bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low glomerular filtration rate is a risk factor for ribavirin‐associated anaemia in old patients with chronic hepatitis C
Authors: Borroni G. , Cazzaniga M. , Andreoletti M. , Ceriani R. , Guerzoni P. , Omazzi B. , Pich M. G. L. , Prada A. , Spinzi G. , Terreni N. , Salerno F. 
Published: October 2012

SummaryElderly patients with chronic hepatitis C have a reduced responsiveness to antiviral therapy with Peg‐interferon and ribavirin. The dose reduction or the discontinuation of ribavirin due to the occurrence of anaemia is one of the most important causes for the low sustained viral response observed in older patients. We aimed to evaluate the relationship between baseline renal function and the early onset of ribavirin‐associated anaemia in older (≥60 years) patients. Using data from 348 patients with chronic hepatitis C consecutively treated with peg‐interferon plus ribavirin, we investigated which factors were associated with the occurrence of anaemia in elderly patients (≥60 years). Ribavirin‐induced anaemia occurred in 40.5% of patients. Older patients showed a rate of anaemia significantly higher than younger patients (51.5% vs 36.3%; P = 0.009). Consequently, the rate of ribavirin dose reduction or discontinuation due to anaemia was 35.1% in older patients and 23.5% in younger patients (P = 0.029). A significantly higher proportion of older patients had a low baseline glomerular filtration rate (GFR) compared with younger patients (56.7% vs 27.1%; P < 0.001). At the multivariate regression analysis, low baseline GFR (<70 mL/min) was associated with an increased risk of ribavirin‐associated anaemia only in the older patients (OR: 3.526; 95% CI: 1.385–8.979; P = 0.008). In this subset, baseline GFR was significantly correlated with both absolute (r = −0.320; P < 0.001) and relative (r = −0.324; P < 0.001) haemoglobin decrease within the first 8 weeks of treatment. In patients aged >60 years, a low pre‐treatment GFR was strongly associated with the risk to develop ribavirin‐related anaemia with consequent reduction in ribavirin doses.
Assessment of Sperm Function Parameters and DNA Fragmentation in Ejaculated Alpaca Sperm (Lama Pacos) by Flow Cytometry
Authors: Cheuquemán C , Merino O , Giojalas L , Von Baer A , Sánchez R , Risopatrón J 
Published: October 2012

ContentsFlow cytometry has been shown to be an accurate and highly reproducible tool for the analysis of sperm function. The main objective of this study was to assess sperm function parameters in ejaculated alpaca sperm by flow cytometry. Semen samples were collected from six alpaca males and processed for flow cytometric analysis of sperm viability and plasma membrane integrity using SYBR‐14⁄PI staining; acrosomal membrane integrity using FITC‐conjugated Pisum Sativum Agglutinin⁄PI labelling; mitochondrial membrane potential (Δψm) by staining with JC‐1 and DNA Fragmentation Index (DFI) by TUNEL. The results indicate that the mean value for sperm viability was 57 ± 8 %. Spermatozoa with intact acrosome membrane was 87.9 ± 5%, and viable sperm with intact acrosomal membrane was 46.8 ± 9%, high mitochondrial membrane potential (Δψm) was detected in 66.32 ± 9.51% of spermatozoa and mean DFI value was 0.91 ± 0.9%. The DFI was inversely correlated with high Δψm (p = 0.04; r = −0.41) and with plasma membrane integrity (p = 0.01; r = −0.47). To our knowledge, this is the first report of the assessment on the same sample of several parameters of sperm function in ejaculated alpaca sperm by flow cytometry.
The combined use of photoaffinity labeling and surface plasmon resonance‐based technology identifies multiple salicylic acid‐binding proteins
Authors: Tian Miaoying , von Dahl Caroline C. , Liu Po‐Pu , Friso Giulia , van Wijk Klaas J. , Klessig Daniel F. 
Published: October 2012

SummarySalicylic acid (SA) is a small phenolic molecule that not only is the active ingredient in the multi‐functional drug aspirin, but also serves as a plant hormone that affects diverse processes during growth, development, responses to abiotic stresses and disease resistance. Although a number of SA‐binding proteins (SABPs) have been identified, the underlying mechanisms of action of SA remain largely unknown. Efforts to identify additional SA targets, and thereby elucidate the complex SA signaling network in plants, have been hindered by the lack of effective approaches. Here, we report two sensitive approaches that utilize SA analogs in conjunction with either a photoaffinity labeling technique or surface plasmon resonance‐based technology to identify and evaluate candidate SABPs from Arabidopsis. Using these approaches, multiple proteins, including the E2 subunit of α‐ketoglutarate dehydrogenase and the glutathione S‐transferases GSTF2, GSTF8, GSTF10 and GSTF11, were identified as SABPs. Their association with SA was further substantiated by the ability of SA to inhibit their enzymatic activity. The photoaffinity labeling and surface plasmon resonance‐based approaches appear to be more sensitive than the traditional approach for identifying plant SABPs using size‐exclusion chromatography with radiolabeled SA, as these proteins exhibited little to no SA‐binding activity in such an assay. The development of these approaches therefore complements conventional techniques and helps dissect the SA signaling network in plants, and may also help elucidate the mechanisms through which SA acts as a multi‐functional drug in mammalian systems.
Tree size affects accumulation of carbon and nitrogen metabolites in white spruce seedlings during short day-induced bud formation
Authors: Dhont Catherine , Bertrand Annick , Castonguay Yves , Cooke Janice E.K. , Isabel Nathalie 
Published: October 2012

The present study documents the changes in carbon and nitrogen metabolites occurring in apical buds and previous year stems of white spruce seedlings ( Picea glauca [Moench] Voss) with contrasting growth phenotypes (tall vs. small) after transfer to short day (SD; 8 h) photoperiod to induce bud formation. Concentrations of total nonstructural carbohydrates markedly increased in the developing buds within the days after transfer to SD, mainly as a result of increased concentrations of monosaccharides such as glucose, fructose, and pinitol. At the same time, starch levels declined, with the resulting carbohydrates presumably used to meet early carbon requirements of the SD-induced apical bud. Concentrations of glutamine, glutamic acid and proline also decreased immediately after transfer to SD in both organs. Later stages of SD-induced bud formation were characterized by an increase in starch, sucrose, and glutamine concentrations in previous year stems, concomitant with an increase in the steady-state levels of UDP-glucose pyrophosphorylase and glutamine synthetase protein. In contrast, arginine levels increased after 2 weeks of SD exposure, indicating a transition in arginine metabolism at the time of initiation of shoot stem primordia and bud elongation. Higher accumulation of total nonstructural carbohydrates and total amino acids in previous year stems of small trees could indicate lower sink strength of apical bud during its development, which could in turn impact subsequent tree growth.
The effect of endogenous estrogen on Doppler-estimated right ventricular systolic pressure during exercise
Authors: Wang Vicki N. , Ahmed Mavra , Ciofani Amelia , Sasson Zion , Granton John T. , Mak Susanna 
Published: October 2012

We evaluated the effect of endogenous estrogen levels on exercise-related changes in right ventricular systolic pressure (RVSP) of healthy, eumenorrheic, sedentary women. Volunteers were studied at two separates phases of the menstrual cycle (LO and HI estrogen phases), exercised on a semi-supine ergometer with escalating workload and monitored continuously by 12-lead ECG and automated blood pressure cuff. At each exercise stage, Doppler echocardiography measurements were obtained and analyzed to determine RVSP. Fourteen subjects (age 24 ± 5) were studied. Exercise duration was significantly higher on the HI estrogen day, but no significant differences in hemodynamic response to exercise were found between the two study days. There were also no significant differences with respect to heart rate (HR) acceleration during early exercise, as well as resting and peak RVSP, HR, blood pressure, and rate pressure product. Doppler-estimated RVSP demonstrated a linear relationship to HR at a ratio of 1 mm Hg (1 mm Hg = 133.3224 Pa) for every 5 bpm (beats per minute) increase in HR. There were no differences in the slope of this relationship between HI and LO estrogen phases of the menstrual cycle. Our findings did not demonstrate any effect of endogenous estrogen levels on the modulation of the pulmonary vascular response to exercise in healthy women.
Preventive and therapeutic effects of quercetin on lipopolysaccharide-induced oxidative stress and vascular dysfunction in mice
Authors: Kukongviriyapan Upa , Sompamit Kwanjit , Pannangpetch Patchareewan , Kukongviriyapan Veerapol , Donpunha Wanida 
Published: October 2012

Quercetin, a dietary antioxidant flavonoid, possesses strong anti-inflammatory and cytoprotective activities. The effects were investigated in an animal model of lipopolysaccharide (LPS)-induced endotoxaemia and vascular dysfunction in vivo. Male ICR mice were injected with LPS (10 mg/kg; i.p.). Quercetin (50 or 100 mg/kg) was intragastrically administered either before or after LPS administration. Fifteen hours after LPS injection, mice were found in endotoxaemic condition, as manifested by hypotension, tachycardia, and blunted vascular responses to vasodilators and vasoconstrictor. The symptoms were accompanied by increased aortic iNOS protein expression, decreased aortic eNOS protein expression, marked suppression of cellular glutathione (GSH) redox status, enhanced aortic superoxide production, increased plasma malodialdehyde and protein carbonyl, and elevated urinary nitrate/nitrite. Treatment with quercetin either before or after LPS preserved the vascular function, as blood pressure, heart rate, vascular responsiveness were restored to near normal values, particularly when quercetin was given as a preventive regimen. The vascular protective effects were associated with upregulation of eNOS expression, reduction of oxidative stress, and maintained blood GSH redox ratio. Overall findings suggest the beneficial effect of quercetin on the prevention and restoration of a failing eNOS system and alleviation of oxidative stress and vascular dysfunction against endotoxin-induced shock in mice.
Angiotensin II promotes iron accumulation and depresses PGI2and NO synthesis in endothelial cells: effects of losartan and propranolol analogs
Authors: Mak I. Tong , Landgraf Kenneth M. , Chmielinska Joanna J. , Weglicki William B. 
Published: October 2012

Angiotensin may promote endothelial dysfunction through iron accumulation. To research this, bovine endothelial cells (ECs) were incubated with iron (30 µmol·L–1) with or without angiotensin II (100 nmol·L–1). After incubation for 6 h, it was observed that the addition of angiotensin enhanced EC iron accumulation by 5.1-fold compared with a 1.8-fold increase for cells incubated with iron only. This enhanced iron uptake was attenuated by losartan (100 nmol·L–1), d-propranolol (10 µmol·L–1), 4-HO-propranolol (5 µmol·L–1), and methylamine, but not by vitamin E or atenolol. After 6 h of incubation, angiotensin plus iron provoked intracellular oxidant formation (2′7′-dichlorofluorescein diacetate (DCF-DA) fluorescence) and elevated oxidized glutathione; significant loss of cell viability occurred at 48 h. Stimulated prostacyclin release decreased by 38% (6 h) and NO synthesis was reduced by 41% (24 h). Both oxidative events and functional impairment were substantially attenuated by losartan or d-propranolol. It is concluded that angiotensin promoted non-transferrin-bound iron uptake via AT-1 receptor activation, leading to EC oxidative functional impairment. The protective effects of d-propranolol and 4-HO-propranolol may be related to their lysosomotropic properties.
Trends in Antihypertensive Medication Use and Blood Pressure Control Among United States Adults With Hypertension
Authors: Gu Qiuping , Burt Vicki L. , Dillon Charles F. , Yoon Sarah 
Published: October 2012

Background—
The monitoring of national trends in hypertension treatment and control can provide important insight into the effectiveness of primary prevention efforts for cardiovascular disease. The objective of this study was to examine recent trends in antihypertensive medication use and its impact on blood pressure control among US adults with hypertension.

Methods and Results—

A total of 9320 hypertensive people aged ≥18 years from the National Health and Nutrition Examination Survey 2001 to 2010 were included in this study. The prevalence of antihypertensive medication use increased from 63.5% in 2001 to 2002 to 77.3% in 2009 to 2010 (
P
trend
<0.01). Most notably, there was a large increase in the use of multiple antihypertensive agents (from 36.8% to 47.7%,
P
trend
<0.01). Overall, the use of thiazide diuretics, β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers increased by 23%, 57%, 31%, and 100%, respectively. In comparison with monotherapy, single-pill combinations and multiple-pill combinations were associated with 55% and 26% increased likelihoods of blood pressure control, respectively. By the 2009 to 2010 time period, 47% of all hypertensive people and 60% of treated hypertensive people had blood pressure controlled. However, higher treated but uncontrolled hypertension rates continued to persist among older Americans, non-Hispanic blacks, diabetic people, and those with chronic kidney disease. Also, Mexican Americans with hypertension were still less likely to take antihypertensive medication than non-Hispanic whites with hypertension.

Conclusions—
Antihypertensive medication use and blood pressure control among US adults with hypertension significantly increased over the past 10 years. Combination therapy regimens can facilitate achievement of blood pressure goals.
Assessment of Cortical Hemodynamics by Multichannel Near-Infrared Spectroscopy in Steno-Occlusive Disease of the Middle Cerebral Artery
Authors: Oldag Andreas , Goertler Michael , Bertz Anne-Katrin , Schreiber Stefanie , Stoppel Christian , Heinze Hans-Jochen , Kopitzki Klaus 
Published: October 2012

Background and Purpose—
In a pilot study we evaluated near-infrared spectroscopy as to its potential benefit in monitoring patients with steno-occlusive disease of a major cerebral artery for alterations in cortical hemodynamics.

Methods—
Cortical maps of time-to-peak (TTP) in 10 patients unilaterally affected by severe stenosis or occlusion of the middle cerebral artery were acquired by multichannel near-infrared spectroscopy after bolus application of indocyanine green. Hemodynamic manifestations were assessed by comparison between affected and unaffected hemisphere and evaluated for common constituents by principal component analysis. In one patient, TTP values were compared with those obtained by dynamic susceptibility contrast imaging.

Results—

TTP was increased on the affected hemisphere in 9 patients. Mean difference in TTP between hemispheres was 0.44 second (
P
<0.05) as compared with a mean lateral difference of 0.12 second found in a control group of 10 individuals. In group analysis a significant rise in TTP was found in the distribution of the affected middle cerebral artery, whereas principal component analysis suggests augmentation of hemodynamic effects toward the border zones as a dominant pattern. A linear correlation of 0.61 between TTP values determined by dynamic susceptibility contrast MRI and near-infrared spectroscopy was found to be statistically significant (
P
<0.001).

Conclusion—
Multichannel near-infrared spectroscopy might facilitate detection of disease-related hemodynamic changes as yet only accessible by tomographic imaging modalities. Being indicative for hypoperfusion and collateral flow increased values of TTP, as found to a varying extent in the present patient group, might be of clinical relevance.
Detecting transcription of ribosomal protein pseudogenes in diverse human tissues from RNA-seq data
Authors: Tonner Peter , Srinivasasainagendra Vinodh , Zhang Shaojie , Zhi Degui 
Published: October 2012

Abstract

Background
Ribosomal proteins (RPs) have about 2000 pseudogenes in the human genome. While anecdotal reports for RP pseudogene transcription exists, it is unclear to what extent these pseudogenes are transcribed. The RP pseudogene transcription is difficult to identify in microarrays due to potential cross-hybridization between transcripts from the parent genes and pseudogenes. Recently, transcriptome sequencing (RNA-seq) provides an opportunity to ascertain the transcription of pseudogenes. A challenge for pseudogene expression discovery in RNA-seq data lies in the difficulty to uniquely identify reads mapped to pseudogene regions, which are typically also similar to the parent genes.

Results
Here we developed a specialized pipeline for pseudogene transcription discovery. We first construct a “composite genome” that includes the entire human genome sequence as well as mRNA sequences of real ribosomal protein genes. We then map all sequence reads to the composite genome, and only exact matches were retained. Moreover, we restrict our analysis to strictly defined mappable regions and calculate the RPKM values as measurement of pseudogene transcription levels. We report evidences for the transcription of RP pseudogenes in 16 human tissues. By analyzing the Human Body Map 2.0 study RNA-sequencing data using our pipeline, we identified that one ribosomal protein (RP) pseudogene (PGOHUM-249508) is transcribed with RPKM 170 in thyroid. Moreover, three other RP pseudogenes are transcribed with RPKM > 10, a level similar to that of the normal RP genes, in white blood cell, kidney, and testes, respectively. Furthermore, an additional thirteen RP pseudogenes are of RPKM > 5, corresponding to the 20–30 percentile among all genes. Unlike ribosomal protein genes that are constitutively expressed in almost all tissues, RP pseudogenes are differentially expressed, suggesting that they may contribute to tissue-specific biological processes.

Conclusions
Using a specialized bioinformatics method, we identified the transcription of ribosomal protein pseudogenes in human tissues using RNA-seq data.
Molecular characterization of rifampicin-resistant Staphylococcus aureus isolates in a Chinese teaching hospital from Anhui, China
Authors: Zhou Wenjing , Shan Wulin , Ma Xiaoling , Chang Wenjiao , Zhou Xin , Lu Huaiwei , Dai Yuanyuan 
Published: October 2012

Abstract

Background

Staphylococcus aureus (S. aureus) is a major nosocomial pathogen that causes a variety of infections and toxicoses. In recent years, the percentage of rifampicin-resistant S. aureus has increased rapidly in China. The aims of this study were to analyze 1) the level of rifampicin resistance in S. aureus and its correlation with mutations in the rpoB gene, and 2) the molecular characterization of rifampicin-resistant S. aureus isolates.

Results
88 rifampicin-resistant S. aureus isolates were collected for this study. Of the 88 isolates, 83 (94.3%) were high-level rifampicin resistant (MIC≥8 mg/L) while the remaining 5 isolates (5.7%) had a low-level resistance to rifampicin (MIC, 2 to 4 mg/L). Four amino acid substitutions were found in the 88 isolates, which were 481His/Asn (95.5%), 466Leu/Ser (87.5%), 477Ala/Asp (6.8%) and 486Ser/Leu (4.5%) respectively. All mutations were found to be present in cluster I of the rpoB gene. The low-level resistant isolates were found to have only one mutation, while the high-level resistant isolates had at least two or more mutations. The most common multiple mutations were 481His/Asn+466Leu/Ser(92.8%,77/83). The other multiple mutations found were 481His/Asn+477Ala/Asp (6.0%,5/83), and 481His/Asn+466Leu/Ser+477Ala/Asp (1.2%,1/83). Out of 28 high-level rifampicin-resistant S. aureus isolates, three molecular types were found, namely, ST239-MRSA-III-spa t030 (25/28, 89.3%), ST239-MRSA-III-spa t021 (2/28, 7.1%), and ST239-MRSA-III-spa t045 (1/28, 3.6%).

Conclusions
Rifampicin resistance in S. aureus was closely associated with mutations in the rpoB gene. High-level rifampicin-resistant S. aureus is one of the most important features in Anhui Provincial Hospital, and high-level rifampicin resistance in S. aureus is associated with multiple mutations of rpoB gene. The prevalence of high-level rifampicin-resistant S. aureus in Anhui may be associated with the spread of the ST239-MRSA III-spa t030 clone.
Pregnancy and fetal outcomes after Glatiramer Acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study
Authors: Giannini Marta , Portaccio Emilio , Ghezzi Angelo , Hakiki Bahia , Pastò Luisa , Razzolini Lorenzo , Piscolla Elisa , De Giglio Laura , Pozzilli Carlo , Paolicelli Damiano , Trojano Maria , Marrosu Maria Giovanna , Patti Francesco , La Mantia Loredana , Mancardi Gianluigi , Solaro Claudio , Totaro Rocco , Tola Maria Rosaria , De Luca Giovanna , Lugaresi Alessandra , Moiola Lucia , Martinelli Vittorio , Comi Giancarlo , Amato Maria Pia 
Published: October 2012

Abstract

Background
Only few studies have assessed safety of in utero exposure to glatiramer acetate (GA). Following a previous study assessing the safety of interferon beta (IFNB) pregnancy exposure in multiple sclerosis (MS), we aimed to assess pregnancy and fetal outcomes after in utero exposure to GA, using the same dataset, with a specific focus on the risk of spontaneous abortion.

Materials and methods
We recruited MS patients, prospectively followed-up in 21 Italian MS Centres, for whom a pregnancy was recorded in the period 2002–2008. Patients were divided into 2 groups: drug-exposed pregnancies (EP: suspension of the drug less than 4 weeks from conception); non-exposed pregnancies (NEP: suspension of the drug at least 4 weeks from conception or never treated pregnancies). All the patients were administered a structured interview which gathered detailed information on pregnancy course and outcomes, as well as on possible confounders. Multivariate logistic and linear models were used for treatment comparisons.

Results
Data on 423 pregnancies were collected, 17 were classified as EP to GA, 88 as EP to IFNB, 318 as NEP. Pregnancies resulted in 16 live births in the GA EP, 75 live births in the IFNB EP, 295 live births in the NEP. GA exposure was not significantly associated with an increased risk of spontaneous abortion (OR = 0.44;95% CI 0.044-4.51;p = 0.49). Mean birth weight and length were not significantly different in pregnancies exposed to GA than in non exposed pregnancies (p = 0.751). The frequency of preterm delivery, observed in 4 subjects exposed to GA (25% of full term deliveries), was not significantly higher in pregnancies exposed to GA than in those non exposed (p > 0.735). These findings were confirmed in the multivariate analysis. There were neither major complications nor malformations after GA exposure.

Conclusions
Data in our cohort show that mother’s GA exposure is not associated with a higher frequency of spontaneous abortion, neither other negative pregnancy and fetal outcomes. Our findings point to the safety of in utero GA exposure and can support neurologists in the therapeutic counselling of MS women planning a pregnancy.