bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of cytosolic phospholipase A2 alpha signalling pathway in spontaneous and transforming growth factor‐beta‐induced activation of rat hepatic stellate cells
Authors: Zhao Liena , Gandhi Chandrashekhar R. , Gao Zu‐hua 
Published: September 2011

AbstractBackgroundHepatic stellate cells (HSCs) are extracellular matrix‐producing cells that play a pivotal role in liver fibrogenesis. During liver injury and when cells are placed in vitro, HSCs undergo phenotypic transition from quiescent retinoid‐storing cells to activated retinoid‐deficient myofibroblast‐like cells. Although several mediators including reactive oxygen species, platelet derived growth factor, transforming growth factor‐beta (TGF‐β) and tumour necrosis factor‐alpha (TNF‐α) were implicated in HSC activation, the cellular signalling pathways that regulate this process remain incompletely defined.AimsThe objectives of this study were to evaluate the role of cytosolic phospholipase A2 alpha (cPLA2α) and peroxisome proliferator‐activated receptor‐beta/delta (PPAR‐β/δ) in HSC activation.MethodsRat HSCs were isolated, purified, cultured and stimulated with TGF‐β1 in the presence or absence of the selective cPLA2α inhibitor, arachidonyltrifluoromethyl ketone (AACOCF3). The activation status of HSC was evaluated by immunofluorescent staining of alpha‐smooth muscle actin (α‐SMA) and by measuring the expression of cPLA2α, cyclooxygenase 2 (COX‐2) and PPAR‐β/δ using western blot analysis.ResultsRapid and significant increase in cPLA2α expression was observed during activation of HSCs. These events preceded the elevation of PPAR‐β/δ and the expression of α‐SMA. Elevated expression of cPLA2α, but not COX‐2, was also observed during TGF‐β‐induced HSC activation. The TGF‐β‐induced α‐SMA expression was blocked by AACOCF3. Furthermore, transfection of a cPLA2α expression vector enhanced the transcription activity of PPAR‐β/δ and the expression of α‐SMA in HSCs.ConclusioncPLA2α‐mediated induction of PPAR‐β/δ is a novel intracellular signalling pathway in spontaneous and TGF‐β induced activation of HSCs and could be a potential therapeutic target for the treatment of liver fibrosis.
Meaningful Improvement in Gait Speed in Hip Fracture Recovery
Authors: Alley Dawn E. , Hicks Gregory E. , Shardell Michelle , Hawkes William , Miller Ram , Craik Rebecca L. , Mangione Kathleen K. , Orwig Denise , Hochberg Marc , Resnick Barbara , Magaziner Jay 
Published: September 2011

OBJECTIVES: To estimate meaningful improvements in gait speed observed during recovery from hip fracture and to evaluate the sensitivity and specificity of gait speed changes in detecting change in self‐reported mobility.
DESIGN: Secondary longitudinal data analysis from two randomized controlled trials
SETTING: Twelve hospitals in the Baltimore, Maryland, area.
PARTICIPANTS: Two hundred seventeen women admitted with hip fracture.
MEASUREMENTS: Usual gait speed and self‐reported mobility (ability to walk 1 block and climb 1 flight of stairs) measured 2 and 12 months after fracture.
RESULTS: Effect size–based estimates of meaningful differences were 0.03 for small differences and 0.09 for substantial differences. Depending on the anchor (stairs vs walking) and method (mean difference vs regression), anchor‐based estimates ranged from 0.10 to 0.17 m/s for small meaningful improvements and 0.17 to 0.26 m/s for substantial meaningful improvement. Optimal gait speed cutpoints yielded low sensitivity (0.39–0.62) and specificity (0.57–0.76) for improvements in self‐reported mobility.
CONCLUSION: Results from this sample of women recovering from hip fracture provide only limited support for the 0.10‐m/s cut point for substantial meaningful change previously identified in community‐dwelling older adults experiencing declines in walking abilities. Anchor‐based estimates and cut points derived from receiver operating characteristic curve analysis suggest that greater improvements in gait speed may be required for substantial perceived mobility improvement in female hip fracture patients. Furthermore, gait speed change performed poorly in discriminating change in self‐reported mobility. Estimates of meaningful change in gait speed may differ based on the direction of change (improvement vs decline) or between patient populations.
Cost‐Effectiveness of Oral Bisphosphonates for Osteoporosis at Different Ages and Levels of Life Expectancy
Authors: Pham Annalise N. , Datta Santanu K. , Weber Thomas J. , Walter Louise C. , Colón‐Emeric Cathleen S. 
Published: September 2011

OBJECTIVES: To evaluate the cost‐effectiveness of oral bisphosphonate therapy for osteoporosis in women at different ages and life expectancies.
DESIGN: A Markov model was used to analyze oral bisphosphonate treatment for 5 years compared to no intervention. Women at each age were divided into life expectancy quartiles: the lowest 1% to 25% (sickest group), the two middle 26% to 75% (average health group), and the highest 76% to 100% of life expectancy (healthiest group). Simulations were performed for hypothetical cohorts at 5‐year intervals with starting ages between 50 and 90 and for each life expectancy group and followed for up to 100 years or until death. Data sources included published fracture rates, costs, utility values, and mortality risks.
SETTING: Computer simulation using a societal perspective.
PARTICIPANTS: Hypothetical cohort of women with various life expectancies beginning osteoporosis treatment between the age of 50 and 90 years.
MEASUREMENTS: Cost per quality‐adjusted life years (QALY) gained for 5 years of bisphosphonate therapy compared to no treatment. Cost‐effectiveness was defined at a willingness‐to‐pay of $50,000.
RESULTS: In the healthiest group, all costs were less than $18,000 per QALY. In the median quartiles of life expectancy, lifetime costs per QALY were less than $27,000 for patients at all ages; treatment became cost‐saving at a starting age of 75 and remained so through a starting age of 85. Even in the sickest group, although osteoporosis treatment was not cost‐saving, it remained cost‐effective through a starting age of 90 with lifetime costs of less than $43,000 per QALY.
CONCLUSION: Treatment with an oral bisphosphonate for 5 years was cost‐effective for all women, regardless of quartile of life expectancy. Advanced age should not prevent consideration of osteoporosis treatment based on cost effectiveness, and strategies to improve care, such as nurse‐led screening programs or electronic medical record tools, are needed.
Implication of transfected cell lines for the detection of alloantibodies against human neutrophil antigen‐3
Authors: Bayat Behnaz , Tjahjono Yudy , Werth Silke , Berghöfer Heike , Reil Angelika , Kroll Hartmut , Sachs Ulrich J. , Santoso Sentot 
Published: September 2011

BACKGROUND: Alloantibodies against human neutrophil antigen‐3 (HNA‐3) are responsible for the fatalities reported in transfusion‐related acute lung injury. Consequently, reliable detection of these alloantibodies is mandatory to improve blood transfusion safety. In this study, we developed stable cell lines for the detection of HNA‐3 antibodies.STUDY DESIGN AND METHODS: HEK293T were transfected with HNA‐3a or HNA‐3b constructs and sorted by flow cytometry according to high surface expression. Transfected cells were tested with sera containing HNA‐3 antibodies in flow cytometry and antibody capture assay (ACA). The results were compared with granulocyte agglutination test and granulocyte immunofluorescence test.RESULTS: In flow cytometry, 12 of 14 HNA‐3a sera reacted specifically with HNA‐3aa cells. One serum sample showed positive reaction with HNA‐3bb cells. All HNA‐3b sera recognized HNA‐3bb cells. No reaction was observed with broad reactive antibodies against HLA Class I. In ACA, all HNA‐3a sera (12/12) showed positive reactivity with HNA‐3aa cells with no cross‐reactivity with HNA‐3bb cells. Again, all HNA‐3b sera reacted with HNA‐3bb cells only. Furthermore, genotyping of 249 individuals detected a new HNA‐3 allele caused by a nucleotide substitution C>T at Position 457 leading to L153F mutation in choline transporter‐like protein‐2. This mutation impairs polymerase chain reaction with sequence‐specific primers based HNA‐3a typing. However, analysis with cells expressing F153 isoform showed that this mutation did not alter the binding of HNA‐3 antibodies.CONCLUSIONS: This study demonstrated that HEK293T cells expressing stable recombinant HNA‐3 are suitable for the detection of HNA‐3 alloantibodies allowing reliable screening of blood products.
Long‐term follow‐up among Danish transfusion recipients identified in the national hepatitis C lookback
Authors: Just Søren Andreas , Grau Katrine , Georgsen Jørgen , Weis Nina , Cowan Susan , Groenbaek Karin , Krarup Henrik , Christensen Peer Brehm ,   The Danish HCV Lookback Group
Published: September 2011

BACKGROUND: In 1996, a national lookback study was performed in Denmark identifying 1018 patients exposed to hepatitis C virus (HCV) by transfusion before 1991. The objective of this study was to describe morbidity and mortality during extended follow‐up among patients in the Danish HCV lookback cohort alive in 1996.STUDY DESIGN AND METHODS: In a retrospective cohort study of 230 patients exposed to HCV by blood transfusion and alive in 1996 we extracted data from national registers and compared these with a matched group of unexposed transfusion recipients.RESULTS: Among 230 HCV‐exposed recipients alive in 1996, 124 (53.9%) had chronic hepatitis C, 43 (18.7%) were not infected, and 63 (27.4%) had incomplete HCV data. In 2009, 121 (52.6%) were still alive a median of 21.8 years after transfusion. The mortality rate among the HCV‐exposed recipients followed from 1996 was 4.9 per 100 person‐years (PY). The incidence of liver cirrhosis and decompensated cirrhosis was 1.0 per 100 PY and 0.4 per 100 PY, respectively; 16.5% had cirrhosis at death. Among HCV‐exposed recipients, no difference in all‐cause or liver‐related mortality was observed between HCV‐infected and HCV‐uninfected recipients. Further, there was no difference in mortality between HCV‐exposed and ‐unexposed transfusion recipients (mortality rate ratio [MRR], 1.06; 95% confidence interval [CI], 0.96‐1.17; p = 0.47), but liver‐related mortality was significantly higher among HCV‐exposed patients (MRR, 10.0; 95% CI, 7.20‐17.7; p < 0.001).CONCLUSION: Two decades after exposure to blood products from HCV‐infected donors, only 121(11.8%) of 1018 recipients remained alive. For HCV‐exposed recipients no excess all‐cause mortality was observed, but liver‐related mortality was significantly increased.
Serologic characteristics of ceftriaxone antibodies in 25 patients with drug‐induced immune hemolytic anemia (CME)
Authors: Arndt Patricia A. , Leger Regina M. , Garratty George 
Published: September 2011

BACKGROUND: Ceftriaxone, a third‐generation cephalosporin, is commonly used to prevent and treat infections. Since 1987, it has been the second most common cause of drug‐induced immune hemolytic anemia (DIIHA) investigated in our laboratory.STUDY DESIGN AND METHODS: Samples from 79 patients (1987‐2010), suspected of having DIIHA caused by ceftriaxone, were studied for the presence of ceftriaxone antibodies. Direct antiglobulin tests (DATs) and tests with ceftriaxone‐treated red blood cells (RBCs) or untreated and enzyme‐treated RBCs in the presence of ceftriaxone were performed.RESULTS: Twenty‐five (32%) of the 79 patients had antibodies to ceftriaxone detected. Seventeen (68%) of the 25 patients were children; reactions in children were usually dramatic and severe. Nine (36%) of the 25 patients had fatal DIIHA. Nineteen of the 25 samples had DATs performed by our laboratory; 100% of samples were reactive with anti‐C3 and 47% were reactive with anti‐IgG. All 25 sera had ceftriaxone antibodies detected when testing untreated or ficin‐treated RBCs in the presence of ceftriaxone (resulting in agglutination, hemolysis or sensitization of test RBCs). These antibodies were primarily IgM and reactivity was enhanced by testing ficin‐treated RBCs. Sixteen (64%) of the 25 sera reacted with test RBCs when no ceftriaxone was added in vitro; this was most likely due to the transient presence of drug or drug‐immune complexes in the patient's circulation at the time that the blood samples were drawn.CONCLUSION: Ceftriaxone antibodies can cause severe intravascular hemolysis. Complement can usually be detected on the patient's RBCs and IgM antibodies are usually detected in the patient's serum.
Fabrication of Transparent Yttria by High‐Pressure Spark Plasma Sintering
Authors: Zhang Haibin , Kim Byung‐Nam , Morita Koji , Yoshida Hidehiro , Hiraga Keijiro , Sakka Yoshio 
Published: September 2011

Transparent yttria was prepared by means of high‐pressure spark plasma sintering at 1050°C under the uniaxial pressure of 300 MPa. The resulting yttria possessed the in‐line transmittance of 68% at the wavelength of 700 nm and the nanometric grains of about 400 nm. In the near‐infrared spectral region, the transparency of the present specimen approached the level of single crystal yttria. This research highlighted the efficiency and simplicity of high‐pressure spark plasma sintering for fabricating transparent yttria.
Designing of Glass‐FreeLTCCMicrowave Ceramic‐Ca1−x(Li0.5Nd0.5)xWO4by Crystal Chemistry
Authors: Bian Jian Jiang , Wu Jia Yin 
Published: September 2011

Designing guidelines for glass‐free low‐temperature cofired ceramic (LTCC) materials were proposed from the point of view of crystal chemistry. As an example,Ca1−x(Nd0.5Li0.5)xWO4was successfully designed as glass‐freeLTCCmaterials by crystal chemistry. The sintering behavior, microstructure, and microwave dielectric properties ofCa1−x(Nd0.5Li0.5)xWO4ceramics were investigated in this study. The structure and microstructure of the compounds were investigated byX‐ray powder diffraction (XRD) and scanning electron microscopy (SEM). The microwave dielectric properties of the ceramics were studied with a network analyzer at the frequency of about 9–13 GHz. Continuous solid solutionsCa1−x(La0.5Na0.5)xWO4(0.1 ≤ x≤0.5) were formed as expected in the experimented composition range. They could be sintered into dense ceramics (approximately 96%–98% theoretical density) at 825°C–875°C per 2 h. All samples exhibit Scheelite structure (I41/a) phase. Both of the sintering temperature and microwave dielectric properties, especially the temperature coefficient of resonant frequency (τf), could be tuned in a wide range. Combined excellent microwave dielectric properties with εr = 11.7,Q × f = 36 700 GHz, andτf = 5.36 ppm/°C could be obtained for thex = 0.2 composition after sintering at 825°C/2 h. The chemical compatibility ofCa0.8(Nd0.5Li0.5)0.2WO4ceramic with silver (Ag) powders was also investigated. No chemical reaction has taken place between the matrix phase andAgafter sintering at 850°C/2 h. Thus, it can be used as a promising glass‐free microwave dielectric material forLTCCapplications.
Pyrochlore Range from Bi2O3–Fe2O3–TeO3 System for LTCC and Photocatalysis and the Crystal Structure of New Bi3(Fe0.56Te0.44)3O11
Authors: Valant Matjaz , Babu Gunda Santosh , Vrcon Mojca , Kolodiazhnyi Taras , Axelsson Anna‐Karin 
Published: September 2011

A new pyrochlore homogeneity field in Bi2O3–Fe2O3–TeO3 system is characterized with respect to its compositional range and phase relations to adjacent phases. The sintering temperature of these pyrochlores is 880°C and they do not react with metallic silver, which makes them suitable for low‐temperature cofired ceramics (LTCC) technology. Magnetic measurements indicate a spin‐glass formation. The spin freezing temperature that occurs at around 20 K shows a slight, yet systematic, variation with the sample composition. The dielectric constant increases with an increase in Bi content from 37(1) to 55(1). At cryogenic temperatures, they show the dielectric relaxation typical for displacive pyrochlores. The UV–Vis diffuse reflectance data were used for calculation of the electronic band gap. The lowest band gap was determined to be 1.965 eV. Next to the pyrochlore range, another new phase was discovered. Structural analysis showed that Bi3(Fe0.56Te0.44)3O11 crystallizes as KSbO3‐type in a displacive disordered cubic symmetry with a lattice parameter of 9.47045(15) Å.
Sonographic Assessment of the Optic Nerve Sheath and Transorbital Monitoring of Treatment Effects in a Patient with Spontaneous Intracranial Hypotension: Case Report
Authors: Bäuerle Jochen , Gizewski Elke R. , Stockhausen Kerstin von , Rosengarten Bernhard , Berghoff Martin , Grams Astrid E. , Kaps Manfred , Nedelmann Max 
Published: September 2011

ABSTRACTOBJECTIVETo investigate the potential of the ultrasound‐based evaluation of the optic nerve sheath in a patient with spontaneous intracranial hypotension due to cervical cerebrospinal fluid (CSF) leakage.METHODSRepeated measurements of the optic nerve sheath diameter (ONSD) using B‐mode sonography were performed before treatment initiation, during medical treatment, and during a course of repeated placement of epidural blood patches.RESULTSOn admission, transorbital sonography revealed a decreased ONSD of 4.1 mm on the right and 4.3 mm on the left side. After 8 months of treatment with caffeine and computed tomography‐guided epidural blood patches a gradual distension of the ONSD into the normal range was bilaterally observed (right: 5.2 mm; left: 5.3 mm).CONCLUSIONSThe ultrasound‐based evaluation of the optic nerve sheath may be helpful in detecting CSF hypovolemia and for determination of treatment effects. This report should be seen as a basis for future investigations on the sonographic assessment of the optic nerve sheath in diagnosis and treatment of intracranial hypotension.
Arriving by Emergency Medical Services Improves Time to Treatment Endpoints for Patients With Severe Sepsis or Septic Shock
Authors: Band Roger A. , Gaieski David F. , Hylton Julie H. , Shofer Frances S. , Goyal Munish , Meisel Zachary F. 
Published: September 2011

ACADEMIC EMERGENCY MEDICINE 2011; 18:934–940 © 2011 by the Society for Academic Emergency MedicineAbstractObjectives:  The objective was to evaluate the effect of arrival to the emergency department (ED) by emergency medical services (EMS) on time to initiation of antibiotics, time to initiation of intravenous fluids (IVF), and in‐hospital mortality in patients with severe sepsis and septic shock.Methods:  The authors performed an evaluation of prospectively collected registry data of patients with a diagnosis of severe sepsis or septic shock who presented to an urban academic ED during a 2‐year period from January 1, 2005, to December 31, 2006. Descriptive and multivariate analytic methods were used to analyze the data. Using unadjusted and adjusted models, out‐of‐hospital patients who presented to the ED by ambulance (EMS) were compared to control patients who arrived by alternative means (non‐EMS). Primary outcomes measured were ED time to initiation of antibiotics, ED time to initiation of IVF, and in‐hospital mortality.Results:  A total of 963 severe sepsis patients were enrolled in the registry. Median time to antibiotics was 116 minutes for EMS (interquartile range [IQR] = 66 to 199) vs. 152 minutes for non‐EMS (IQR = 92 to 252, p ≤ 0.001). Median time to initiation of IVF was 34 minutes for EMS (IQR = 10 to 88) and 68 minutes for non‐EMS (IQR = 25 to 121, p ≤ 0.001). After adjustment for the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, age, and initial serum lactate level, no significant differences in hospital mortality were seen (adjusted relative risk [aRR] for EMS vs. non EMS = 1.24, 95% confidence interval [CI] = 0.92 to 1.66, p = 0.16). The Cox proportional hazard ratio (HR) comparing EMS to non‐EMS care after similar adjustment was HR = 1.27 for IVF (95% CI = 1.10 to 1.47, p = 0.004) and HR = 1.25 for antibiotics (95% CI = 1.08 to 1.44, p = 0.003).Conclusions:  Out‐of‐hospital care was associated with improved in‐hospital processes for the care of critically ill patients. Despite shortened ED treatment times for septic patients who arrive by EMS, a mortality benefit could not be demonstrated.
Does exercise during pregnancy prevent postnatal depression?
Authors: SONGØYGARD KRISTIAN M. , STAFNE SIGNE N. , EVENSEN KARI ANNE I. , SALVESEN KJELL Å. , VIK TORSTEIN , MØRKVED SIV 
Published: September 2011

AbstractObjective. To study whether exercise during pregnancy reduces the risk of postnatal depression. Design. Randomized controlled trial. Setting. Trondheim and Stavanger University Hospitals, Norway. Population and Sample. Eight hundred and fifty‐five pregnant women were randomized to intervention or control groups. Methods. The intervention was a 12week exercise program, including aerobic and strengthening exercises, conducted between week 20 and 36 of pregnancy. One weekly group session was led by physiotherapists, and home exercises were encouraged twice a week. Control women received regular antenatal care. Main Outcome Measures. Edinburgh Postnatal Depression Scale (EPDS) completed three months after birth. Scores of 10 or more and 13 or more suggested probable minor and major depression, respectively. Results. Fourteen of 379 (3.7%) women in the intervention group and 17 of 340 (5.0%) in the control group had an EPDS score of ≥10 (p=0.46), and four of 379 (1.2%) women in the intervention group and eight of 340 (2.4%) in the control group had an EPDS score of ≥13 (p=0.25). Among women who did not exercise prior to pregnancy, two of 100 (2.0%) women in the intervention group and nine of 95 (9.5%) in the control group had an EPDS score of ≥10 (p=0.03). Conclusions. We did not find a lower prevalence of high EPDS scores among women randomized to regular exercise during pregnancy compared with the control group. However, a subgroup of women in the intervention group who did not exercise regularly prior to pregnancy had a reduced risk of postnatal depression.
Genetic variations in multiple myeloma II: association with effect of treatment
Authors: Vangsted Annette , Klausen Tobias W. , Vogel Ulla 
Published: September 2011

AbstractAssociation studies on genetic variation to treatment effect may serve as a predictive marker for effect of treatment and can also uncover biological pathways behind drug effect. Single‐nucleotide polymorphisms (SNPs) have been studied in relation to high‐dose treatment (HDT), thalidomide‐ and bortezomib‐based therapy, maintenance treatment with interferon‐α and in relation to therapy‐related adverse effects caused by treatment. Candidate genes for prediction of effect of HDT include DNA repair genes, CYP genes and genes involved in inflammation and apoptosis such as IL1B and RAI. In thalidomide‐ and bortezomid‐based therapy, candidate genes include TNFA and genes involved in the nuclear factor kappa B pathway (NFKB2 and TRAF3), respectively. In maintenance treatment with interferon‐α, a polymorphism in gene NFKB1 is a candidate gene for prediction for effect. Adverse effect includes infection, osteonecrosis of the jaw (ONJ), venous thrombotic events (VTE) and peripheral neuropathy (PN). A SNP in MBL2 and MPO gene was associated with septicemia and a SNP in the gene CYP2C8 was strongly associated with ONJ. Several SNPs in genes encoding DNA repair, apoptosis, inflammation and genes involved in function of the nervous system have been associated with VTE induced by thalidomide and with PN induced by bortezomib. SNP analysis is simple and can be performed, e.g., on blood and buccal cells. Further analysis of SNPs in clinical trials is needed, and collaboration between scientific groups will be an advantage because SNP analysis required large number of patients.