bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model of Polymicrobial Peritonitis That Induces the Proinflammatory and Immunosuppressive Phases of Sepsis
Authors: Barrera Gabriela , Landoni Verónica , Martire-Greco Daiana , Chiarella Paula , Meiss Roberto , Gómez Sonia A. , Alves-Rosa Fernanda , Rearte Barbara , Isturiz Martín , Palermo Marina S. , Fernández Gabriela C. 
Published: December 2010

ABSTRACTSevere sepsis is associated with early release of inflammatory mediators that contribute to the morbidity and mortality observed during the first stages of this syndrome. Although sepsis is a deadly, acute disease, high mortality rates have been observed in patients displaying evidence of sepsis-induced immune deactivation. Although the contribution of experimental models to the knowledge of pathophysiological and therapeutic aspects of human sepsis is undeniable, most of the current studies using animal models have focused on the acute, proinflammatory phase. We developed a murine model that reproduces the early acute phases but also the long-term consequences of human sepsis. We induced polymicrobial acute peritonitis (AP) by establishing a surgical connection between the cecum and the peritoneum, allowing the exit of intestinal bacteria. Using this model, we observed an acute phase with high mortality, leukopenia, increased interleukin-6 levels, bacteremia, and neutrophil activation. A peak of leukocytosis on day 9 or 10 revealed the persistence of the infection within the lung and liver, with inflammatory hepatic damage being shown by histological examination. Long-term (20 days) derangements in both innate and adaptive immune responses were found, as demonstrated by impaired systemic tumor necrosis factor alpha production in response to an inflammatory stimulus; a decreased primary humoral immune response and T cell proliferation, associated with an increased number of myeloid suppressor cells (Gr-1+CD11b+) in the spleen; and a low clearance capacity. This model provides a good approach to attempt novel therapeutic interventions directed to augmenting host immunity during late sepsis.
Leptospira santorosai
Serovar Shermani Detergent Extract Induces an Increase in Fibronectin Production through a Toll-Like Receptor 2-Mediated Pathway
Authors: Tian Ya-Chung , Hung Cheng-Chieh , Li Yi-Jung , Chen Yung-Chang , Chang Ming-Yang , Yen Tzung-Hai , Hsu Hsiang-Hao , Wu Mai-Szu , Phillips Aled , Yang Chih-Wei 
Published: December 2010

ABSTRACT

Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that
Leptospira santorosai
serovar Shermani detergent extract stimulates ECM accumulation
in vitro
. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-κB, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition.
The Use of Popular Fiction to Present a Professional Scientific Career to High School Students
Authors: Durand Caylib , Ramón-García Santiago 
Published: December 2010

In a previous Tips & Tools article, Patricia J. Baynham advocated for the introduction of science to students by hosting scientists in classrooms. We approached the issue from a different perspective. Since the ability of scientists to demonstrate science could be hampered with limited time and classroom resources, we proposed to introduce students to a professional and active scientific environment for a one-day outreach program. Our goal was to give students hands-on training, mentorship, career information, and an opportunity to ask questions to facilitate a possible career choice in research.
Briefly, the “CSI at the LSI” outreach program (LSI, Life Sciences Institute), based on the popular fiction “Crime Scene Investigation” (CSI) TV show, was a murder mystery involving a plot with real characters (grad students, postdocs, and professors) to generate a fun and interactive learning environment. The students carried out experiments using modern scientific techniques to collect “evidence.” At the end of the day, they share the results to identify the suspect.
The Sci-Fi Microbe: Reinforcing Understanding of Microbial Structures and their Significance Through a Creative Writing Exercise
Authors: Dolberry Adrienne A. 
Published: December 2010

By blending storytelling with topics in biology, a fun activity can be created for students to strengthen their scientific knowledge. The “Sci-Fi Microbe” writing assignment lets students create an altered version of a known microorganism, and write a story describing an unusual observation that leads the characters discovery of their new microorganism.
The Sci-Fi Microbe exercise is appropriate for any microbiology course where the instructor has previously reviewed structures, metabolism, and growth conditions of microorgan-isms. Since students are responsible for developing and writing their own stories, the activity allows for the instructor to assess students’ understanding in an exercise where they are required to articulate the connection of the microbe to its environment – thereby discouraging simple memorization of facts
Comparison study of growth plate fusion using MRI versus plain radiographs as used in age determination for exclusion of overaged football players
Authors: George John , Nagendran Jayaselvi , Azmi Khairul 
Published: December 2010

BackgroundMRI of distal radius fusion is currently being used in the U17 World Cup to exclude overaged players. Developing countries that cannot afford to perform MRI on their players are using plain radiographs based on the same MRI criteria of fusion.ObjectiveThe aim of this study is to compare the grade of fusion of the left wrist distal radial growth plate between MRI and plain radiographs.Methods150 healthy male football players were grouped into five age groups ranging from 15 to 19 years old. Each participant had coronal T1-weighted MRI and plain radiograph of the left wrist. The degree of distal radius fusion was rated randomly by three radiologists using a six-stage grading system proposed by the FIFA Research Centre.ResultsMRI assessment of distal radial growth plate fusion has good correlation with plain radiograph fusion (r=0.949). The mean of x-ray grading is higher than the MRI grading in the 15, 16, 17, 18 and 19 years old age groups with p=0.443, 0.001, 0.009, <0.001 and 0.003, respectively, using Wilcoxon signed ranked test. Intraobserver and interobserver correlations were high (r=0.9). T1 MRI correlation with chronological age (r=0.771) was close to plain radiographs (r=0.821) with p value of <0.001.ConclusionThis article is of major importance as it is the first to show that x-rays significantly overrate the grading of fusion in this age group and therefore should not be used to exclude overaged players as is occurring now to the distress of many genuinely eligible players.
MYCN Sensitizes Human Neuroblastoma to Apoptosis by HIPK2 Activation through a DNA Damage Response
Authors: Petroni Marialaura , Veschi Veronica , Prodosmo Andrea , Rinaldo Cinzia , Massimi Isabella , Carbonari Maurizio , Dominici Carlo , McDowell Heather P. , Rinaldi Christian , Screpanti Isabella , Frati Luigi , Bartolazzi Armando , Gulino Alberto , Soddu Silvia , Giannini Giuseppe 
Published: December 2010

Abstract
MYCN amplification occurs in approximately 20% of human neuroblastomas and is associated with early tumor progression and poor outcome, despite intensive multimodal treatment. However, MYCN overexpression also sensitizes neuroblastoma cells to apoptosis. Thus, uncovering the molecular mechanisms linking MYCN to apoptosis might contribute to designing more efficient therapies for MYCN-amplified tumors. Here we show that MYCN-dependent sensitization to apoptosis requires activation of p53 and its phosphorylation at serine 46. The p53S46 kinase HIPK2 accumulates on MYCN expression, and its depletion by RNA interference impairs p53S46 phosphorylation and apoptosis. Remarkably, MYCN induces a DNA damage response that accounts for the inhibition of HIPK2 degradation through an ATM- and NBS1-dependent pathway. Prompted by the rare occurrence of p53 mutations and by the broad expression of HIPK2 in our human neuroblastoma series, we evaluated the effects of the p53-reactivating compound Nutlin-3 on this pathway. At variance from other tumor histotypes, in MYCN-amplified neuroblastoma, Nutlin-3 further induced HIPK2 accumulation, p53S46 phosphorylation, and apoptosis, and in combination with clastogenic agents purged virtually the entire cell population. Altogether, our data uncover a novel mechanism linking MYCN to apoptosis that can be triggered by the p53-reactivating compound Nutlin-3, supporting its use in the most difficult-to-treat subset of neuroblastoma. Mol Cancer Res; 9(1); 67–77 ©2010 AACR.
A prospective study of an aggressive warfarin dosing algorithm to reach and maintain INR 2 to 3 after heart valve surgery
Authors: Kim Yang-Ki , Carter Donna , Schulman Sam , Meijer Karina 
Published: December 2010

SummaryGood anticoagulation control in patients during the first months after heart valve surgery is important to prevent thrombotic complications. This is difficult to achieve, partly because the sensitivity to warfarin decreases progressively during approximately three months after valve surgery. A recently developed, simple but aggressive algorithm might improve anticoagulation control in this patient group. It was the objective of this study to evaluate the level of anticoagulation control when a specialised anticoagulation clinic changed from empirical dosing to the use of this new algorithm. In a before-and-after design, a cohort of consecutive patients managed with a new, aggressive dosing algorithm (‘Algorithm cohort’) was compared to a ‘Retrospective cohort’ of similar patients dosed empirically. Primary endpoint was individual time in therapeutic range (ITTR) during the first three months of warfarin therapy. Secondary endpoints included proportion of extreme International Normalised Ratio (INR) results, thrombotic and bleeding complications. Ninety-eight patients were included in the Algorithm cohort, 94 of whom were warfarin-naïve. Two hundred patients were included in the Retrospective cohort. Mean ITTR was 60.1% in the Algorithm cohort versus 48.7% in the Retrospective cohort (p <0.001). Patients in the Algorithm cohort spent 0.5% of time at an INR >5, versus 0.2 % in the Retrospective cohort. There was no major bleeding in either cohort; one patient in each cohort had a thrombotic complication. We demonstrate an improvement of the level of anticoagulation control with the use of a condition-specific, aggressive algorithm, as compared to standard dosing, in patients after heart valve surgery.
High-shear- and-thrombin-inducible platelet adhesion and aggregation in patients undergoing percutaneous coronary intervention
Authors: Eslam Roza Badr , Reiter Nina , Kaider Alexandra , Lang Irene , Panzer Simon 
Published: December 2010

SummaryThrombin-generation and activation of platelets during percutaneous coronary intervention (PCI) play a key role for early thrombotic events. Heparin and bivalirudin are approved anticoagulants for PCI. We examined the specific effects of these anticoagulants on platelet adhesion and aggregation under high shear conditions, and the presence of excess thrombin. To simulate in vivo conditions that may precipitate a bleeding/thrombotic event, we added thrombin in vitro to blood samples from 89 stable patients who had been randomly assigned to receive heparin or bivalirudin for elective PCI and examined thrombininducible platelet adhesion and aggregation under high shear conditions. Platelet adhesion increased by 10% of baseline with heparin, but decreased by 20% with bivalirudin (p=0.0047). Thrombin-inducible platelet adhesion and size of aggregates was equally inhibited by heparin and bivalirudin. Thus, under high shear conditions and excessive thrombin generation as they occur in atherosclerotic vascular compartments and acute vascular syndromes, heparin and bivalirudin inhibit thrombin-induced platelet adhesion and aggregation to a similar extent, while they have opposite effects on platelet adhesion in the absence of thrombin.This study was part of the doctorial thesis of NR at the Department of Blood Group Serology and Transfusion Medicine.
The natural tissue plasminogen activator inhibitor neuroserpin and acute ischaemic stroke outcome
Authors: Sobrino Tomás , Miranda Elena , Brea David , Ossa Natalia Pérez de la , Blanco Miguel , Pérez Juan , Dorado Laura , Castellanos Mar , Lomas David , Moro Maria , Dávalos Antoni , Rodríguez-González Raquel , Millán Mónica , Castillo José 
Published: December 2010

SummaryNeuroserpin is a brain-derived natural inhibitor of tissue plasminogen activator (tPA) that has shown neuroprotective effects in animal models of brain ischaemia. Our aim was to investigate the association of neuroserpin levels in blood with functional outcome in patients with acute ischaemic stroke. Due to the potential effect of tPA treatment interfering on neuroserpin levels, we studied two different cohorts: 129 patients not treated with tPA and 80 patients treated with intravenous tPA within 3 hours (h) from symptoms onset. Neuroserpin levels were measured by ELISA. Good functional outcome at three months was defined as Rankin scale score ≤2. In the two cohorts, serum neuroserpin levels on admission were significantly higher than at 24 h, 72 h and in healthy subjects. In non tPA-treated patients, neuroserpin levels decrease at 24 h, but not levels at baseline, were associated with good outcome (for each quartile decrease, adjusted odds ratio [OR] 15.0; 95% confidence interval [CI], 3.5 to 66). In the tPA-treated cohort, high neuroserpin levels before tPA bolus had the stronger effect on favourable outcome (for each quartile, OR 13.5; 95%CI, 3.9 to 47). Furthermore, for each quartile in neuroserpin levels before tPA bolus there was a 80% (95%CI, 48 to 92) reduction in the probability of subsequent parenchymal haematoma. In summary, high serum neuroserpin levels before intravenous tPA and neuroserpin levels decrease at 24 h after ischaemic stroke, independently of tPA treatment, are associated with good functional outcome. These findings support the concept that neuroserpin might play an important role during cerebral ischaemia.
Autologous Cardiomyotissue Implantation Promotes Myocardial Regeneration, Decreases Infarct Size, and Improves Left Ventricular Function
Authors: Wykrzykowska Joanna J. , Rosinberg Audrey , Lee Seung U. , Voisine Pierre , Wu Guifu , Appelbaum Evan , Boodhwani Munir , Sellke Frank W. , Laham Roger J. 
Published: December 2010

Background—Cell therapy for myocardial infarction (MI) may be limited by poor cell survival and lack of transdifferentiation. We report a novel technique of implanting whole autologous myocardial tissue from preserved myocardial regions into infarcted regions.Methods and Results—Fourteen rats were used to optimize cardiomyotissue size with peritoneal wall implantation (300 μm identified as optimal size). Thirty-nine pigs were used to investigate cardiomyotissue implantation in MI induced by left anterior descending balloon occlusion (10 animals died; male-to-female transplantation for tracking with in situ hybridization for Y chromosome, n=4 [2 donors and 2 MI animals]; acute MI implantation cohort at 1 hour, n=13; and healed MI implantation at 2 weeks, n=12). Assessment included echocardiography, magnetic resonance imaging, hemodynamics, triphenyltetrazolium chloride staining, and histological and molecular analyses. Tracking studies demonstrated viable implants with donor cells interspersed in the adjacent myocardium with gap junctions and desmosomes. In the acute MI cohort, treated animals compared with controls had improved perfusion by magnetic resonance imaging (1.2±0.01 versus 0.86±0.05;P<0.01), decreased MI size (magnetic resonance imaging: left ventricle, 2.2±0.5% versus 5.4±1.5%,P=0.04; triphenyltetrazolium chloride: anterior wall, 10.3±4.6% versus 28.9±5.8%,P<0.03), and improved contractility (dP/dt, 1235±215 versus 817±817;P<0.05). In the healed MI cohort, treated animals had less decline in ejection fraction between 2 and 4 week assessment (−3±4% versus −13±−4%;P<0.05), less decline in ±dP/dt, and smaller MI (triphenyltetrazolium chloride, 21±11% versus 3±8%;P=0.006) than control animals. Infarcts in the treated animals contained more mdr-1+cells and fewer c-kit+cells with a trend for decreased expression of matrix metalloproteinase-2 and increased expression of tissue inhibitor of metalloproteinase-2.Conclusion—Autologous cardiomyotissue implanted in an MI area remains viable, exhibits electromechanical coupling, decreases infarct size, and improves left ventricular function.
Relative Merits of Left Ventricular Dyssynchrony, Left Ventricular Lead Position, and Myocardial Scar to Predict Long-Term Survival of Ischemic Heart Failure Patients Undergoing Cardiac Resynchronization Therapy
Authors: Delgado Victoria , van Bommel Rutger J. , Bertini Matteo , Borleffs C. Jan Willem , Marsan Nina Ajmone , Ng Arnold C.T. , Nucifora Gaetano , van de Veire Nico R.L. , Ypenburg Claudia , Boersma Eric , Holman Eduard R. , Schalij Martin J. , Bax Jeroen J. 
Published: December 2010

Background—
The relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome after cardiac resynchronization therapy remain unknown and were evaluated in the present study.

Methods and Results—

In 397 ischemic heart failure patients, 2-dimensional speckle tracking imaging was performed, with comprehensive assessment of LV radial dyssynchrony, identification of the segment with latest mechanical activation, and detection of myocardial scar in the segment where the LV lead was positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used. Segments with <16.5% radial strain in the region of the LV pacing lead were considered to have extensive myocardial scar (>50% transmurality, validated in a subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position was derived from chest x-ray. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was 133±98 milliseconds. In 271 patients (68%), the LV lead was placed at the latest activated segment (concordant LV lead position), and the mean value of peak radial strain at the targeted segment was 18.9±12.6%. Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995;
P
=0.001), whereas a discordant LV lead position (hazard ratio, 2.086;
P
=0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913;
P
<0.001) were independent predictors of worse outcome. Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters.

Conclusions—
Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in ischemic heart failure patients treated with cardiac resynchronization therapy. Larger baseline LV dyssynchrony predicted superior long-term survival, whereas discordant LV lead position and myocardial scar predicted worse outcome.
Trends in Out-of-Hospital Deaths Due to Coronary Heart Disease in Sweden (1991 to 2006)
Authors: Dudas Kerstin , Lappas Georg , Stewart Simon , Rosengren Annika 
Published: December 2010

Background—
Case fatality associated with a first coronary event is often underestimated when only those who survive to reach a hospital are considered. Few studies have examined long-term trends in case fatality associated with a major coronary event that occurs out of the hospital.

Methods and Results—
Record linkage documented all case subjects 35 to 84 years of age in Sweden during 1991 to 2006 with a first major coronary event (out-of-hospital coronary death or hospitalization for acute myocardial infarction). Of the 384 597 cases identified, 111 319 (28.9%) died out of the hospital, and another 36 552 (9.5%) died in the hospital or within 28 days of hospitalization. From 1991 to 2006, out-of hospital deaths as a proportion of all major coronary events declined from 30.5% to 25.6% (adjusted mean annual decrease 2.2%, 95% confidence interval 2.1% to 2.4%), however, with a larger decline in 28-day case fatality in hospitalized cases (adjusted mean annual decrease 5.8%, 95% confidence interval 5.5% to 6.0%). As a result of the faster decline in in-hospital deaths, the relative contribution of out-of-hospital deaths to overall case fatality increased, particularly among younger individuals (eg, among those 35 to 54 years of age, no more than 10.8% of all deaths occurred in hospitalized cases during 2003–2006). Although female sex (odds ratio 0.85, 95% confidence interval 0.83 to 0.87) and older age (odds ratio 0.972, 95% confidence interval 0.971 to 0.974 per year) were associated with lower risk for initial out-of-hospital death, each successive calendar year was associated with increased risk (odds ratio 1.041, 95% confidence interval 1.038 to 1.044).

Conclusions—
The great majority of all fatal coronary events occur outside the hospital, and this proportion is increasing, particularly among younger individuals.