bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of BACE1 expression by oxidative and nitrosative signals
Authors: Kwak Young-Don , Wang Ruishan , Li Jing Jing , Zhang Yun-Wu , Xu Huaxi , Liao Francesca-Fang 
Published: March 2011

Abstract

Background
It is well established that both cerebral hypoperfusion/stroke and type 2 diabetes are risk factors for Alzheimer's disease (AD). Recently, the molecular link between ischemia/hypoxia and amyloid precursor protein (APP) processing has begun to be established. However, the role of the key common denominator, namely nitric oxide (NO), in AD is largely unknown. In this study, we investigated redox regulation of BACE1, the rate-limiting enzyme responsible for the β-cleavage of APP to Aβ peptides.

Results
Herein, we studied events such as S-nitrosylation, a covalent modification of cysteine residues by NO, and H2O2-mediated oxidation. We found that NO and H2O2 differentially modulate BACE1 expression and enzymatic activity: NO at low concentrations (<100 nM) suppresses BACE1 transcription as well as its enzymatic activity while at higher levels (0.1-100 μM) NO induces S-nitrosylation of BACE1 which inactivates the enzyme without altering its expression. Moreover, the suppressive effect on BACE1 transcription is mediated by the NO/cGMP-PKG signaling, likely through activated PGC-1α. H2O2 (1-10 μM) induces BACE1 expression via transcriptional activation, resulting in increased enzymatic activity. The differential effects of NO and H2O2 on BACE1 expression and activity are also reflected in their opposing effects on Aβ generation in cultured neurons in a dose-dependent manner. Furthermore, we found that BACE1 is highly S-nitrosylated in normal aging brains while S-nitrosylation is markedly reduced in AD brains.

Conclusion
This study demonstrates for the first time that BACE1 is highly modified by NO via multiple mechanisms: low and high levels of NO suppress BACE1 via transcriptional and post translational regulation, in contrast with the upregulation of BACE1 by H2O2-mediated oxidation. These novel NO-mediated regulatory mechanisms likely protect BACE1 from being further oxidized by excessive oxidative stress, as from H2O2 and peroxynitrite which are known to upregulate BACE1 and activate the enzyme, resulting in excessive cleavage of APP and Aβ generation; they likely represent the crucial house-keeping mechanism for BACE1 expression/activation under physiological conditions.
CDCOCA: A statistical method to define complexity dependence of co-occuring chromosomal aberrations
Authors: Kumar Nitin , Rehrauer Hubert , Cai Haoyang , Baudis Michael 
Published: March 2011

AbstractBackgroundCopy number alterations (CNA) play a key role in cancer development and progression. Since more than one CNA can be detected in most tumors, frequently co-occurring genetic CNA may point to cooperating cancer related genes. Existing methods for co-occurrence evaluation so far have not considered the overall heterogeneity of CNA per tumor, resulting in a preferential detection of frequent changes with limited specificity for each association due to the high genetic instability of many samples.MethodWe hypothesize that in cancer some linkage-independent CNA may display a non-random co-occurrence, and that these CNA could be of pathogenetic relevance for the respective cancer. We also hypothesize that the statistical relevance of co-occurring CNA may depend on the sample specific CNA complexity. We verify our hypotheses with a simulation based algorithm CDCOCA (complexity dependence of co-occurring chromosomal aberrations).ResultsApplication of CDCOCA to example data sets identified co-occurring CNA from low complex background which otherwise went unnoticed. Identification of cancer associated genes in these co-occurring changes can provide insights of cooperative genes involved in oncogenesis.ConclusionsWe have developed a method to detect associations of regional copy number abnormalities in cancer data. Along with finding statistically relevant CNA co-occurrences, our algorithm points towards a generally low specificity for co-occurrence of regional imbalances in CNA rich samples, which may have negative impact on pathway modeling approaches relying on frequent CNA events.
International web survey of chiropractic students about evidence-based practice: a pilot study
Authors: Banzai Ryunosuke , Derby Dustin C , Long Cynthia R , Hondras Maria A 
Published: March 2011

AbstractBackgroundPositive attitude toward evidence-based practice (EBP) principles in healthcare education may be one of the first steps for motivating a healthcare professional student to later apply EBP principles in clinical decision-making. The objectives for this project were to pilot an international web-based survey of chiropractic students and to describe student attitudes, behaviors, and knowledge about EBP principles.MethodsWe used SurveyMonkey™ to develop our survey based on an existing questionnaire used to measure basic knowledge, skills and beliefs about EBP among allied healthcare professionals and CAM practitioners. We invited 26 chiropractic educational institutions teaching in English and accredited by official organizations to participate. Academic officials and registrars at participating institutions forwarded an invitation email and two reminders to students between July and September 2010. The invitation contained a link to the 38-item web-based questionnaire. Descriptive statistics were performed for analysis.ResultsFourteen institutions from Australia, Canada, US, Denmark and New Zealand participated. Among an estimated 7,142 student recipients of invitation letters, 674 participated in the survey for an estimated response rate of 9.4%. Most respondents reported having access to medical/healthcare literature through the internet, but only 11% read literature every week and 21% did not read literature at all. Respondents generally agreed that the use of research evidence in chiropractic was important. Although 76% of respondents found it easy to understand research evidence and 81% had some level of confidence assessing the general worth of research articles, 71% felt they needed more training in EBP to be able to apply evidence in chiropractic care. Respondents without previous training in research methods had lower confidence in assessing published papers. While more than 60% marked the correct answer for two knowledge items, the mean number of correct answers to the five knowledge questions was 1.3 (SD 0.9).ConclusionsAlthough it is feasible to conduct an international web survey of chiropractic students, significant stakeholder participation is important to improve response rates. Students had relatively positive attitudes toward EBP. However, participants felt they needed more training in EBP and based on the knowledge questions they may need further training about basic research concepts.
Detection of cancer cells in the cerebrospinal fluid: current methods and future directions
Authors: Weston Cody L , Glantz Michael J , Connor James R 
Published: March 2011

AbstractThe spread of cancer into the central nervous system is a serious problem leading to neurological symptoms and rapid mortality. The current tools available for detecting the spread of cancer into the cerebrospinal fluid (CSF) are cytology, neurologic examination, and neuroimaging. All three of these methods can be applied in concert to reach a diagnosis, but they all suffer from a lack of sensitivity, leading to delays in treatment in many cases. An overview of research tools in the field of CSF cancer detection reveals a variety of promising technologies that can be used to answer questions about the biology of metastatic cancer and to develop more powerful clinical detection methods. Methods currently under investigation include new immunocytochemistry methods and flow cytometry for thein vitrodetection of cells. Additionally, polymerase chain reaction, fluorescencein situhybridization, capillary electrophoresis with laser-induced fluorescence, and mass spectrometry using matrix-assisted laser absorption-deionization time-of-flight and surface-enhanced laser desorption/ionization time-of-flight techniques are being tested forin vitroassessment of the non-cellular biomarkers in CSF. Forin vivodetection of cancer in the CSF, research techniques include certain quantum dot platforms as well as magnetic iron oxide nanoparticles. As systemic therapies for cancer improve, the CNS is becoming a more common site of disease recurrence. This increases the importance of effective detection methods in the CSF, since early intervention can maximize therapeutic benefit. Furthermore, many cell-based detection methods can be combined with therapeutic agents to serve multiple medical functions through a common targeting system.
Contemporary epidemiology of gout in the UK general population
Authors: Cea Soriano Lucía , Rothenbacher Dietrich , Choi Hyon K , García Rodríguez Luis A 
Published: March 2011

Abstract
Introduction
The objective of this study was to investigate the contemporary incidence of gout, examine potential risk factors, and evaluate specific gout treatment patterns in the general population.

Methods
Using the health improvement network (THIN) UK primary care database, we estimated the incidence of gout based on 24,768 newly diagnosed gout patients among a cohort of 1,775,505 individuals aged 20 to 89 years between 2000 and 2007. We evaluated potential risk factors for incident gout in a nested case-control study with 50,000 controls frequency-matched by age, sex and calendar time. We calculated odds ratios (OR) by means of unconditional logistic regression adjusting for demographic variables, lifestyle variables, relevant medical conditions and drug exposures.

Results
The incidence of gout per 1,000 person-years was 2.68 (4.42 in men and 1.32 in women) and increased with age. Conventional risk factors were significantly and strongly associated with the risk of gout, with multivariate ORs of 3.00 (95% confidence interval (CI)) for excessive alcohol intake (that is, more than 42 units per week), 2.34 (95% CI 2.22 to 2.47) for obesity (body mass index > = 30 kg/m2), 2.48 (95% CI 2.19 to 2.81) for chronic renal impairment, and 3.00 (95% CI 2.85 to 3.15) for current diuretic use. For other medical conditions the multivariate OR were 1.84 (95% CI 1.70 to 2.00) for heart failure, 1.45 (95% CI 1.18 to 1.79) for hypertriglyceridemia and 1.12 (95% CI 1.04 to 1.22) for psoriasis. Use of cyclosporine was associated with an OR of 3.72 (95% CI, 2.17 to 6.40). Among gout-specific therapies, allopurinol was the most frequently used with a one-year cumulative incidence of 28% in a cohort of incident gout diagnosed from 2000 to 2001. Use of gout-specific treatment has not changed over recent years except for an increase of colchicine.

Conclusions
The contemporary incidence of gout in UK remains substantial. In this general population cohort, associations with previously purported risk factors were evident including psoriasis, heart failure, hypertriglyceridemia, and cyclosporine therapy. Use of gout-specific treatment has remained relatively constant in recent years except for an increase of colchicine.
The effect of window rooms on critically ill patients with subarachnoid hemorrhage admitted to intensive care
Authors: Wunsch Hannah , Gershengorn Hayley , Mayer Stephan A , Claassen Jan 
Published: March 2011

Abstract
Introduction
Clinicians and specialty societies often emphasize the potential importance of natural light for quality care of critically ill patients, but few studies have examined patient outcomes associated with exposure to natural light. We hypothesized that receiving care in an intensive care unit (ICU) room with a window might improve outcomes for critically ill patients with acute brain injury.

Methods
This was a secondary analysis of a prospective cohort study. Seven ICU rooms had windows, and five ICU rooms did not. Admission to a room was based solely on availability.
We analyzed data from 789 patients with subarachnoid hemorrhage (SAH) admitted to the neurological ICU at our hospital from August 1997 to April 2006. Patient information was recorded prospectively at the time of admission, and patients were followed up to 1 year to assess mortality and functional status, stratified by whether care was received in an ICU room with a window.

Results
Of 789 SAH patients, 455 (57.7%) received care in a window room and 334 (42.3%) received care in a nonwindow room. The two groups were balanced with regard to all patient and clinical characteristics. There was no statistical difference in modified Rankin Scale (mRS) score at hospital discharge, 3 months or 1 year (44.8% with mRS scores of 0 to 3 with window rooms at hospital discharge versus 47.2% with the same scores in nonwindow rooms at hospital discharge; adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 0.67 to 1.50, P = 0.98; 62.7% versus 63.8% at 3 months, aOR 0.85, 95% CI 0.58 to 1.26, P = 0.42; 73.6% versus 72.5% at 1 year, aOR 0.78, 95% CI 0.51 to 1.19, P = 0.25). There were also no differences in any secondary outcomes, including length of mechanical ventilation, time until the patient was able to follow commands in the ICU, need for percutaneous gastrostomy tube or tracheotomy, ICU and hospital length of stay, and hospital, 3-month and 1-year mortality.

Conclusions
The presence of a window in an ICU room did not improve outcomes for critically ill patients with SAH admitted to the ICU. Further studies are needed to determine whether other groups of critically ill patients, particularly those without acute brain injury, derive benefit from natural light.
Differential miRNA Expression in Omental Adipose Tissue and in the Circulation of Obese Patients Identifies Novel Metabolic Biomarkers
Authors: Heneghan H. M. , Miller N. , McAnena O. J. , O'Brien T. , Kerin M. J. 
Published: March 2011

Background:
Omental fat accumulation is associated with development of the metabolic syndrome, although its molecular characteristics are poorly understood. Mi(cro)RNAs (miRNAs), a class of small noncoding RNAs, are known to regulate various metabolic processes, although their role in obesity and the metabolic syndrome is not clearly defined. This study sought to characterize the miRNA expression in omentum, sc fat and in the circulation of obese and nonobese individuals. Their potential as noninvasive metabolic biomarkers was also explored.

Methods:
miRNA was extracted from paired omentum and sc fat tissues, and blood samples, from a total of 50 obese and nonobese patients. A miRNA microarray was performed and a panel of differentially expressed miRNAs validated using RQ-PCR.

Results:
The miRNA expression profiles were unique for omentum and paired sc fat; no correlation in miRNA expression was observed between these two fat depots. Expression of two miRNAs (miR-17–5p and miR-132) differed significantly between obese and nonobese omental fat (P = 0.048 and P = 0.016). This expression pattern was reflected in the circulation in which these same two miRNAs were also significantly dysregulated in blood from obese subjects. The miRNA expression in omental fat and blood from obese patients correlated significantly with body mass index, fasting blood glucose, and glycosylated hemoglobin.

Conclusion:
This study demonstrates that candidate metabolic miRNAs are altered in adipose tissue and circulation of the obese. Omental fat tissue and systemic miRNA levels reflect components of the metabolic syndrome, highlighting their potential as novel biomarkers for this complex syndrome.
Selective Solid-Phase Extraction of Pb(II) Ions Using an Ion-Imprinted Functionalized Sodium Trititanate Whisker Adsorbent Prepared by a Surface-Imprinting Technique
Authors: Xu Wanzhen , Yang Wenming , Zhou Wei 
Published: March 2011

Lead(II) ion-imprinted functionalized sodium trititanate whisker polymers [Pb(II)-IIPs/Na2Ti3O7] for solid-phase extraction (SPE) were prepared by the copolymerization of Pb(II) as the template ion, chitosan (CTS) as the functional monomer and γ-glycidoxypropyl trimethoxysilane (KH-560) as the linking agent in the presence of sodium trititanate whiskers (Na2Ti3O7) as the carrier. The Pb(II)-IIPs/Na2Ti3O7 materials capable of selectively adsorbing Pb(II) ions thus obtained were used for the pre-concentration and determination of the Pb(II) ion concentration in Chinese traditional medicine samples. The prepared sorbent was characterized by Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). A series of batch adsorption experiments was performed to evaluate the adsorption behaviour of the Pb(II)-IIPs/Na2Ti3O7 materials towards Pb(II) ions, as assessed by inductively coupled plasma–atomic emission spectrometry (ICP–AES). The maximum adsorption capacity, the distribution coefficient (Kd) and the relative selectivity coefficients (k′) of Pb(II)-IIPs for Pb(II)/Co(II), Pb(II)/Cd(II), Pb(II)/Cu(II), Pb(II)/Hg(II), Pb(II)/Mg(II), Pb(II)/Mn(II), Pb(II)/Zn(II) and Pb(II)/Ni(II) were calculated. Compared with non-ionimprinted polymers functionalized sodium trititanate whisker polymers (non-IIPs/Na2Ti3O7), the Pb(II)-IIPs/Na2Ti3O7 material had a higher selectivity towards Pb(II) ions. The relative selectivity factor (k′) values were all greater than 2.5. The developed method was successfully applied to the determination of the amounts of trace Pb(II) ions in traditional Chinese medicine samples with satisfactory results.
Effects of Ozone Dissolved in Water on the Physicochemical Properties of Activated Carbons Applied in Drinking Water Treatment
Authors: Biniak Stanisław , Trykowski Grzegorz , Pakuła Maciej , Świątkowski Andrzej , Malinowska Zofia , Popiel Stanisław 
Published: March 2011

The results of treating commercial granulated activated carbons with ozone, both gaseous and dissolved in water, were analyzed. The original carbons (Filtrasorb-300 and Carbsorb-38) were carefully flushed with distilled water to remove any water-soluble impurities. For comparison, each of the washed activated carbons was treated separately with aqueous hydrogen peroxide. The following procedures were applied to assess the effects of contact between each carbon and the oxidizing agents: thermogravimetry, alkalimetry, voltammetry, EDX and FT-IR methods to illustrate changes in the surface chemistry, and nitrogen low-temperature adsorption to show up any possible changes in the porous structure. Ozone dissolved in water exhibited the lowest oxidative strength — EDX and FT-IR spectroscopy revealed only a slight oxidation of the Filtrasorb-300 surface layer. Despite its smaller specific area, this carbon surface exhibited greater roughness and was more susceptible to oxidation. The liquid-phase adsorption isotherms of p-chlorophenol from aqueous solution onto this carbon showed that surface oxygen reduced the extent of adsorption. The experimental data were best fitted by the Langmuir isotherm model.
Point-of-Care Testing for Hb A1c in the Management of Diabetes: A Systematic Review and Metaanalysis
Authors: Al-Ansary Lubna , Farmer Andrew , Hirst Jennifer , Roberts Nia , Glasziou Paul , Perera Rafael , Price Christopher P 
Published: March 2011

BACKGROUND
The measurement of hemoglobin A1c (Hb A1c) is employed in monitoring of patients with diabetes. Use of point-of-care testing (POCT) for Hb A1c results at the time of the patient consultation potentially provides an opportunity for greater interaction between patient and caregiver, and more effective care.

OBJECTIVE
To perform a systematic review of current trials to determine whether POCT for Hb A1c, compared with conventional laboratory testing, improves outcomes for patients with diabetes.

METHODS
Searches were undertaken on 4 electronic databases and bibliographies from, and hand searches of, relevant journal papers. Only randomized controlled trials were included. The primary outcome measures were change in Hb A1c and treatment intensification. Metaanalyses were performed on the data obtained.

RESULTS
Seven trials were found. There was a nonsignificant reduction of 0.09% (95% CI −0.21 to 0.02) in the Hb A1c in the POCT compared to the standard group. Although data were collected on the change in proportion of patients reaching a target Hb A1c of &lt;7.0%, treatment intensification and heterogeneity in the populations studied and how measures were reported precluded pooling of data and metaanalysis. Positive patient satisfaction was also reported in the studies, as well as limited assessments of costs.

CONCLUSIONS
There is an absence of evidence in clinical trial data to date for the effectiveness of POCT for Hb A1c in the management of diabetes. In future studies attention to trial design is needed to ensure appropriate selection and stratification of patients, collection of outcome measures, and action taken upon Hb A1c results when produced.
Sensitivity and specificity of the high fluorescent lymphocyte count-gate on the Sysmex XE-5000 hematology analyzer for detection of peripheral plasma cells
Authors: van Mirre Edwin , Vrielink Gert Jan , Tjon-a-Tsoi Nicole , Hendriks Henriët , de Kieviet Wim , ten Boekel Edwin 
Published: March 2011

Abstract

Background: Plasma cells are one of the end products of the B-lymphocyte mediated immune response. These cells normally reside in the bone marrow or some peripheral lymphoid tissues. Increased numbers of plasma cells in the blood, usually indicates pathology such as infection, auto-immunity or haematological malignancy. Therefore, the ability to measure plasma cells (PCs) on an automated cell analyzer might be advantageous.

Methods: The performance of the Sysmex XE-5000 leukocyte differential channel [high fluorescent lymphocyte count (HFLC) area] was evaluated for the ability to detect plasma cells in peripheral blood and compared to the detection of plasma cells by flow cytometric analyses.

Results: Our results show that the HFL count from the XE-5000 correlates (R2=0.8) with the number of PCs in peripheral blood, but detects PCs with moderate to good sensitivity (88.9%) and specificity (87.8%).

Conclusions: The Sysmex XE-5000 is suitable for screening blood samples for the presence of elevated number of plasma cells in peripheral blood, but the actual quantification needs to be confirmed by flow cytometry.
Performance evaluation of a multiplex assay for future use in biomarker discovery efforts to predict body composition
Authors: Bea Jennifer W. , Wright Nicole C. , Thompson Patricia , Hu Chengcheng , Guerra Stefano , Chen Zhao 
Published: March 2011

Abstract

Background: Interest in biomarker patterns and disease has led to the development of immunoassays that evaluate multiple analytes in parallel while using little sample. However, there are no current standards for multiplex configuration, validation, and quality. Thus, validation by platform, population, and question of interest is recommended. We sought to determine the best blood fraction for multiplex evaluation of circulating biomarkers in post-menopausal women, and to explore body composition phenotype discrimination by biomarkers.

Methods: Archived serum and plasma samples from a sample of healthy post-menopausal women with the highest (n=9) and lowest (n=11) percent lean mass, as determined by dual-energy X-ray absorptiometry, were used to measure 90 analytes using bead-based, suspension multiplex assays. Replicates of serum and plasma were analyzed in a random selection of four of these individuals.

Results: Ninety percent of the analytes were detectable for ≥50% of samples; when limited to these well detected analytes, mean replicate correlations for serum and plasma were 0.87 and 0.85, respectively. Serum had lower error rates discriminating phenotypes; seven serum vs. two plasma analytes discriminated extreme body phenotypes.

Conclusions: Serum and plasma performed similarly for the majority of the analytes. Serum showed a slight advantage in predicting extreme body composition phenotypes in postmenopausal women using parallel evaluation of analytes.