bluuebunny/crossref_metadata_2025_split huggingface dataset:
Load-induced changes in ventricular repolarization: evidence of autonomic modulation
Authors: Sedova Ksenia A. , Goshka Sergey L. , Vityazev Vladimir A. , Shmakov Dmitriy N. , Azarov Jan E. 
Published: November 2011

Augmented hemodynamic load increases the risk of arrhythmogenesis by modulating cardiac repolarization duration. We hypothesized that the intervention on the autonomic tone may affect the load-dependent changes in ventricular repolarization. Activation–recovery intervals were measured in unipolar electrograms simultaneously recorded from 64 ventricular epicardial leads, in a total of 26 chinchilla rabbits in resting conditions, and after 1 and 10 min of aortic stenosis. Eleven animals were given atropine and propranolol before the loading. The short-term stenosis decreased the activation–recovery intervals in the right ventricle, whereas the prolonged overload increased the repolarization duration in both ventricles. The treatment with the β-adrenergic and M-cholinergic blockers prolonged the activation–recovery intervals, especially at the left ventricle, attenuating the apicobasal and interventricular gradients of repolarization duration seen in the baseline state. Further ventricular loading shortened the repolarization duration in both ventricles in animals with autonomic blockade. Thus, the autonomic tone was shown to be essential for the development of repolarization heterogeneity across the ventricles. The autonomic blockade transformed the biphasic changes of activation–recovery intervals into their monophasic shortening at aortic stenosis.
Developmental expression and organisation of fibrinogen genes in the zebrafish
Authors: Vorjohann Silja , Béna Frédérique , Fort Alexandre , Fish Richard J. , Neerman-Arbez Marguerite 
Published: November 2011

SummaryThe zebrafish is a model organism for studying vertebrate development and many human diseases. Orthologues of the majority of human coagulation factors are present in zebrafish, including fibrinogen. As a first step towards using zebrafish to model human fibrinogen disorders, we cloned the zebrafish fibrinogen cDNAs and made in situ hybridisations and quantitative reverse transcription-polymerase chain reactions (qRT-PCR) to detect zebrafish fibrinogen mRNAs. Prior to liver development or blood flow we detected zebrafish fibrinogen expression in the embryonic yolk syncytial layer and then in the early cells of the developing liver. While human fibrinogen is encoded by a three-gene, 50 kilobase (kb) cluster on chromosome 4 (FGB-FGA-FGG), recent genome assemblies showed that the zebrafish fgg gene appears distanced from fga and fgb, which we confirmed by in situ hybridisation. The zebrafish fibrinogen Bβ and γ protein chains are conserved at over 50% of amino acid positions, compared to the human polypeptides. The zebrafish Aα chain is less conserved and its C-terminal region is nearly 200 amino acids shorter than human Aα. We generated transgenic zebrafish which express a green fluorescent protein reporter gene under the control of a 1.6 kb regulatory region from zebrafish fgg. Transgenic embryos showed strong fluorescence in the developing liver, mimicking endogenous fibrinogen expression. This regulatory sequence can now be used for overexpression of transgenes in zebrafish hepatocytes. Our study is a proof-of-concept step towards using zebrafish to model human disease linked to fibrinogen gene mutations.
Long-term therapy with low-molecular-weight heparin in cancer patients with venous thromboembolism
Authors: Marchena Pablo , Nieto José , Guil María , García-Bragado Ferrán , Rabuñal Ramón , Boccalon Henri , Trujillo-Santos Javier , Monreal Manuel ,   RIETE Investigators
Published: November 2011

SummaryLong-term therapy with low-molecular-weight heparin (LMWH) is the treatment of choice for cancer patients with venous thromboembolism (VTE). However, the ideal doses of LMWH have not been thoroughly studied. We used the RIETE Registry data to assess the influence of the daily LMWH dosage on outcome during the first three months after VTE. We used propensity score-matching to compare patients who received <150 vs. those receiving ≥150 UI/kg/day LMWH. Up to July 2010, 3,222 cancer patients with VTE received long-term therapy with fixed doses of LMWH. Of these, 1,472 (46%) received <150 IU/kg/day (mean, 112 ± 28), and 1,750 received ≥150 IU/kg/day (mean, 184 ± 32). Results of the propensity score matching involved 1269 matched pairs. During follow-up, the incidence of pulmonary embolism (PE) recurrences was similar (1.2% vs. 1.9%), but patients receiving <150 IU/kg/day LMWH had a lower incidence of fatal PE than those treated with ≥150 IU/kg/day (0.2% vs. 1.0%; p=0.004). Multivariate analysis confirmed that patients receiving <150 IU/kg/day LMWH had a lower risk for fatal PE (odds ratio [OR]: 0.2; 95% confidence interval [CI]: 0.06–0.8) and for major bleeding (OR: 0.6; 95% CI: 0.3–1.0) than those treated with ≥150 IU/kg/day. In real life, one in every two cancer patients with VTE received lower doses of LMWH than those used in randomised trials, with large variations from patient to patient. Unexpectedly, patients treated with <150 IU/kg/day LMWH had fewer fatal PE cases and fewer major bleeding events than those receiving ≥150 IU/kg/day LMWH. This finding, however, should be validated in prospective clinical trials.
A point mutation in the EGF-4 domain of β3 integrin is responsible for the formation of the Seca platelet alloantigen and affects receptor function
Authors: Sachs Ulrich J. , Bakchoul Tamam , Eva Olga , Giptner Astrid , Bein Gregor , Aster Richard H. , Gitter Maria , Peterson Julie , Santoso Sentot 
Published: November 2011

SummaryNeonatal alloimmune thrombocytopenia (NAIT) is caused by fetomaternal platelet incompatibility with maternal antibodies crossing the placenta and destroying fetal platelets. Antibodies against human platelet antigen-1a (HPA-1a) and HPA-5b are responsible for the majority of NAIT cases. We observed a suspected NAIT in a newborn with a platelet count of 25 G/l and petechial haemorrhages. Serological analysis of maternal serum revealed an immunisation against αIIbβ3 on paternal platelets only, indicating the presence of an antibody against a new rare alloantigen (Seca) residing on αIIbβ3. The location of Seca on αIIbβ3 was confirmed by immunoprecipitation. Nucleotide sequence analysis of paternal β3 revealed a single nucleotide exchange (G1818T) in exon 11 of the β3 gene (ITGB3), changing Lys580 (wild-type) to Asn580 (Seca). Two additional members of the family Sec were typed Seca positive, but none of 300 blood donors. Chinese hamster ovary cells expressing Asn580, but not Lys580 αIIbβ3, bound anti-Seca, which was corroborated by immunoprecipitation. Adhesion of transfected cells onto immobilised fibrinogen showed reduced binding of the Asn580 variant compared to wild-type αIIbβ3. Analysis of transfected cells with anti-LIBS and PAC-1 antibody showed reduced binding when compared to the wild-type. No such effects were observed with Seca positive platelets, which, however, are heterozygous for the Lys580Asn mutation. In this study, we describe a NAIT case caused by maternal alloimmunisation against a new antigen on αIIbβ3. Analysis with mutant transfected cells showed that the Lys580Asn mutation responsible for the formation of the Seca antigenic determinant affects αIIbβ3 receptor function.
Prescription patterns in preventive and abortive migraine medication
Authors: Sumelahti Marja-Liisa , Mattila Kari , Sillanmäki Lauri , Sumanen Markku 
Published: November 2011

Background: Migraine is considered a common but under-diagnosed and untreated condition. Treatment patterns have pointed at frequent over-the-counter medication use and low use of preventive therapies. Studies exploring migraine prescription practice among doctors are few. Methods: A population-based study was carried out to examine the prescription practice in the use of acute and preventive migraine medications. The data covered 4864 working-age people reporting they have been diagnosed with migraine. Data on reimbursed prescription medicines from 1 January 1998 to 31 December 2006 were drawn from the registers of the Social Insurance Institute of Finland and compared with age- and sex-matched controls. Results: Anti-inflammatory analgesics were prescribed for 71% of female and 62% of male migraine patients vs. 56% and 50% of controls. Triptans were prescribed for 21% of female and 10% of male patients. Combinations of analgesics and muscle relaxants were offered to 37% of female and 29% of male patients vs. 26% and 21% of controls, and antidepressants to 19% of women and 14% of men vs. 13% and 9% of controls. Conclusion: Although use of preventive medication among migraineurs was high, the prescription patterns in acute treatments showed that NSAIDS were used more often than triptans. Assimilation of national guidelines to treat migraine published in 2002 in Finland was not reflected in the prescription patterns up to 2006.
Immortalized mesenchymal stem cells: an alternative to primary mesenchymal stem cells in neuronal differentiation and neuroregeneration associated studies
Authors: Gong Min , Bi Yang , Jiang Wei , Zhang Yun , Chen Li , Hou Nali , Liu Youxue , Wei Xiaoping , Chen Jie , Li Tingyu 
Published: November 2011

AbstractBackgroundMesenchymal stem cells (MSCs) can be induced to differentiate into neuronal cells under appropriate cellular conditions and transplanted in brain injury and neurodegenerative diseases animal models for neuroregeneration studies. In contrast to the embryonic stem cells (ESCs), MSCs are easily subject to aging and senescence because of their finite ability of self-renewal. MSCs senescence seriously affected theirs application prospects as a promising tool for cell-based regenerative medicine and tissue engineering. In the present study, we established a reversible immortalized mesenchymal stem cells (IMSCs) line by using SSR#69 retrovirus expressing simian virus 40 large T (SV40T) antigen as an alternative to primary MSCs.MethodsThe retroviral vector SSR#69 expressing simian virus 40 large T (SV40T) antigen was used to construct IMSCs. IMSCs were identified by flow cytometry to detect cell surface makers. To investigate proliferation and differentiation potential of IMSCs, cell growth curve determination and mesodermal trilineage differentiation tests were performed. Neuronal differentiation characteristics of IMSCs were detectedin vitro. Before IMSCs transplantation, we excluded its tumorigenicity in nude mice firstly. The Morris water maze tests and shuttle box tests were performed five weeks after HIBD models received cells transplantation therapy.ResultsIn this study, reversible IMSCs were constructed successfully and had the similar morphology and cell surface makers as primary MSCs. IMSCs possessed better ability of proliferation and anti-senescence compared with primary MSCs, while maintained multilineage differentiation capacity. Neural-like cells derived from IMSCs had similar expressions of neural-specific genes, protein expression patterns and resting membrane potential (RMP) compared with their counterparts derived from primary MSCs. There was no bump formation in nude mice subcutaneously injected with IMSCs. IMSCs played same role as primary MSCs to improve learning ability and spatial memory of HIBD rats.ConclusionsIMSCs not only retain their features of primary MSCs but also possess the ability of high proliferation and anti-senescence. IMSCs can definitely be induced to differentiate into neuronal cellsin vitroand take the place of primary MSCs for cell transplantation therapy without tumorigenesisin vivo. The stable cell line is particularly useful and valuable as an alternative to MSCs in neuronal differentiation and neuroregeneration associated studies.
NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines
Authors: Tsofack Serges P , Garand Chantal , Sereduk Chris , Chow Donald , Aziz Meraj , Guay David , Yin Hongwei H , Lebel Michel 
Published: November 2011

Abstract

Background
YB-1 is a multifunctional protein that affects transcription, splicing, and translation. Overexpression of YB-1 in breast cancers causes cisplatin resistance. Recent data have shown that YB-1 is also overexpress in colorectal cancer. In this study, we tested the hypothesis that YB-1 also confers oxaliplatin resistance in colorectal adenocarcinomas.

Results
We show for the first time that transfection of YB-1 cDNA confers oxaliplatin resistance in two colorectal cancer cell lines (SW480 and HT29 cell lines). Furthermore, we identified by mass spectrometry analyses important YB-1 interactors required for such oxaliplatin resistance in these colorectal cancer cell lines. A tagged YB-1 construct was used to identify proteins interacting directly to YB-1 in such cells. We then focused on proteins that are potentially involved in colorectal cancer progression based on the Oncomine microarray database. Genes encoding for these YB-1 interactors were also examined in the public NCBI comparative genomic hybridization database to determine whether these genes are localized to regions of chromosomes rearranged in colorectal cancer tissues. From these analyses, we obtained a list of proteins interacting with YB-1 and potentially involved in oxaliplatin resistance. Oxaliplatin dose response curves of SW480 and HT29 colorectal cancer cell lines transfected with several siRNAs corresponding to each of these YB-1 interactors were obtained to identify proteins significantly affecting oxaliplatin sensitivity upon gene silencing. Only the depletion of either NONO or RALY sensitized both colorectal cancer cell lines to oxaliplatin. Furthermore, depletion of NONO or RALY sensitized otherwise oxaliplatin resistant overexpressing YB-1 SW480 or HT29 cells.

Conclusion
These results suggest knocking down NONO or RALY significant counteracts oxaliplatin resistance in colorectal cancers overexpressing the YB-1 protein.
Identification and thermochemical analysis of high-lignin feedstocks for biofuel and biochemical production
Authors: Mendu Venugopal , Harman-Ware Anne E , Crocker Mark , Jae Jungho , Stork Jozsef , Morton Samuel , Placido Andrew , Huber George , DeBolt Seth 
Published: November 2011

Abstract

Background
Lignin is a highly abundant biopolymer synthesized by plants as a complex component of plant secondary cell walls. Efforts to utilize lignin-based bioproducts are needed.

Results
Herein we identify and characterize the composition and pyrolytic deconstruction characteristics of high-lignin feedstocks. Feedstocks displaying the highest levels of lignin were identified as drupe endocarp biomass arising as agricultural waste from horticultural crops. By performing pyrolysis coupled to gas chromatography-mass spectrometry, we characterized lignin-derived deconstruction products from endocarp biomass and compared these with switchgrass. By comparing individual pyrolytic products, we document higher amounts of acetic acid, 1-hydroxy-2-propanone, acetone and furfural in switchgrass compared to endocarp tissue, which is consistent with high holocellulose relative to lignin. By contrast, greater yields of lignin-based pyrolytic products such as phenol, 2-methoxyphenol, 2-methylphenol, 2-methoxy-4-methylphenol and 4-ethyl-2-methoxyphenol arising from drupe endocarp tissue are documented.

Conclusions
Differences in product yield, thermal decomposition rates and molecular species distribution among the feedstocks illustrate the potential of high-lignin endocarp feedstocks to generate valuable chemicals by thermochemical deconstruction.
Distribution of Rickettsia rickettsii in ovary cells of Rhipicephalus sanguineus (Latreille1806) (Acari: Ixodidae)
Authors: da Silva Costa Luís Flávio , Nunes Pablo Henrique , Soares João Fábio , Labruna Marcelo Bahia , Camargo-Mathias Maria Izabel 
Published: November 2011

Abstract

Background
Considering the fact that the dog tick, Rhipicephalus sanguineus, has a great potential to become the vector of Brazilian Spotted Fever (BSF) for humans, the present study aimed to describe the distribution of the bacterium Rickettsia rickettsii, the etiological agent of BSF, in different regions of the ovaries of R. sanguineus using histological techniques. The ovaries were obtained from positive females confirmed by the hemolymph test and fed in the nymph stage on guinea pigs inoculated with R. rickettsii.

Results
The results showed a general distribution of R. rickettsii in the ovary cells, being found in oocytes in all stages of development (I, II, III, IV and V) most commonly in the periphery of the oocyte and also in the cytoplasm of pedicel cells.

Conclusions
The histological analysis of the ovaries of R. sanguineus infected females confirmed the presence of the bacterium, indicating that the infection can interfere negatively in the process of reproduction of the ticks, once alterations were detected both in the shape and cell structure of the oocytes which contained bacteria.
A five-year prospective study of fatigue in primary Sjögren's syndrome
Authors: Haldorsen Karstein , Bjelland Ingvar , Bolstad Anne Isine , Jonsson Roland , Brun Johan Gorgas 
Published: November 2011

Abstract

Introduction

Fatigue is prevalent in primary Sjögren's syndrome (pSS), and contributes to the considerably reduced health related quality of life in this disease. The symptom is included in proposed disease activity and outcome measures for pSS. Several studies indicate that there is an inflammatory component of fatigue in pSS and other chronic inflammatory rheumatic diseases. The purpose of this study was to investigate fatigue change in pSS in a longitudinal study, and explore whether any clinical or laboratory variables at baseline, including serum cytokines, were associated with a change in fatigue scores over time.

Methods

A clinical and laboratory investigation of 141 patients fulfilling the American-European consensus criteria of pSS was undertaken in the period May 2004 to April 2005. Median time since diagnosis was 5.5 years. Examinations included the fatigue questionnaires: fatigue severity scale (FSS), fatigue visual analogue scale (VAS), functional assessment of chronic illness therapy - fatigue (FACIT-F) and medical outcome study short form-36 (SF-36) vitality, which were repeated in a follow-up investigation in January and February 2010.

Results

A total of 122 patients (87%) responded at both time-points. Thirty-five percent of patients experienced a clinically significant FSS increase. On the group level, fatigue measures did not change except that there was a slight deterioration in SF-36 vitality score. High serum anti-Sjögren's syndrome A antigen (anti-SSA) showed weak associations with high baseline fatigue, and patients with increasing fatigue had lower baseline unstimulated whole salivary volume. Weak associations between increasing fatigue and serum immunoglobulin G (IgG), and the pro-inflammatory cytokine interleukin-17 (IL-17), were observed. Baseline sicca symptoms correlated with higher fatigue both at baseline and with increasing fatigue over time. Linear regression analysis did not identify any predictive ability of clinical or laboratory measures on fatigue change over time.

Conclusions

Fatigue remained mainly unchanged over time. Using multivariate models did not reveal any clinical or laboratory predictors of fatigue change over time.
Minocycline and doxycycline therapy in community patients with rheumatoid arthritis: prescribing patterns, patient-level determinants of use, and patient-reported side effects
Authors: Smith Christopher J , Sayles Harlan , Mikuls Ted R , Michaud Kaleb 
Published: November 2011

Abstract
Introduction
Minocycline and doxycycline are safe and moderately effective disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of early, DMARD-naïve rheumatoid arthritis (RA), although little is known about their use outside clinical trials. We characterize the use of minocycline and doxycycline in community-dwelling RA patients by examining associated prescribing patterns, patient-level determinants of use, and side-effect profiles.

Methods
We studied 15,716 patients with RA observed between 1998 and 2009 while participating in a long-term US observational study.

Results
Minocycline or doxycycline was prescribed by 18% of rheumatologists (interquartile range one to two patients per physician) to 9% of RA patients. Significant differences between minocycline-treated and doxycycline-treated patients and nontreated patients included age (58.4 years vs. 59.8 years), RA duration (14.8 years vs. 13.7 years), Caucasian race (93.7% vs. 89.7%), lifetime DMARDs and biologics (3.3 vs. 2.5), prednisone use (40.1% vs. 35.3%), and Medical Outcomes Study 36-Item Short Form Survey physical component summary score (35.0 vs. 36.4). In multivariable Cox regression, patients initiating minocycline or doxycycline had increased disease activity, more comorbidities, and a greater number of prior nonbiologic DMARDs. Side effects were reported by 17.8% of minocycline users and 11.8% of doxycycline users. Skin complaints accounted for 54% of minocycline patient-reported side effects. The most commonly effected organ systems for doxycycline were gastrointestinal (35.4%) and skin (33.7%). Approximately 75% of side effects were of mild or moderate severity.

Conclusions
Rheumatologists have not embraced minocycline or doxycycline as primary treatment options for RA and reserve their use primarily in patients with long-standing, refractory disease. These drugs are generally well tolerated, with skin complaints, nausea, and dizziness being the most common patient-reported side effects.
Effectiveness of cognitive behaviour therapy for the treatment of catastrophisation in patients with fibromyalgia: a randomised controlled trial
Authors: Alda Marta , Luciano Juan V , Andrés Eva , Serrano-Blanco Antoni , Rodero Baltasar , del Hoyo Yolanda López , Roca Miquel , Moreno Sergio , Magallón Rosa , García-Campayo Javier 
Published: November 2011

Abstract

Introduction

No randomised, controlled trials have been conducted to date on the efficacy of psychological and pharmacological treatments of pain catastrophising (PC) in patients with fibromyalgia. Our aim in this study was to assess the effectiveness of cognitive-behaviour therapy (CBT) and the recommended pharmacological treatment (RPT) compared with treatment as usual (TAU) at the primary care level for the treatment of PC in fibromyalgia patients.

Methods

We conducted a six-month, multicenter, randomized, blinded, parallel group, controlled trial in which patients were randomly assigned to one of three study arms: CBT (n = 57), RPT (n = 56) and TAU at the primary care level (n = 56). The major outcome of this study was PC in patients with fibromyalgia. The secondary variables were pain acceptance, depression, anxiety, pain, global function and quality of life.

Results

CBT significantly decreased global PC at the six-month follow-up examination with effect sizes of Cohen's d = 0.73 and 1.01 compared with RPT and TAU, respectively. CBT was also more effective than RPT and TAU at increasing pain acceptance at the six-month follow-up examination (effect sizes of Cohen's d = 0.77 and 0.80, respectively). Compared with RPT and TAU, CBT was more effective at improving global function based on the Fibromyalgia Impact Questionnaire (six-month effect sizes Cohen's d = 0.44 and 0.53, respectively) and quality of life based on the European Quality of Life Scale (six-month effect sizes Cohen's d = 0.11 and 0.40, respectively). There were no differences among the three treatments with regard to pain and depression.

Conclusions

CBT shows higher efficacy than RPT and TAU not only in key outcomes in FM, such as function and quality of life, but also in relevant mediators of treatment effects, such as pain catastrophising and pain acceptance.

Trial registration

ISRCTN: ISRCTN10804772