bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Legged Hop Tests as Predictors of Self-Reported Knee Function in Nonoperatively Treated Individuals With Anterior Cruciate Ligament Injury
Authors: Grindem Hege , Logerstedt David , Eitzen Ingrid , Moksnes Håvard , Axe Michael J. , Snyder-Mackler Lynn , Engebretsen Lars , Risberg May Arna 
Published: August 2011

Background: Previous studies have found significant predictors for functional outcome after anterior cruciate ligament (ACL) reconstruction; however, studies examining predictors for functional outcome in nonoperatively treated individuals are lacking. Hypothesis: Single-legged hop tests predict self-reported knee function (International Knee Documentation Committee [IKDC] 2000) in nonoperatively treated ACL-injured individuals 1 year after baseline testing. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: Ninety-one nonoperatively treated patients with an ACL injury were tested using 4 single-legged hop tests on average 74 ± 30 days after injury in a prospective cohort study. Eighty-one patients (89%) completed the IKDC 2000 1 year later. Patients with an IKDC 2000 score equal to or higher than the age- and gender-specific 15th percentile score from previously published data on an uninjured population were classified as having self-reported function within normal ranges. Logistic regression analyses were performed to identify predictors of self-reported knee function. The area under the curve (AUC) from receiver operating characteristic curves was used as a measure of discriminative accuracy. Optimal limb symmetry index (LSI) cutoff for the best single-legged hop test was defined as the LSI with the highest product of sensitivity and specificity. Results: Single hop for distance symmetry indexes predicted self-reported knee function at the 1-year follow-up ( P = .036). Combinations of any 2 hop tests (AUC = 0.64-0.71) did not give a higher discriminative accuracy than the single hop alone (AUC = 0.71). A cutoff of 88% (LSI) for the single hop revealed a sensitivity of 71.4% and a specificity of 71.7%. Conclusion: The single hop for distance (LSI) significantly predicted self-reported knee function after 1 year in nonoperatively treated ACL-injured patients. Combinations of 2 single-legged hop tests did not lead to higher discriminative accuracy than the single hop alone.
Factor XIIa regulates the structure of the fibrin clot independently of thrombin generation through direct interaction with fibrin
Authors: Konings Joke , Govers-Riemslag José W. P. , Philippou Helen , Mutch Nicola J. , Borissoff Julian I. , Allan Peter , Mohan Sumitra , Tans Guido , ten Cate Hugo , Ariëns Robert A. S. 
Published: August 2011

AbstractRecent data indicate an important contribution of coagulation factor (F)XII to in vivo thrombus formation. Because fibrin structure plays a key role in clot stability and thrombosis, we hypothesized that FXII(a) interacts with fibrin(ogen) and thereby regulates clot structure and function. In plasma and purified system, we observed a dose-dependent increase in fibrin fiber density and decrease in turbidity, reflecting a denser structure, and a nonlinear increase in clot stiffness with FXIIa. In plasma, this increase was partly independent of thrombin generation, as shown in clots made in prothrombin-deficient plasma initiated with snake venom enzyme and in clots made from plasma deficient in FXII and prothrombin. Purified FXII and α-FXIIa, but not β-FXIIa, bound to purified fibrinogen and fibrin with nanomolar affinity. Immunostaining of human carotid artery thrombi showed that FXII colocalized with areas of dense fibrin deposition, providing evidence for the in vivo modulation of fibrin structure by FXIIa. These data demonstrate that FXIIa modulates fibrin clot structure independently of thrombin generation through direct binding of the N-terminus of FXIIa to fibrin(ogen). Modification of fibrin structure by FXIIa represents a novel physiologic role for the contact pathway that may contribute to the pathophysiology of thrombosis.
Role of ZBP-89 in human globin gene regulation and erythroid differentiation
Authors: Woo Andrew J. , Kim Jonghwan , Xu Jian , Huang Hui , Cantor Alan B. 
Published: August 2011

Abstract
The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf, and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34+ cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral short hairpin RNAs knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the histone deacetylase inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation.
Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial
Authors: Braun Thorsten , Itzykson Raphael , Renneville Aline , de Renzis Benoit , Dreyfus François , Laribi Kamel , Bouabdallah Krimo , Vey Norbert , Toma Andrea , Recher Christian , Royer Bruno , Joly Bertrand , Vekhoff Anne , Lafon Ingrid , Sanhes Laurence , Meurice Guillaume , Oréar Cédric , Preudhomme Claude , Gardin Claude , Ades Lionel , Fontenay Michaela , Fenaux Pierre , Droin Nathalie , Solary Eric ,   on behalf of the Groupe Francophone des Myélodysplasies
Published: August 2011

AbstractHydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With a median follow-up of 23 months, overall survival was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and janus kinase 2 (JAK2) genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1γ, did not predict response or survival on DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in approximately 40% of CMML patients with advanced myeloproliferative or myelodysplastic features and suggested that CJUN and CMYB expression could be potential biomarkers in this setting. This trial is registered at EudraCT (eudract.ema.europa.eu) as #2008-000470-21 and www.clinicaltrials.gov as #NCT01098084.
DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation
Authors: Shaknovich Rita , Cerchietti Leandro , Tsikitas Lucas , Kormaksson Matthias , De Subhajyoti , Figueroa Maria E. , Ballon Gianna , Yang Shao Ning , Weinhold Nils , Reimers Mark , Clozel Thomas , Luttrop Karin , Ekstrom Tomas J. , Frank Jared , Vasanthakumar Aparna , Godley Lucy A. , Michor Franziska , Elemento Olivier , Melnick Ari 
Published: August 2011

Abstract
The phenotype of germinal center (GC) B cells includes the unique ability to tolerate rapid proliferation and the mutagenic actions of activation induced cytosine deaminase (AICDA). Given the importance of epigenetic patterning in determining cellular phenotypes, we examined DNA methylation and the role of DNA methyltransferases in the formation of GCs. DNA methylation profiling revealed a marked shift in DNA methylation patterning in GC B cells versus resting/naive B cells. This shift included significant differential methylation of 235 genes, with concordant inverse changes in gene expression affecting most notably genes of the NFkB and MAP kinase signaling pathways. GC B cells were predominantly hypomethylated compared with naive B cells and AICDA binding sites were highly overrepresented among hypomethylated loci. GC B cells also exhibited greater DNA methylation heterogeneity than naive B cells. Among DNA methyltransferases (DNMTs), only DNMT1 was significantly up-regulated in GC B cells. Dnmt1 hypomorphic mice displayed deficient GC formation and treatment of mice with the DNA methyltransferase inhibitor decitabine resulted in failure to form GCs after immune stimulation. Notably, the GC B cells of Dnmt1 hypomorphic animals showed evidence of increased DNA damage, suggesting dual roles for DNMT1 in DNA methylation and double strand DNA break repair.
Bone marrow–derived CMPs and GMPs represent highly functional proangiogenic cells: implications for ischemic cardiovascular disease
Authors: Wara Akm Khyrul , Croce Kevin , Foo ShiYin , Sun Xinghui , Icli Basak , Tesmenitsky Yevgenia , Esen Fehim , Rosenzweig Anthony , Feinberg Mark W. 
Published: August 2011

Abstract
Clinical studies using bone marrow–derived proangiogenic cells (PACs) have demonstrated modest improvements of function and/or perfusion of ischemic myocardium or skeletal muscle. Because the identities of these PACs and their functional ability to promote neovascularization remain poorly understood, it is possible that a subset of robust PACs exists but is obscured by the heterogeneous nature of this cell population. Herein, we found that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) preferentially differentiate into PACs compared with megakaryocyte-erythrocyte progenitors, hematopoietic stem cells, and common lymphoid progenitors. In vivo hindlimb ischemia studies and Matrigel plug assays verified the enhanced neovascularization properties uniquely associated with PACs derived from CMPs and GMPs. Taken together, these observations identify CMPs and GMPs as key bone marrow progenitors for optimal PAC function in vitro and in vivo and provide a foundation for novel therapeutic approaches to modulate angiogenesis.
Prognostic factors related to sequelae in childhood bacterial meningitis: Data from a Greek meningitis registry
Authors: Vasilopoulou Vasiliki A , Karanika Maria , Theodoridou Kalliopi , Katsioulis Antonios T , Theodoridou Maria N , Hadjichristodoulou Christos S 
Published: August 2011

AbstractBackgroundBacterial meningitis (BM) is a life-threatening disease, often related with serious complications and sequelae. Infants and children who survive bacterial meningitis often suffer neurological and other sequelae.MethodsA total of 2,477 patients aged 1 month to 14 years old hospitalized in a Children's Hospital in Greece diagnosed with acute bacterial meningitis were collected through a Meningitis Registry, from 1974 to 2005. Clinical, laboratory and other parameters (sex, age, pathogen, duration of symptoms before and after admission) were evaluated through univariate and multivariate analysis with regard to sequelae. Analysis of acute complications were also studied but not included in the final model.ResultsThe rate of acute complications (arthritis and/or subdural effusion) was estimated at 6.8% (152 out of 2,251 patients, 95%CI 5.8-7.9) while the rate of sequelae (severe hearing loss, ventriculitis, hydrocephalus or seizure disorder) among survivors was estimated at 3.3% (73 out of 2,207 patients, 95%CI 2.6-4.2). Risk factors on admission associated with sequelae included seizures, absence of hemorrhagic rash, low CSF glucose, high CSF protein and the etiology of meningitis. A combination of significant prognostic factors including presence of seizures, low CSF glucose, high CSF protein, positive blood culture and absence of petechiae on admission presented an absolute risk of sequelae of 41.7% (95%CI 15.2-72.3).ConclusionsA combination of prognostic factors of sequelae in childhood BM may be of value in selecting patients for more intensive therapy and in identifying possible candidates for new treatment strategies.
Non-pharmacological treatment of hypertension in primary health care: A comparative clinical trial of two education strategies in health and nutrition
Authors: Ribeiro Amanda G , Ribeiro Sônia MR , Dias Cristina MGC , Ribeiro Andréia Q , Castro Fátima AF , Suárez-Varela Maria M , Cotta Rosângela MM 
Published: August 2011

AbstractBackgroundPoor adherence to non-pharmacological treatment of hypertension represents a serious challenge for public health policies in several countries. This study was conducted to compare two intervention strategies regarding the adherence of adult women to dietary changes recommended for the treatment of hypertension in a community covered by Primary Health Care Unit.MethodsThis study is a randomized controlled trial of a sample composed of 28 women with hypertension enrolled in the Primary Health Care Unit located in the urban area of southeastern Brazil. The participants were already undergoing treatment for hypertension but devoid of nutritional care; and were divided into two groups, each composed of 14 individuals, who received interventions that consisted of two different strategies of nutritional guidance: monthly health education workshops alone (Group 1) and combined with family orientation through home visits (Group 2). Adherence to nutritional guidelines was evaluated by dietary, anthropometric, clinical and serum biochemical parameters, measured before and after the interventions. Knowledge on control and risk of hypertension was also investigated. The study lasted five months.ResultsMean age was 55.6 (± 2.8) and 50.7 (± 6.5) in the groups 1 and 2, respectively. The home orientation strategy promoted greater adherence to dietary changes, leading to a statistically significant improvement in the clinical, anthropometric, biochemical and dietary parameters. The group 2 reduced the consumption of risk foods (p = 0.01), oil (p = 0.002) and sugar (p = 0.02), and decreased body mass index (-0.7 kg/m2; p = 0.01); waist circumference (-4.2 cm; p = 0.001), systolic blood pressure (-13 mm HG; p = 0.004) and glycemia (-18.9 mg/dl; p = 0. 01). In group 1 only waist circumference (-2 cm; p = 0.01) changed significantly.ConclusionNutritional orientations at the household level were more effective with regard to the adherence of individuals to non-pharmacological treatment of hypertension, regarding the reduction of clinical and behavioral risk parameters.
Effectiveness of interventions to improve the health and housing status of homeless people: a rapid systematic review
Authors: Fitzpatrick-Lewis Donna , Ganann Rebecca , Krishnaratne Shari , Ciliska Donna , Kouyoumdjian Fiona , Hwang Stephen W 
Published: August 2011

AbstractBackgroundResearch on interventions to positively impact health and housing status of people who are homeless has received substantially increased attention over the past 5 years. This rapid review examines recent evidence regarding interventions that have been shown to improve the health of homeless people, with particular focus on the effect of these interventions on housing status.MethodsA total of 1,546 articles were identified by a structured search of five electronic databases, a hand search of grey literature and relevant journals, and contact with experts. Two reviewers independently screened the first 10% of titles and abstracts for relevance. Inter-rater reliability was high and as a result only one reviewer screened the remaining titles and abstracts. Articles were included if they were published between January 2004 and December 2009 and examined the effectiveness of an intervention to improve the health or healthcare utilization of people who were homeless, marginally housed, or at risk of homelessness. Two reviewers independently scored all relevant articles for quality.ResultsEighty-four relevant studies were identified; none were of strong quality while ten were rated of moderate quality. For homeless people with mental illness, provision of housing upon hospital discharge was effective in improving sustained housing. For homeless people with substance abuse issues or concurrent disorders, provision of housing was associated with decreased substance use, relapses from periods of substance abstinence, and health services utilization, and increased housing tenure. Abstinent dependent housing was more effective in supporting housing status, substance abstinence, and improved psychiatric outcomes than non-abstinence dependent housing or no housing. Provision of housing also improved health outcomes among homeless populations with HIV. Health promotion programs can decrease risk behaviours among homeless populations.ConclusionsThese studies provide important new evidence regarding interventions to improve health, housing status, and access to healthcare for homeless populations. The additional studies included in this current review provide further support for earlier evidence which found that coordinated treatment programs for homeless persons with concurrent mental illness and substance misuse issues usually result in better health and access to healthcare than usual care. This review also provides a synthesis of existing evidence regarding interventions that specifically support homeless populations with HIV.
Aspirin-triggered lipoxin A4attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells
Authors: Wang Yan-Ping , Wu Yan , Li Long-Yan , Zheng Jin , Liu Ren-Gang , Zhou Jie-Ping , Yuan Shi-Ying , Shang You , Yao Shang-Long 
Published: August 2011

Abstract

Background
Microglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (NO) and several pro-inflammatory cytokines. Lipoxins (LXs) and aspirin-triggered LXs (ATLs) are considered to act as 'braking signals' in inflammation. In the present study, we investigated the effect of aspirin-triggered LXA4 (ATL) on infiammatory responses induced by lipopolysaccharide (LPS) in murine microglial BV-2 cells.

Methods
BV-2 cells were treated with ATL prior to LPS exposure, and the effects of such treatment production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were analysed by Griess reaction, ELISA, western blotting and quantitative RT-PCR. Moreover, we investigated the effects of ATL on LPS-induced nuclear factor-κB (NF-κB) activation, phosphorylation of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) activation.

Results
ATL inhibited LPS-induced production of NO, IL-1β and TNF-α in a concentration-dependent manner. mRNA expressions for iNOS, IL-1β and TNF-α in response to LPS were also decreased by ATL. These effects were inhibited by Boc-2 (a LXA4 receptor antagonist). ATL significantly reduced nuclear translocation of NF-κB p65, degradation of the inhibitor IκB-α, and phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK in BV-2 cells activated with LPS. Furthermore, the DNA binding activity of NF-κB and AP-1 was blocked by ATL.

Conclusions
This study indicates that ATL inhibits NO and pro-inflammatory cytokine production at least in part via NF-κB, ERK, p38 MAPK and AP-1 signaling pathways in LPS-activated microglia. Therefore, ATL may have therapeutic potential for various neurodegenerative diseases.
IPNV with high and low virulence: host immune responses and viral mutations during infection
Authors: Skjesol Astrid , Skjæveland Ingrid , Elnæs Marianne , Timmerhaus Gerrit , Fredriksen Børge N , Jørgensen Sven Martin , Krasnov Aleksei , Jørgensen Jorunn B 
Published: August 2011

AbstractBackgroundInfectious pancreatic necrosis virus (IPNV) is an aquatic member of theBirnaviridaefamily that causes widespread disease in salmonids. IPNV is represented by multiple strains with markedly different virulence. Comparison of isolates reveals hyper variable regions (HVR), which are presumably associated with pathogenicity. However little is known about the rates and modes of sequence divergence and molecular mechanisms that determine virulence. Also how the host response may influence IPNV virulence is poorly described.MethodsIn this study we compared two field isolates of IPNV (NFH-Ar and NFH-El). The sequence changes, replication and mortality were assessed following experimental challenge of Atlantic salmon. Gene expression analyses with qPCR and microarray were applied to examine the immune responses in head kidney.ResultsSignificant differences in mortality were observed between the two isolates, and viral load in the pancreas at 13 days post infection (d p.i.) was more than 4 orders of magnitude greater for NFH-Ar in comparison with NFH-El. Sequence comparison of five viral genes from the IPNV isolates revealed different mutation rates and Ka/Ks ratios. A strong tendency towards non-synonymous mutations was found in the HRV of VP2 and in VP3. All mutations in VP5 produced precocious stop codons. Prior to the challenge, NFH-Ar and NFH-El possessed high and low virulence motifs in VP2, respectively. Nucleotide substitutions were noticed already during passage of viruses in CHSE-214 cells and their accumulation continued in the challenged fish. The sequence changes were notably directed towards low virulence. Co-ordinated activation of anti-viral genes with diverse functions (IFN-a1 and c, sensors - Rig-I, MDA-5, TLR8 and 9, signal transducers - Srk2, MyD88, effectors - Mx, galectin 9, galectin binding protein, antigen presentation - b2-microglobulin) was observed at 13 d p.i. (NFH-Ar) and 29 d p.i. (both isolates).ConclusionsMortality and expression levels of the immune genes were directly related to the rate of viral replication, which was in turn associated with sequences of viral genes. Rapid changes in the viral genome that dramatically reduced virus proliferation might indicate a higher susceptibility to protective mechanism employed by the host. Disease outbreak and mortality depend on a delicate balance between host defence, regulation of signalling cascades and virus genomic properties.