bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and Long-Term Follow-Up of Silent Cerebral Lesions After Pulmonary Vein Isolation Using a Remote Robotic Navigation System as Compared With Manual Ablation
Authors: Rillig Andreas , Meyerfeldt Udo , Tilz Roland Richard , Talazko Jochen , Arya Anita , Zvereva Vlada , Birkemeyer Ralf , Miljak Tomislav , Hajredini Bajram , Wohlmuth Peter , Fink Ulrich , Jung Werner 
Published: January 2012

Background—
The incidence of silent cerebral lesions (SCL) after atrial fibrillation (AF) ablation is highly variable, depending on the technology used. Recently, an increased risk for SCL has been described for a novel, nonirrigated ablation tool using multielectrode phased radiofrequency (PVAC). The aim of this prospective study was to evaluate the incidence and long-term follow-up of SCL in patients undergoing robotically assisted pulmonary vein isolation (RA-PVI) as compared with manual PVI.

Methods and Results—
Circumferential PVI using irrigated radiofrequency current was performed on 70 patients (41 patients with paroxysmal AF, 59%). Fifty patients underwent RA-PVI and 20 patients underwent a manual approach. Cerebral MRI was performed the day before and the day after the ablation procedure; follow-up MRI was performed on 9 of 12 (75%) patients after a follow-up period of 21 months. SCLs were found in 12 of 70 (17%) patients in this study; the incidence of SCLs was similar in patients undergoing RA-PVI as compared with manually ablated patients (n=9, 18% versus n=3, 15%; probability value=1.0). In 1 patient undergoing manual PVI (1%), an SCL with asymptomatic subarachnoid hemorrhage was detected; the bleeding completely resolved within 1 month. Transient ischemic attack occurred in 1 (1%) patient 2 days after manual PVI. After a median follow-up period of 21 months, no residual SCLs were detected.

Conclusions—
The incidence of SCL using the robotic navigation system was 18% in this study. Incidence and size of SCL appears to be similar after RA-PVI as compared with manual PVI. Repeat MRI showed no residual SCLs at long-term follow-up.
A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I
Authors: Makita Naomasa , Seki Akiko , Sumitomo Naokata , Chkourko Halina , Fukuhara Shigetomo , Watanabe Hiroshi , Shimizu Wataru , Bezzina Connie R. , Hasdemir Can , Mugishima Hideo , Makiyama Takeru , Baruteau Alban , Baron Estelle , Horie Minoru , Hagiwara Nobuhisa , Wilde Arthur A.M. , Probst Vincent , Le Marec Hervé , Roden Dan M. , Mochizuki Naoki , Schott Jean-Jacques , Delmar Mario 
Published: January 2012

Background—

Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as
SCN5A
that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation.

Methods and Results—

We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line
GJA5
(connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT], 22.2±1.7 nS, n=14; Cx40-Q58L, 0.56±0.34 nS, n=14;
P
<0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ≈50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques.

Conclusions—
Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system.
Acculturation and Outcomes Among Patients With Heart Failure
Authors: Peterson Pamela N. , Campagna Elizabeth J. , Maravi Moises , Allen Larry A. , Bull Sheana , Steiner John F. , Havranek Edward P. , Dickinson L. Miriam , Masoudi Frederick A. 
Published: January 2012

Background—
Acculturation to US society among minority patients may—beyond race and ethnicity alone—influence health outcomes beyond race and ethnicity alone. In particular, those who are foreign-born and who do not speak English as their primary language may have greater challenges interacting with the health care system and thus be at greater risk for adverse outcomes.

Methods and Results—
We studied patients hospitalized with a principal discharge diagnosis of heart failure between January 2000 and December 2007 in an integrated delivery system that cares for minority patients. Individuals were defined as having low acculturation if their primary language was not English and their country of birth was outside of the United States. Multivariable logistic regression and Cox proportional hazards regression were used to determine the independent risk of 30-day rehospitalization and 1-year mortality, respectively. Candidate adjustment variables included demographics (age, sex, race/ethnicity), coexisting illnesses, laboratory values, left ventricular systolic function, and characteristics of the index admission. Of 1268 patients, 30% (n=379) were black, 39% (n=498) were Hispanic, and 27% (n=348) were white. Eighteen percent (n=228) had low acculturation. After adjustment, low acculturation was associated with a higher risk of readmission at 30 days (odds ratio, 1.70; 95% confidence interval, 1.07–2.68) but not 1-year all-cause mortality (hazard ratio, 0.69; 95% confidence interval, 0.42–1.14).

Conclusions—
Patients with heart failure who are foreign-born and do not speak English as their primary language have a greater risk of rehospitalization, independent of clinical factors and race/ethnicity. Future studies should evaluate whether culturally concordant interventions focusing on such patients may improve outcomes for this patient population.
Decline in Heart Transplant Wait List Mortality in the United States Following Broader Regional Sharing of Donor Hearts
Authors: Singh Tajinder P. , Almond Christopher S. , Taylor David O. , Graham Dionne A. 
Published: January 2012

Background—
A change in allocation algorithm in July 2006 allowed broader regional sharing of donor hearts in the United States (US). We assessed if the allocation change has been associated with a decline in wait list mortality in the US.

Methods and Results—

We compared baseline characteristics and outcomes in patients ≥18 years old listed for a primary heart transplant in the US before (July 1, 2004–July 11, 2006, Era1) and after (July 12, 2006–June 30, 2009, Era 2) the change in allocation algorithm. Of 11 864 patients in the study, 4503 were listed during Era 1 and 7361 during Era 2. Patients listed during Era 2 were more likely to be listed status 1A, have an implantable cardioverter-defibrillator, and supported on a continuous flow assist device (
P
<0.001 for distribution. Patients listed in Era 2 were at a 17% lower risk of dying on the wait list or becoming too sick to transplant (adjusted hazard ratio, 0.83, 95% CI 0.75, 0.93). Transplant recipients in Era 2 were more likely to be transplanted as status 1A (37% versus 48%, respectively,
P
<0.001). Post-transplant in-hospital mortality (6.3% versus 5.4%; adjusted odds ratio, 0.86 for Era 2, 95% CI 0.79, 1.06) and 1-year survival were similar.

Conclusions—
The risk of death on the wait list or becoming too sick to transplant has decreased by 17% in the US since the allocation algorithm allowing broader regional sharing was implemented in 2006. The shift in hearts to sicker candidates has not resulted in higher in-hospital or first year post-transplant mortality.
Gremlin Plays a Key Role in the Pathogenesis of Pulmonary Hypertension
Authors: Cahill Edwina , Costello Christine M. , Rowan Simon C. , Harkin Susan , Howell Katherine , Leonard Martin O. , Southwood Mark , Cummins Eoin P. , Fitzpatrick Susan F. , Taylor Cormac T. , Morrell Nicholas W. , Martin Finian , McLoughlin Paul 
Published: January 2012

Background—
Pulmonary hypertension occurs in chronic hypoxic lung diseases, significantly worsening morbidity and mortality. The important role of altered bone morphogenetic protein (BMP) signaling in pulmonary hypertension was first suspected after the identification of heterozygous BMP receptor mutations as the underlying defect in the rare heritable form of pulmonary arterial hypertension. Subsequently, it was demonstrated that BMP signaling was also reduced in common forms of pulmonary hypertension, including hypoxic pulmonary hypertension; however, the mechanism of this reduction has not previously been elucidated.

Methods and Results—
Expression of 2 BMP antagonists, gremlin 1 and gremlin 2, was higher in the lung than in other organs, and gremlin 1 was further increased in the walls of small intrapulmonary vessels of mice during the development of hypoxic pulmonary hypertension. Hypoxia stimulated gremlin secretion from human pulmonary microvascular endothelial cells in vitro, which inhibited endothelial BMP signaling and BMP-stimulated endothelial repair. Haplodeficiency of gremlin 1 augmented BMP signaling in the hypoxic mouse lung and reduced pulmonary vascular resistance by attenuating vascular remodeling. Furthermore, gremlin was increased in the walls of small intrapulmonary vessels in idiopathic pulmonary arterial hypertension and the rare heritable form of pulmonary arterial hypertension in a distribution suggesting endothelial localization.

Conclusions—
These findings demonstrate a central role for increased gremlin in hypoxia-induced pulmonary vascular remodeling and the increased pulmonary vascular resistance in hypoxic pulmonary hypertension. High levels of basal gremlin expression in the lung may account for the unique vulnerability of the pulmonary circulation to heterozygous mutations of BMP type 2 receptor in pulmonary arterial hypertension.
Consequences of subacute intratracheal exposure of rats to cadmium oxide nanoparticles
Authors: Papp András , Oszlánczi Gábor , Horváth Edina , Paulik Edit , Kozma Gábor , Sápi András , Kónya Zoltán , Szabó Andrea 
Published: January 2012

Cadmium (Cd) is a metal used in various industrial applications, thereby causing exposure to Cd-containing fumes. The submicron-sized particles in the fumes represent an extra risk due to their high mobility within the organism and high surface area. Toxicity of Cd on the liver, kidney and bones is well known, but there are less data on its neurotoxicity. Here, male Wistar rats were treated for 3 and 6 weeks by intratracheal instillation of cadmium oxide nanosuspension. The body weight gain in treated rats was significantly decreased, and in the rats treated with high dose (0.4 mg/kg Cd daily), there was a significant increase in the weight of lungs and thymus. In this group, the spectrum of spontaneous cortical electrical activity was shifted to higher frequencies, the latency of sensory-evoked potentials was lengthened, and the frequency following ability of the somatosensory evoked potential was impaired—even without detectable Cd deposition in the brain. The data support the role of the nano-sized Cd in the causation of nervous system damage and show the possibility of modeling human neurotoxic damage in rats.
Nephron-specific expression of components of the renin–angiotensin–aldosterone system in the mouse kidney
Authors: Reinhold Stephan W , Krüger Bernd , Barner Caroline , Zoicas Flavius , Kammerl Martin C , Hoffmann Ute , Bergler Tobias , Banas Bernhard , Krämer Bernhard K 
Published: January 2012

Introduction: The renin–angiotensin–aldosterone system (RAAS) plays an integral role in the regulation of blood pressure, electrolyte and fluid homeostasis in mammals. The capability of the different nephron segments to form components of the RAAS is only partially known. This study therefore aimed to characterize the nephron-specific expression of RAAS components within the mouse kidney. Materials and methods: Defined nephron segments of adult C57B/16 mice were microdissected after collagenase digestion. The gene expression of renin, angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II receptors 1a (AT1a), 1b (AT1b), and 2 (AT2) was assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Results: Renin mRNA was present in glomeruli, in proximal tubules, in distal convoluted tubules (DCT) and cortical collecting ducts (CCD). AGT mRNA was found in proximal tubules, descending thin limb of Henle’s loop (dTL) and in the medullary part of the thick ascending limb (mTAL). ACE mRNA was not detectable in microdissected mouse nephron segments. AT1a, AT1b and AT2 mRNA was detected in glomeruli and proximal convoluted tubules. Conclusions: Our data demonstrate a nephron-specific distribution of RAAS components. All components of the local RAAS – except ACE – are present in proximal convoluted tubules, emphasizing their involvement in sodium and water handling.
Contributions of an artistic educational program for older people with early dementia: An exploratory qualitative study
Authors: Ullán Ana M. , Belver Manuel H. , Badía Marta , Moreno Carmen , Garrido Eugenio , Gómez-Isla José , Gonzalez-Ingelmo Elena , Delgado Juan , Serrano Isabel , Herrero Carmen , Manzanera Paloma , Tejedor Laura 
Published: January 2012

Objective: To describe a contemporary artistic educational program based on photographic cyanotype techniques and to present the results of the program carried out with older people with early dementia. We determined whether these people could participate in the program, their viewpoint about it, and what this program could contribute to their experience. Method: Twenty-one people diagnosed with mild or moderate dementia participated in a series of artistic education workshops. While conducting the workshops, participant observation was carried out, and the participants’ engagement was assessed. Upon completing the series, five focus groups were held with the participants with dementia, and another focus group with their professional caretakers. Results: We observed the participants’ high level of commitment to the activity and their interest in learning new things. We also observed the participants’ satisfaction during the creative process and with their results. The artistic activities not only reinforced the feelings of capacity of the participants with early dementia but also transmitted a positive image of them. Conclusions: Dementia was not an obstacle to participation in the program, which was an opportunity for creativity, learning, enjoyment, and communication for people with dementia. In the authors’ opinion, facilitating access to art and artistic education to people with early dementia can contribute to enforcing their rights and to improving the care system.
Photography in social work research: Using visual image to humanize findings
Authors: Russell Amy Catherine , Diaz Natalie D. 
Published: January 2012

The purpose of this article is to present the use of photography as a supplement to a classic grounded theory research study with lesbian women regarding their experience of identity, culture, and oppression. Photography was integrated into the grounded theory methodology to visually express the theoretical codes that emerged from the grounded theory of liberated identity. Photographs are presented with coded substages and participant in vivo codes, including explanations of the visual representation in the photographs. The findings, the basic social process substage photographs, were guided by the participants to best convey visual meaning of their experience. The photographic images reveal how the use of photography, in concert with Glaserian grounded theory, exemplified experience, humanity, and meaning in this specific research study, and thus the complementary visual image can edify the significance in the humanness and affectivity of research participants.
Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function
Authors: Tai Yu-Tzu , Horton Holly M. , Kong Sun-Young , Pong Erik , Chen Hsing , Cemerski Saso , Bernett Matthew J. , Nguyen Duc-Hanh T. , Karki Sher , Chu Seung Y. , Lazar Greg A. , Munshi Nikhil C. , Desjarlais John R. , Anderson Kenneth C. , Muchhal Umesh S. 
Published: January 2012

AbstractHM1.24, an immunologic target for multiple myeloma (MM) cells, has not been effectively targeted with therapeutic monoclonal antibodies (mAbs). In this study, we investigated in vitro and in vivo anti-MM activities of XmAb5592, a humanized anti-HM1.24 mAb with Fc-domain engineered to significantly enhance FcγR binding and associated immune effector functions. XmAb5592 increased antibody-dependent cellular cytotoxicity (ADCC) several fold relative to the anti-HM1.24 IgG1 analog against both MM cell lines and primary patient myeloma cells. XmAb5592 also augmented antibody dependent cellular phagocytosis (ADCP) by macrophages. Natural killer (NK) cells became more activated by XmAb5592 than the IgG1 analog, evidenced by increased cell surface expression of granzyme B–dependent CD107a and MM cell lysis, even in the presence of bone marrow stromal cells. XmAb5592 potently inhibited tumor growth in mice bearing human MM xenografts via FcγR-dependent mechanisms, and was significantly more effective than the IgG1 analog. Lenalidomide synergistically enhanced in vitro ADCC against MM cells and in vivo tumor inhibition induced by XmAb5592. A single dose of 20 mg/kg XmAb5592 effectively depleted both blood and bone marrow plasma cells in cynomolgus monkeys. These results support clinical development of XmAb5592, both as a monotherapy and in combination with lenalidomide, to improve patient outcome of MM.
Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs
Authors: Dumont Jennifer A. , Liu Tongyao , Low Susan C. , Zhang Xin , Kamphaus George , Sakorafas Paul , Fraley Cara , Drager Douglas , Reidy Thomas , McCue Justin , Franck Helen W. G. , Merricks Elizabeth P. , Nichols Timothy C. , Bitonti Alan J. , Pierce Glenn F. , Jiang Haiyan 
Published: January 2012

Abstract
Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation.
A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function
Authors: Roumenina Lubka T. , Frimat Marie , Miller Elizabeth C. , Provot Francois , Dragon-Durey Marie-Agnes , Bordereau Pauline , Bigot Sylvain , Hue Christophe , Satchell Simon C. , Mathieson Peter W. , Mousson Christiane , Noel Christian , Sautes-Fridman Catherine , Halbwachs-Mecarelli Lise , Atkinson John P. , Lionet Arnaud , Fremeaux-Bacchi Veronique 
Published: January 2012

Abstract
Atypical hemolytic uremic syndrome (aHUS) is a rare renal thrombotic microangiopathy commonly associated with rare genetic variants in complement system genes, unique to each patient/family. Here, we report 14 sporadic aHUS patients carrying the same mutation, R139W, in the complement C3 gene. The clinical presentation was with a rapid progression to end-stage renal disease (6 of 14) and an unusually high frequency of cardiac (8 of 14) and/or neurologic (5 of 14) events. Although resting glomerular endothelial cells (GEnCs) remained unaffected by R139W-C3 sera, the incubation of those sera with GEnC preactivated with pro-inflammatory stimuli led to increased C3 deposition, C5a release, and procoagulant tissue-factor expression. This functional consequence of R139W-C3 resulted from the formation of a hyperactive C3 convertase. Mutant C3 showed an increased affinity for factor B and a reduced binding to membrane cofactor protein (MCP; CD46), but a normal regulation by factor H (FH). In addition, the frequency of at-risk FH and MCP haplotypes was significantly higher in the R139W-aHUS patients, compared with normal donors or to healthy carriers. These genetic background differences could explain the R139W-aHUS incomplete penetrance. These results demonstrate that this C3 mutation, especially when associated with an at-risk FH and/or MCP haplotypes, becomes pathogenic following an inflammatory endothelium-damaging event.
How I treat heparin-induced thrombocytopenia
Authors: Cuker Adam , Cines Douglas B. 
Published: January 2012

Abstract
Heparin-induced thrombocytopenia is a prothrombotic adverse drug effect induced by platelet-activating antibodies against multimolecular complexes of platelet factor 4 and heparin. Diagnosis rests on a clinical assessment of disease probability and laboratory testing. Management involves immediate discontinuation of heparin and initiation of an alternative anticoagulant. Because of the frequency of thrombocytopenia among heparinized patients, the limited specificity of widely available immunoassays, the limited availability of more specific functional assays, and clinicians' fears of missing a case of true disease, overtesting, overdiagnosis, and overtreatment have become common. As a result, a substantial number of thrombocytopenic patients are unnecessarily exposed to costly alternative anticoagulants and their attendant risk of bleeding. In this review, we describe not only our approach to the evaluation and management of patients with heparin-induced thrombocytopenia, but also the measures we use to minimize misdiagnosis and unnecessary treatment of patients without the disease. In addition, we propose areas of investigation for improvement of the diagnosis and management of this potentially fatal disorder.