patients had significant depressive symptoms (BDI score ≧16). Following univariate analysis, we found that the most important predictor of current significant depressive symptoms was a past history of depression. Conclusions: Despite the limitations of our small audit, our results confirm that depression is under-screened in renal graft recipients, even in those with a known history of depression. We recommend increased awareness of depression and implementation of regular screening in an outpatient setting; in this regard, the BDI may have utility.
Low iPTH Can Predict Vascular and Coronary Calcifications in Patients Undergoing Peritoneal Dialysis
Authors: Kim Sun Chul , Kim Hye Won , Oh Se Won , Yang Ha Na , Kim Myung-Gyu , Jo Sang-Kyung , Cho Won Yong , Kim Hyoung Kyu
Published: August 2010

Background: There is substantial evidence that low levels of serum intact parathyroid hormone (iPTH) are associated with vascular calcium deposition and subsequent increased cardiovascular risk in chronic kidney disease patients. The purpose of this study was to determine the relationship between the serum iPTH level, and vascular and coronary artery calcifications (VCs, CACs) and arterial stiffness in peritoneal dialysis (PD) patients. Methods: In this cross-sectional study, 93 PD patients were included. VCs, CACs and arterial stiffness were measured by simple X-rays of the hands and pelvis, multi-slice coronary CT and brachial-ankle pulse wave velocity (BaPWV). Results: Patients were divided into 3 groups according to iPTH levels. The prevalence of severe VCs (VC score ≧3) was highest in the low iPTH group (<150 pg/ml). In multivariate analysis, the presence of diabetes mellitus and a low iPTH were shown to be significant risk factors for severe VCs. In addition, a simple VC score of ≧1 was a significant variable for predicting severe CACs (CAC score ≧400). Conclusion: Low iPTH and the presence of diabetes mellitus are thought to be independent risk factors for predicting VCs. VCs determined by simple X-ray can further predict the coexistence of CACs that ultimately might contribute to increased cardiovascular risk in PD patients.
Role of the Parathyroid Gland Vascularization Index in Predicting Percutaneous Ethanol Injection Efficacy in Refractory Uremic Hyperparathyroidism
Authors: Chen Han-Hsiang , Lu Kuo-Cheng , Lin Cheng-Jui , Wu Chih-Jen
Published: August 2010

Aims: To evaluate the role of the quantitative vascularization index (VI) as a measure of the completeness of percutaneous ethanol injection therapy (PEIT). Methods: A total of 37 dialysis patients with secondary hyperparathyroidism refractory to medical therapy received PEIT. We analyzed the role of a quantitative marker of parathyroid adenoma activity, i.e. VI, flow index and vascular flow index as measured by 3-dimensional Doppler ultrasound with a 3-dimensional histogram software, for all patients before treatment and at 1 month and 6 months after PEIT. Results: Serum intact parathyroid hormone (i-PTH) level showed a strong positive correlation with the VI both before (p < 0.001) and after (p < 0.001) PEIT. There was no correlation between i-PTH level and the volume of the gland either before (p = 0.697) or after (p = 0.564) PEIT. One month after PEIT, 20 patients (group 1) reached the target of i-PTH ≤300 pg/ml and 17 patients (group 2) did not. Group 2 patients had significantly greater VI and i-PTH prior to PEIT than group 1 patients (42.23 ± 8.38 vs. 14.95 ± 8.07, p <0.001 and 1,447 ± 243 vs. 859 ± 231, p < 0.001 respectively). Conclusion: A higher VI indicates a higher i-PTH, and the VI may be a reliable predictor of the completeness of PEIT.
Evaluation of Operative Risk in Elderly Patients Undergoing Aortic Valve Replacement: The Predictive Value of Operative Risk Scores
Authors: Frilling Birgit , von Renteln-Kruse Wolfgang , Rieβ Friedrich-Christian
Published: August 2010

Objectives: An increasing number of elderly patients develop aortic valve disease requiring surgery. Operative risk scores are currently used to identify patients at high operative risk who may benefit from interventional treatment options. The aim of this study was to analyze the predictive value of these risk scores in geriatric patients undergoing aortic valve replacement. Methods: We reviewed data of 1,245 elderly patients who underwent aortic valve replacement with or without additional bypass surgery from 2000–2007. Patient data were derived from a prospective registry at the Department of Cardiac Surgery at Albertinen-Hospital in Hamburg, Germany. Results: Hospital mortality was 2.56% in isolated valve replacement and 3.38% in patients who had additional bypass surgery (p = ns). Age >80 years (OR 1.7; 95% CI: 1.3–3.3) and renal failure (OR 1.6; 95% CI: 1.1–2.5) were significantly associated with in-hospital death. All scores overestimated operative mortality. The median logistic EuroSCORE was 11.56% (interquartile range: 7.01–18.96), median STS score 13.9% (10.3–16.2); and median Ambler score 7.2% (4.1–9.3). There was a significant correlation of the STS score with operative mortality (Spearman’s rank coefficient: 0.68), but not with EuroSCORE (Spearman’s rank coefficient: 0.11) or Ambler score (Spearman’s rank coefficient: –0.17). Conclusion: Current risk scores overestimate operative risk in geriatric patients undergoing aortic valve replacement substantially. Of the risk scores evaluated, only STS score correlated significantly with operative mortality. Operative risk scores aimed specifically at geriatric patients may be necessary to accurately identify patients at high operative risk who benefit from non-surgical treatment options.
Differential Expression of Renal Proteins in a Rodent Model of Meckel Syndrome
Authors: Mason Stephen B. , Lai Xianyin , Ringham Heather N. , Bacallao Robert L. , Harris Peter C. , Witzmann Frank A. , Gattone, II Vincent H.
Published: August 2010

Background: Meckel syndrome (MKS) is a fatal autosomal recessive condition with prominent renal cystic pathology. Renal protein misexpression was evaluated in the Wpk rat model of human MKS3 gene disease to identify biomarkers for the staging of renal cystic progression. Methods: Misexpressed proteins were compared between early and late stages of MKS renal cystic disease using proteomic analysis (two-dimensional gel electrophoresis with LC-MS/MS identification) followed by Western blot analysis. Results: A proteomic analysis identified 76 proteins with statistically different, normalized abundance in at least one group. Subsequently, Western blot was used to confirm differential expression in several of these and polycystic kidney disease (PKD)-associated proteins. Galectin-1 and vimentin were identified as overexpressed proteins, which have been previously found in the jck mouse model of nephronophthisis 9. Ciliopathic PKD proteins, polycystins 1 & 2, and fibrocystin were also differentially expressed in Wpk kidney. Conclusion: In the Wpk rat, misexpressed proteins were identified that were also implicated in other forms of cystic disease. Numerous proteins were either over- or underexpressed in late-stage disease. Differences in protein expression may serve as biomarkers of cystic disease and its progression.
Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species
Authors: Cranenburg Ellen , Koos Ralf , Schurgers Leon , Magdeleyns Elke , Schoonbrood Thea , Landewé Robert , Brandenburg Vincent , Bekers Otto , Vermeer Cees
Published: August 2010

Matrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.
High platelet turnover and reactivity in renal transplant recipients patients
Authors: Marcucci Rossella , Gori Anna Maria , Caporale Roberto , Fanelli Alessandra , Paniccia Rita , Zanazzi Maria , Bertoni Elisabetta , Larti Aida , Salvadori Maurizio , Gensini Gian Franco , Abbate Rosanna , Cesari Francesca
Published: August 2010

Renal transplant recipients (RTRs) patients are at increased risk of cardiovascular morbidity and mortality. We aimed this study to assess reticulated platelets (RP), platelet reactivity and von Willebrand factor (vWF) levels in RTRs patients. In 150 RTRs patients [84 (56%) not on acetylsalicylic acid (ASA) treatment, group A; 66 (44%) on ASA 100 mg treatment, group B] and in 60 healthy control subjects, RP were measured by a Sysmex XE-2100 and were expressed as the percentage of RP of the total optical platelet count (immature platelet fraction; IPF), as the percentage of RP highly fluorescent (H-IPF) and as the absolute number of RP (IPF#). Platelet function was assessed by optical aggregometry (PA) induced by 1 mmol arachidonic acid (AA-PA), 2 and 10 μM ADP (ADP2-PA and ADP10-PA) and 2 μg/ml collagen (Coll-PA). vWF levels were measured by using a miniVidas analyser. Group A and group B showed significant higher values of RP than controls. At a multiple linear regression analysis IPF and IPF# were significantly and positively related to collagen-PA. By analysing group B according to residual platelet reactivity (RPR), we observed a significant higher number of RP among patients with RPR by collagen. Moreover at a multiple logistic regression analysis, IPF# significantly affected the risk of having a RPR by collagen. With regard to vWF, RTRs patients showed higher levels than control subjects. We documented a higher platelet turn-over in both groups of RTRs patients and increased platelet reactivity in RTRs patients not on ASA therapy than controls.
The role of CD154 in haematopoietic development
Authors: Seijkens Tom , Engel David , Tjwa Marc , Lutgens Esther
Published: August 2010

CD154 (CD40 ligand, CD40L, gp139) is a co-stimulatory molecule of the tumour necrosis factor (TNF) family. CD154 was originally discovered on T-cells, and was found to be involved in many immune responses including B-cell activation, isotype switching, and germinal centre formation. The expression of CD154 on other haematopoietic and nonhaematopoietic cells suggests that CD154 has other functions as well. Indeed, CD154 is involved in many pathological processes, including inflammatory and autoimmune diseases. Genetic studies in patients and mice taught us that CD154 might affect haematopoietic stem and progenitor cells (HSPCs), T-cell, B-cell, and dendritic cell (DC) progenitors. Moreover, the development of specific T-cell and DC subsets critically depends on CD154. Furthermore, CD154 is involved in lymphoid malignancies. Here we highlight the role of CD154 in the developing lymphoid system, including the biology of HSPC and lineage-committed T-cell, B-cell, NK, and DC progenitors. Further, the clinical and therapeutic implications of CD154 interactions in lymphopoiesis will be discussed.
Pioglitazone Suppresses Inflammation In Vivo in Murine Carotid Atherosclerosis
Authors: Chang Kiyuk , Francis Sanjeev A. , Aikawa Elena , Figueiredo Jose-Luiz , Kohler Rainer H. , McCarthy Jason R. , Weissleder Ralph , Plutzky Jorge , Jaffer Farouc A.
Published: August 2010

Objective—

To investigate the effects of pioglitazone (PIO), a peroxisome proliferator–activated receptor γ agonist, on plaque matrix metalloproteinase (MMP) and macrophage (Mac) responses in vivo in a molecular imaging study.

Methods and Results—

In vitro, PIO suppressed MMP-9 protein expression in murine peritoneal Macs (
P
<0.05). To assess PIO’s effects on plaque inflammation, nondiabetic apolipoprotein E
−/−
mice receiving a high-cholesterol diet (HCD) were administered an MMP-activatable fluorescence imaging agent and a spectrally distinct Mac-avid fluorescent nanoparticle. After 24 hours, mice underwent survival dual-target intravital fluorescence microscopy of carotid arterial plaques. These mice were then randomized to HCD or HCD plus 0.012% PIO for 8 weeks, followed by a second intravital fluorescence microscopy study of the same carotid plaque. In the HCD group, in vivo MMP and Mac target-to-background ratios increased similarly (
P
<0.01 versus baseline). In contrast, PIO reduced MMP and Mac target-to-background ratios (
P
<0.01) versus HCD. Changes in MMP and Mac signals correlated strongly (
r
≥0.75). Microscopy demonstrated MMP and Mac reductions in PIO-treated mice and a PIO-modulated increase in plaque collagen.

Conclusion—

Serial optical molecular imaging demonstrates that plaque MMP and Mac activity in vivo intensify with hypercholesterolemia and are reduced by PIO therapy.
Aging Induces Endothelial Dysfunction While Sparing Arterial Thrombosis
Authors: Stämpfli Simon F. , Akhmedov Alexander , Gebhard Cathérine , Lohmann Christine , Holy Erik W. , Rozenberg Izabela , Spescha Remo , Shi Yi , Lüscher Thomas F. , Tanner Felix C. , Camici Giovanni G.
Published: August 2010

Objective—

To assess the effects of aging on arterial thrombus formation by comparing 2-year-old with 11-week-old C57Bl6 mice.

Methods and Results—

Aging is a major risk factor for cardiovascular disease. In humans, assessing the direct effects of aging on vascular homeostasis is difficult because it occurs in the presence of other risk factors. Arterial thrombosis is the critical event in cardiovascular diseases; however, it is not known whether aging per se promotes its occurrence. Mice represent an interesting system to address this issue because they age without spontaneously developing other risk factors. Organ chamber experiments confirmed the advanced level of aging of old mice. As previously shown, old mice exhibited endothelial dysfunction; however, arterial thrombosis induced by photochemical injury was unchanged. Arterial tissue factor expression and activity; expressions of tissue factor pathway inhibitor, thrombomodulin, and plasminogen activator inhibitor 1; prothrombin time; partial thromboplastin time; thrombin-antithrombin complex; and platelet activation were comparable in both groups.

Conclusion—

Although these results cannot be directly extrapolated to humans, this study contributes novel important information on the direct effect of aging on arterial thrombosis and underscores the importance of controlling modifiable risk factors in aged individuals.
Inhibition of p38 Mitogen-Activated Protein Kinase Reduces Inflammation After Coronary Vascular Injury in Humans
Authors: Sarov-Blat Lea , Morgan John M. , Fernandez Pedro , James Rachel , Fang Zixing , Hurle Mark R. , Baidoo Charlotte , Willette Robert N. , Lepore John J. , Jensen Svend E. , Sprecher Dennis L.
Published: August 2010

Objective—To evaluate whether a p38α/β mitogen-activated protein kinase inhibitor, SB-681323, would limit the elevation of an inflammatory marker, high-sensitivity C-reactive protein (hsCRP), after a percutaneous coronary intervention (PCI).

Methods and Results—Coronary artery stents provide benefit by maintaining lumen patency but may incur vascular trauma and inflammation, leading to myocardial damage. A key mediator for such stress signaling is p38 mitogen-activated protein kinase. Patients with angiographically documented coronary artery disease receiving stable statin therapy and about to undergo PCI were randomly selected to receive SB-681323, 7.5 mg (n=46), or placebo (n=46) daily for 28 days, starting 3 days before PCI. On day 3, before PCI, hsCRP was decreased in the SB-681323 group relative to the placebo group (29% lower;P=0.02). After PCI, there was a statistically significant attenuation in the increase in hsCRP in the SB-681323 group relative to the placebo group (37% lower on day 5 [P=0.04]; and 40% lower on day 28 [P=0.003]). There were no adverse safety signals after 28 days of treatment with SB-681323.

Conclusion—In the setting of statin therapy, SB-681323 significantly attenuated the post-PCI inflammatory response, as measured by hsCRP. This inflammatory dampening implicates p38 mitogen-activated protein kinase in the poststent response, potentially defining an avenue to limit poststent restenosis.
Cardiac Small Conductance Ca
2+
-Activated K
+
Channel Subunits Form Heteromultimers via the Coiled-Coil Domains in the C Termini of the Channels
Authors: Tuteja Dipika , Rafizadeh Sassan , Timofeyev Valeriy , Wang Shuyun , Zhang Zheng , Li Ning , Mateo Robertino K. , Singapuri Anil , Young J. Nilas , Knowlton Anne A. , Chiamvimonvat Nipavan
Published: August 2010

Rationale:

Ca
2+
-activated K
+
channels are present in a wide variety of cells. We have previously reported the presence of small conductance Ca
2+
-activated K
+
(SK or K
Ca
) channels in human and mouse cardiac myocytes that contribute functionally toward the shape and duration of cardiac action potentials. Three isoforms of SK channel subunits (SK1, SK2, and SK3) are found to be expressed. Moreover, there is differential expression with more abundant SK channels in the atria and pacemaking tissues compared with the ventricles. SK channels are proposed to be assembled as tetramers similar to other K
+
channels, but the molecular determinants driving their subunit interaction and assembly are not defined in cardiac tissues.

Objective:

To investigate the heteromultimeric formation and the domain necessary for the assembly of 3 SK channel subunits (SK1, SK2, and SK3) into complexes in human and mouse hearts.

Methods and Results:

Here, we provide evidence to support the formation of heteromultimeric complexes among different SK channel subunits in native cardiac tissues. SK1, SK2, and SK3 subunits contain coiled-coil domains (CCDs) in the C termini. In vitro interaction assay supports the direct interaction between CCDs of the channel subunits. Moreover, specific inhibitory peptides derived from CCDs block the Ca
2+
-activated K
+
current in atrial myocytes, which is important for cardiac repolarization.

Conclusions:

The data provide evidence for the formation of heteromultimeric complexes among different SK channel subunits in atrial myocytes. Because SK channels are predominantly expressed in atrial myocytes, specific ligands of the different isoforms of SK channel subunits may offer a unique therapeutic opportunity to directly modify atrial cells without interfering with ventricular myocytes.
Notch3 Is Critical for Proper Angiogenesis and Mural Cell Investment
Authors: Liu Hua , Zhang Wenbo , Kennard Simone , Caldwell Ruth B. , Lilly Brenda
Published: August 2010

Rationale:

The heterotypic interactions of endothelial cells and mural cells (smooth muscle cells or pericytes) are crucial for assembly, maturation, and subsequent function of blood vessels. Yet, the molecular mechanisms underlying their association have not been fully defined.

Objective:

Our previous in vitro studies indicated that Notch3, which is expressed in mural cells, mediates these cell–cell interactions. To assess the significance of Notch3 on blood vessel formation in vivo, we investigated its role in retinal angiogenesis.

Methods and Results:

We show that Notch3-deficient mice exhibit reduced retinal vascularization, with diminished sprouting and vascular branching. Moreover, Notch3 deletion impairs mural cell investment, resulting in progressive loss of vessel coverage. In an oxygen-induced retinopathy model, we demonstrate that Notch3 is induced in hypoxia and interestingly, pathological neovascularization is decreased in retinas of Notch3-null mice. Analysis of oxygen-induced retinopathy mediators revealed that angiopoietin-2 expression is significantly reduced in the absence of Notch3. Furthermore, in vitro experiments showed that Notch3 is sufficient for angiopoietin-2 induction, and this expression is additionally enhanced in the presence of hypoxia-inducible factor 1α.

Conclusions:

These results provide compelling evidence that Notch3 is important for the investment of mural cells and is a critical regulator of developmental and pathological blood vessel formation.
Receptor-Independent Cardiac Protein Kinase Cα Activation by Calpain-Mediated Truncation of Regulatory Domains
Authors: Kang Min-Young , Zhang Yan , Matkovich Scot J. , Diwan Abhinav , Chishti Athar H. , Dorn Gerald W.
Published: August 2010

Rationale:

Protein kinase (PK)Cs and calpain cysteine proteases are highly expressed in myocardium. Ischemia produces calcium overload that activates calpains and conventional PKCs. However, calpains can proteolytically process PKCs, and the potential in vivo consequences of this interaction are unknown.

Objective:

To determine the biochemical and pathophysiological consequences of calpain-mediated cardiac PKCα proteolysis.

Methods and Results:

Isolated mouse hearts subjected to global ischemia/reperfusion demonstrated cleavage of PKCα. Calpain 1 overexpression was not sufficient to produce PKCα cleavage in normal hearts, but ischemia-induced myocardial PKCα cleavage and myocardial injury were greatly increased by cardiac-specific expression of calpain 1. In contrast, calpain 1 gene ablation or inhibition with calpastatin prevented ischemia/reperfusion induced PKCα cleavage; infarct size was decreased and ventricular function enhanced in infarcted calpain 1 knockout hearts. To determine consequences of PKCα fragmentation on myocardial protein phosphorylation, transgenic mice were created conditionally expressing full-length PKCα or its N-terminal and C-terminal calpain 1 cleavage fragments. Two-dimensional mapping of ventricular protein extracts showed a distinct PKCα phosphorylation profile that was exaggerated and distorted in hearts expressing the PKCα C-terminal fragment. MALDI mass spectroscopy revealed hyperphosphorylation of myosin-binding protein C and phosphorylation of atypical substrates by the PKCα C-terminal fragment. Expression of parent PKCα produced a mild cardiomyopathy, whereas myocardial expression of the C-terminal PKCα fragment induced a disproportionately severe, rapidly lethal cardiomyopathy.

Conclusions:

Proteolytic processing of PKCα by calcium-activated calpain activates pathological cardiac signaling through generation of an unregulated and/or mistargeted kinase. Production of the PKCα C-terminal fragment in ischemic hearts occurs via a receptor-independent mechanism.
Diagnostic Threshold Values of Cerebral Perfusion Measured With Computed Tomography for Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
Authors: Dankbaar Jan Willem , de Rooij Nicolien Karen , Rijsdijk Mienke , Velthuis Birgitta K. , Frijns Catharine J.M. , Rinkel Gabriel J.E. , van der Schaaf Irene C.
Published: August 2010

Background and Purpose—

Early diagnosis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage is critical but difficult. We analyzed diagnostic threshold values of CT perfusion for use in detection of DCI in patients with subarachnoid hemorrhage.

Methods—

We prospectively enrolled patients with subarachnoid hemorrhage with CT perfusion on admission and at time of clinical deterioration or after 1 week if no deterioration occurred. The gold standard was the clinical diagnosis of DCI based on all clinical, laboratory, and imaging data except CT perfusion. Patients with failed imaging (n=6) and other causes of deterioration (n=45) were excluded for the current study. We measured CT perfusion values, including cerebral blood volume, blood flow, mean transit time (MTT), and time to peak in predefined regions of interest and then compared absolute perfusion and perfusion asymmetry for patients with and without DCI. Diagnostic threshold values for DCI were evaluated and sensitivity and specificity calculated for optimal thresholds.

Results—

Of 85 eligible patients with subarachnoid hemorrhage, 50 had DCI; 35 patients with no clinical deterioration comprised the reference group. Cerebral blood flow was significantly lower, MTT higher, and perfusion asymmetry larger in patients with DCI. We found that largest absolute MTT and the MTT difference between hemispheres were good diagnostic tests. Diagnostic threshold values with optimal sensitivity and specificity were an MTT of 5.9 seconds and an MTT difference of 1.1 second.

Conclusion—

Thresholds for absolute MTT values and between-hemisphere MTT differences on CT perfusion can distinguish between patients with delayed cerebral ischemia and clinically stable patients.
MRI Markers of Small Vessel Disease in Lobar and Deep Hemispheric Intracerebral Hemorrhage
Authors: Smith Eric E. , Nandigam Kaveer R.N. , Chen Yu-Wei , Jeng Jed , Salat David , Halpin Amy , Frosch Matthew , Wendell Lauren , Fazen Louis , Rosand Jonathan , Viswanathan Anand , Greenberg Steven M.
Published: August 2010

Background and Purpose—

MRI evidence of small vessel disease is common in intracerebral hemorrhage (ICH). We hypothesized that ICH caused by cerebral amyloid angiopathy (CAA) or hypertensive vasculopathy would have different distributions of MRI T2 white matter hyperintensity (WMH) and microbleeds.

Methods—

Data were analyzed from 133 consecutive patients with primary supratentorial ICH and adequate MRI sequences. CAA was diagnosed using the Boston criteria. WMH segmentation was performed using a validated semiautomated method. WMH and microbleeds were compared according to site of symptomatic hematoma origin (lobar versus deep) or by pattern of hemorrhages, including both hematomas and microbleeds, on MRI gradient recalled echo sequence (grouped as lobar only–probable CAA, lobar only–possible CAA, deep hemispheric only, or mixed lobar and deep hemorrhages).

Results—

Patients with lobar and deep hemispheric hematoma had similar median normalized WMH volumes (19.5 cm versus 19.9 cm
3
,
P
=0.74) and prevalence of ≥1 microbleed (54% versus 52%,
P
=0.99). The supratentorial WMH distribution was similar according to hemorrhage location category; however, the prevalence of brain stem T2 hyperintensity was lower in lobar hematoma versus deep hematoma (54% versus 70%,
P
=0.004). Mixed ICH was common (23%). Patients with mixed ICH had large normalized WMH volumes and a posterior distribution of cortical hemorrhages similar to that seen in CAA.

Conclusions—

WMH distribution is largely similar between CAA-related and non-CAA-related ICH. Mixed lobar and deep hemorrhages are seen on MRI gradient recalled echo sequence in up to one fourth of patients; in these patients, both hypertension and CAA may be contributing to the burden of WMH.
Associations Between Peripheral Artery Disease and Ischemic Stroke
Authors: Banerjee Amitava , Fowkes F. Gerald , Rothwell Peter M.
Published: August 2010

Background and Purpose—

Although peripheral artery disease (PAD) has a particularly poor prognosis compared with vascular disease in other territories, little attention is paid to its epidemiology, treatment, and prevention. Despite the high prevalence of PAD in patients with stroke, and of stroke in patients with PAD, PAD is omitted from all guidelines for treatment, prevention, and rehabilitation of stroke, although coronary artery disease risk is considered. Therefore, routine PAD screening is seldom undertaken and so disease is probably often missed.

Summary of Review—

This review evaluates epidemiology of PAD in patients with stroke and of stroke in patients with PAD. The role of the ankle–brachial pressure index; imaging and novel markers in risk prediction of PAD in patients with stroke; and treatment and prevention of PAD are reviewed.

Conclusions—

In both primary and secondary prevention settings, PAD indicates a high risk of future events. Data on which additional preventive measures are beneficial in this patient group are lacking, but the presence of PAD does have implications for current management in both primary and secondary prevention of stroke.
Reoxygenation Attenuates the Adhesion of Neutrophils to Microvascular Endothelial Cells
Authors: Schmitz Katrin , Jennewein Martina , Pohlemann Tim , Seekamp Andreas , Oberringer Martin
Published: August 2010

In humans, the pathophysiological inflammation response subsequent to hypoxia and reoxygenation often leads to systemic inflammation and multiorgan failure. We applied a newly developed static interaction model using human polymorphonuclear neutrophils and microvasular endothelial cells to clarify the role of hypoxia and hypoxia/reoxygenation in vitro. Human dermal microvasular endothelial cell cultures (n = 7) were exposed to hypoxia and different reoxygenation periods and the adherence rate of neutrophils to the endothelial cells as well as to the protein matrix on the culture slide surface were determined by quantitative microscopy. Hypoxia clearly triggered neutrophil adhesion to human dermal microvasular endothelial cells whereas additional reoxygenation significantly decreased neutrophil adhesion. These in vitro findings suggest that systemic inflammation caused by increased neutrophil adherence to the microvascular endothelium is already initiated by hypoxia rather than by subsequent reoxygenation.
Exploding Cities: Housing the Masses in Paris, Chicago, and Mexico City, 1850—2000
Authors: Platt Harold L.
Published: August 2010

In The Mystery of Capitalism , the darling of neoliberalism, Hernando de Soto posits that secure property titles explain “why capitalism triumphs in the West and fails everywhere else.” While social scientists have taken him to task for an oversimplification of the causes and remedies of poverty, historians have contributed little to this important policy debate. Applying comparative methods across time and space, such a retrospective analysis exposes serious flaws in de Soto’s thesis. Case studies of Paris, Chicago, and Mexico City covering successive, fifty-year periods support his contention that property law was the single most important factor in determining the fate of rural migrants trying to find a place to live in these exploding cities. But in each case, residential property played a far more complex role in creating the social and physical geography of the city than its simple exchange value. This article illuminates some of these alternative economic uses and embedded cultural meanings of identities of place. It also shows how urban growth machines create capital value in property for some by creating environmental injustice of substandard conditions of everyday life for others.
Alternate Site Testing for Hemoglobin A1C in Children With Diabetes
Authors: Flores Sarah L.
Published: August 2010

Purpose

Alternate site testing is appropriate for blood glucose monitoring in euglycemic states, but use of alternate sites for collection of hemoglobin A1C has not been studied. The purpose of this study was to determine whether A1C results obtained from palm or forearm samples are equivalent to A1C results obtained from fingertip samples in a pediatric population. The secondary purposes were to determine whether there were differences in the perceived level of site pain and if there was a site preference.

Methods

Eighty-four children aged 5 to 20 years with type 1 or type 2 diabetes were randomly assigned to either fingertip and palm (N = 41) or fingertip and forearm (N = 40) groups. A1C samples were obtained in random order with 1 sample immediately following the other.

Results

Intraclass correlation coefficients were 0.99 for fingertip and palm, and 0.98 for fingertip and forearm. Paired t tests showed no differences between either set of values. Bland-Altman bias was minimal: -0.01% (95% confidence interval [CI], -0.07% to 0.05%) for the fingertip/ palm comparison and 0.0% (95% CI, -0.001 to 0.001) for the fingertip/forearm comparison. The fingertip was preferred by 54.8%, the forearm by 25%, and the palm by 20.2% of the children. Pain ratings were lowest for the forearm followed by the fingertip and palm.

Conclusions

Blood samples for measurement of A1C are clinically equivalent from the fingertip and palm or fingertip and forearm. Perceived pain was lowest when samples were obtained from the forearm. Just over half (54.8%) of the children preferred the fingertip.
The Cost of Self-Protection: Threat Response and Performance as a Function of Autonomous and Controlled Motivations
Authors: Hodgins Holley S. , Weibust Kristin S. , Weinstein Netta , Shiffman Sara , Miller Anita , Coombs Garth , Adair Kathryn C.
Published: August 2010

Seventy-seven undergraduates, primed for autonomous or controlled motivation, were videotaped and physiologically monitored during a stressful interview and subsequent speech. Interview videotapes were coded for behavioral measures of threat response; speech videotapes were coded for performance. It was hypothesized that relative to controlled motivation, autonomous motivation would decrease interview threat response and enhance speech performance, and that threat response would mediate the effect of motivation on performance. Results support the prediction across measures of verbal, paralinguistic, smiling, vocal fundamental frequency, and cardiovascular response. Autonomously primed participants continued to show less cardiovascular threat throughout the later speech and gave better speeches. Finally, speech performance was mediated by interview threat response. Results demonstrate that relative to controlled motivation, autonomous motivation lowers threat response, which enhances performance.
Being “In” With the In-Crowd: The Effects of Social Exclusion and Inclusion Are Enhanced by the Perceived Essentialism of Ingroups and Outgroups
Authors: Bernstein Michael J. , Sacco Donald F. , Young Steven G. , Hugenberg Kurt , Cook Eric
Published: August 2010

Social belonging is an essential human need. Belonging to social groups serves an important role in shaping our social identities. Nonetheless, research indicates that exclusion by ingroup and outgroup members seems equally aversive. The current studies test the hypothesis that unlike more trivial groups (e.g., smoking or computer preferences), highly essentialized groups may lead to differential effects of ingroup versus outgroup rejection. Consistent with this, exclusion and inclusion by racial ingroup members (relative to racial outgroup members) exacerbated the sting of rejection and the glow of inclusion (Study 1). In a second study, direct manipulations of essentialist beliefs about ingroups and outgroups (i.e., political affiliations) led to the same results. These results offer a novel demonstration that essentialized ingroup—outgroup distinctions enhance the sting of social exclusion and the positivity of social inclusion.
Ingroup Glorification, Moral Disengagement, and Justice in the Context of Collective Violence
Authors: Leidner Bernhard , Castano Emanuele , Zaiser Erica , Giner-Sorolla Roger
Published: August 2010

What aspects of ingroup identification can lead people to resist justice for the victims of their ingroup’s mistreatment? In three studies carried out in the United States and United Kingdom, in which participants read reports of mistreatment of prisoners and civilians by coalition troops in the Iraq war, ingroup glorification, but not ingroup attachment or other individual-difference variables, was a key predictor of lesser demands for justice, but only when the perpetrators belonged to the ingroup. This effect of glorification was mediated by two moral disengagement mechanisms focusing on the outgroup: minimization of the emotional suffering of the victims’ families and explicit dehumanization of the victim group. These findings further reinforce the difference between glorification and other forms of ingroup identification, demonstrating that glorification is problematic in maintaining and fostering intergroup relations because of its connection to moral disengagement.
Nurses’ Perceptions of the Organizational Supports Needed for the Delivery of Culturally Competent Care
Authors: Taylor Rosemarie Angela , Alfred Mary V.
Published: August 2010

The purpose of this study was to determine nurses’ views on the organizational supports needed for the delivery of culturally competent care. The research design was qualitative, with a case study approach. Data collection included face-to-face interviews with 23 registered nurses, document analysis, and reports of critical incidents. The findings of this study revealed that caring for culturally diverse clients was challenging and frustrating for most participants. Major themes emerging from the data included language barriers, lack of training, difficulty with cultural differences, lack of organizational support, and reliance on culturally diverse staff members. Few organizational supports existed for delivering culturally competent care. Expectations were not explicit, and culturally competent care was not rewarded or supported. Recommendations for organizations, nursing practice, theory, and future research are made.
Moderating Effect of Nurses’ Customer-Oriented Perception Between Organizational Citizenship Behaviors and Satisfaction
Authors: Chang Ching Sheng , Chang Hae Ching
Published: August 2010

This study investigates whether organizational citizenship behaviors enhance job satisfaction among nursing personnel, while exploring whether customer-oriented perception has a moderating effect between nursing personnel’s organizational citizenship behaviors and job satisfaction.The authors used a cross-sectional survey sent to 500 nurses with 232 valid responses. According to the research findings, nurses’ organizational citizenship behaviors have a positive and significant influence on job satisfaction. Results also indicated that the moderating effect of nurses’ customer-oriented perception on the relationship between their organizational citizenship behaviors and job satisfaction was stronger for high customer-oriented perception than it was low customer-oriented perception.
Goals of Fecal Incontinence Management Identified by Community-Living Incontinent Adults
Authors: Manthey Amanda , Bliss Donna Z. , Savik Kay , Lowry Ann , Whitebird Robin
Published: August 2010

The purpose of this study was to identify goals of fecal incontinence (FI) management and their importance to community-living adults if complete continence would not be possible. Participants expressed their goals of FI management in a semistructured interview, selected others from 12 investigator-identified goals, and rated their importance. Five thematic categories emerged from the 114 participant-identified goal statements: Fecal Incontinence/Bowel Pattern, Lifestyle, Emotional Responses, Adverse Effects of Fecal Incontinence, and Self-Care Practices. Participants selected a median of seven investigator-identified goals (range = 2 to 12). Goals selected by the most participants were decreased number of leaks of stool and greater confidence in controlling fecal incontinence. These goals also had the highest importance along with decreased leakage of loose or liquid stool. The type and number of management goals identified by participants offer a toolbox of options from which to focus therapy when cure is not possible and promote patient satisfaction.