bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens
Authors: Dunston C R , Griffiths H R 
Published: July 2010

Summary
The cellular changes during ageing are incompletely understood yet immune system dysfunction is implicated in the age-related decline in health. The acquired immune system shows a functional decline in ability to respond to new pathogens whereas serum levels of cytokines are elevated with age. Despite these age-associated increases in circulating cytokines, the function of aged macrophages is decreased. Pathogen-associated molecular pattern receptors such as Toll-like receptors (TLRs) are vital in the response of macrophages to pathological stimuli. Here we review the evidence for defective TLR signalling in normal ageing. Gene transcription, protein expression and cell surface expression of members of the TLR family of receptors and co-effector molecules do not show a consistent age-dependent change across model systems. However, there is evidence for impaired downstream signalling events, including inhibition of positive and activation of negative modulators of TLR induced signalling events. In this paper we hypothesize that despite a poor inflammatory response via TLR activation, the ineffective clearance of pathogens by macrophages increases the duration of their activation and contributes to perpetuation of inflammatory responses and ageing.
Specific antibodies to soluble alpha-synuclein conformations in intravenous immunoglobulin preparations
Authors: Patrias L M , Klaver A C , Coffey M P , Loeffler D A 
Published: July 2010

Summary
Alpha-synuclein is the major protein in Lewy bodies, the hallmark pathological finding in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although normally intracellular, it also can be secreted, so extracellular alpha-synuclein may contribute to neuronal injury. Serum antibodies to alpha-synuclein could exert protective effects by increasing alpha-synuclein's movement out of the brain and, if they cross the blood–brain barrier, by inhibiting its neurotoxic effects. The objective of this study was to measure antibody concentrations to alpha-synuclein monomer and soluble oligomers in three intravenous immunoglobulin (IVIG) preparations, Gamunex (Talecris Biotherapeutics), Gammagard (Baxter Healthcare) and Flebogamma (Grifols Biologicals). Antibodies were measured in native IVIG preparations and after antibody–antigen complex dissociation. IVIG's non-specific binding was subtracted from its total binding to alpha-synuclein to calculate specific anti-alpha-synuclein antibody concentrations. Specific antibodies to alpha-synuclein monomer and/or soluble oligomers were detected in all IVIG products. In native IVIG preparations, the highest anti-monomer concentrations were in Gammagard and the highest anti-oligomer concentrations were in Gamunex; the extent to which lot-to-lot variation may have contributed to these differences was not determined. Antibody–antigen complex dissociation had variable effects on these antibody levels. The IVIG preparations did not inhibit alpha-synuclein oligomer formation, although they changed the distribution and intensity of some oligomer bands on Western blots. The presence of antibodies to soluble alpha-synuclein conformations in IVIG preparations suggests that their effects should be studied in animal models of synucleinopathies, as a first step to determine their feasibility as a possible treatment for PD and other synucleinopathies.
Peroxiredoxin 2 is a novel autoantigen for anti-endothelial cell antibodies in systemic vasculitis
Authors: Karasawa R , Kurokawa M S , Yudoh K , Masuko K , Ozaki S , Kato T 
Published: July 2010

Summary
Anti-endothelial cell antibodies (AECA) have been frequently detected in systemic vasculitis, which affects blood vessels of various sizes. To understand the pathogenic roles of AECA in systemic vasculitis, we attempted to identify target antigens for AECA comprehensively by a proteomic approach. Proteins extracted from human umbilical vein endothelial cells (HUVEC) were separated by two-dimensional electrophoresis, and Western blotting was subsequently conducted using sera from patients with systemic vasculitis. As a result, 53 autoantigenic protein spots for AECA were detected, nine of which were identified by mass spectrometry. One of the identified proteins was peroxiredoxin 2 (Prx2), an anti-oxidant enzyme. Frequency of anti-Prx2 autoantibodies, measured by enzyme-linked immunosorbent assay (ELISA), was significantly higher in systemic vasculitis (60%) compared to those in collagen diseases without clinical vasculitis (7%, P &lt; 0·01) and healthy individuals (0%, P &lt; 0·01). Further, the titres changed in parallel with the disease activity during time–courses. The presence of anti-Prx2 autoantibodies correlated significantly with elevation of serum d-dimers and thrombin–antithrombin complex (P &lt; 0·05). Immunocytochemical analysis revealed that live endothelial cells expressed Prx2 on their surface. Interestingly, stimulation of HUVEC with rabbit anti-Prx2 antibodies increased secretion of interleukin (IL)-6, IL-1β, IL-1ra, growth regulated oncogene (GRO)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM–CSF), IL-8 and monocyte chemoattractant protein (MCP)-1 more than twofold compared to that of with rabbit immunoglobulin (Ig)G. Taken together, our data suggest that anti-Prx2 autoantibodies would be a useful marker for systemic vasculitis and would be involved in the inflammatory processes of systemic vasculitis.
Critical thinking skills in nursing students: comparison of simulation‐based performance with metrics
Authors: Fero Laura J. , O’Donnell John M. , Zullo Thomas G. , Dabbs Annette DeVito , Kitutu Julius , Samosky Joseph T. , Hoffman Leslie A. 
Published: July 2010

fero l.j., o’donnell j.m., zullo t.g., dabbs a.d., kitutu j., samosky j.t. & hoffman l.a. (2010) Critical thinking skills in nursing students: comparison of simulation‐based performance with metrics. Journal of Advanced Nursing 66(10), 2182–2193.AbstractAim  This paper is a report of an examination of the relationship between metrics of critical thinking skills and performance in simulated clinical scenarios.Background  Paper and pencil assessments are commonly used to assess critical thinking but may not reflect simulated performance.Methods  In 2007, a convenience sample of 36 nursing students participated in measurement of critical thinking skills and simulation‐based performance using videotaped vignettes, high‐fidelity human simulation, the California Critical Thinking Disposition Inventory and California Critical Thinking Skills Test. Simulation‐based performance was rated as ‘meeting’ or ‘not meeting’ overall expectations. Test scores were categorized as strong, average, or weak.Results  Most (75·0%) students did not meet overall performance expectations using videotaped vignettes or high‐fidelity human simulation; most difficulty related to problem recognition and reporting findings to the physician. There was no difference between overall performance based on method of assessment (P = 0·277). More students met subcategory expectations for initiating nursing interventions (P ≤ 0·001) using high‐fidelity human simulation. The relationship between videotaped vignette performance and critical thinking disposition or skills scores was not statistically significant, except for problem recognition and overall critical thinking skills scores (Cramer’s V = 0·444, P = 0·029). There was a statistically significant relationship between overall high‐fidelity human simulation performance and overall critical thinking disposition scores (Cramer’s V = 0·413, P = 0·047).Conclusion  Students’ performance reflected difficulty meeting expectations in simulated clinical scenarios. High‐fidelity human simulation performance appeared to approximate scores on metrics of critical thinking best. Further research is needed to determine if simulation‐based performance correlates with critical thinking skills in the clinical setting.
Individual variation in rates of senescence: natal origin effects and disposable soma in a wild bird population
Authors: Bouwhuis Sandra , Charmantier Anne , Verhulst Simon , Sheldon Ben C. 
Published: July 2010

Summary 1. Longitudinal studies of various vertebrate populations have recently demonstrated senescent declines in reproductive performance and/or survival probability with age to be almost ubiquitous in nature. Little is known, however, about the extent to which rates of senescence vary between individuals, and about causes or consequences of such variation. Quantifying these links in natural populations is important for understanding the constraints and adaptive processes underlying the evolution of senescence. 2. Here, we analyse breeding data from 1029 female great tits Parus major to quantify the effect of natal conditions and early life reproduction on rates of reproductive senescence, reproductive life span and lifetime reproductive success. 3. Although for locally born females we find no evidence that natal conditions influence rates of reproductive senescence, we show that immigrant females suffer from faster rates of senescence than locally born females, and that this difference contributes to immigrants having a lower lifetime reproductive success. 4. Additionally, and independently, we find rates of reproductive senescence to increase with rates of early life reproduction, as predicted by the disposable soma hypothesis. Despite accelerated senescence late in life, high early life reproduction is, however, positively associated with lifetime reproductive success across individuals. 5. Female immigrant status and early life reproduction do not relate to reproductive life span. 6. We thus show that both immigration into our population, and high levels of early life reproduction, are associated with reduced late life reproductive performance in female great tits, but that fitness can be increased by high levels of early life reproduction at the expense of accelerated reproductive senescence. These results suggest disposable soma to be a likely mechanism underlying senescence in these birds, and encourage further study of the genetic basis (i.e. antagonistic pleiotropy) of such an early vs. late life trade‐off.
Pharmacovigilance in veterinary medicine in Chile: a pilot study
Authors: IRAGÜEN D. , URCELAY S. , SAN MARTÍN B. 
Published: July 2010

Iragüen, D., Urcelay, S., San Martín, B. Pharmacovigilance in veterinary medicine in Chile: a pilot study.J. vet. Pharmacol. Therap.34, 108–115.In Chile, there is no present government policy to survey and analyse adverse drug reactions (ADRs) in the field of veterinary medicine. The intent of this study is to assess, for the first time, ADR frequency in treated animals. To this purpose, a 6‐month period pilot study based on WHO recommendations was conducted to monitor ADRs in cats and dogs for frequently used drugs and common labelled signs. Of a total of 149 detected ADRs, 29 (6 in cats and 23 in dogs) were notified by means of ADR report forms, while the rest was identified after reviewing patient clinical records, thus evidencing strong under‐reporting problems. More than 70% of ADRs were related to antimicrobials, vaccines and tranquilizers. In dogs, there was a significant effect on ADRs’ presentation when acepromazine, amoxicillin, carprofen, ivermectin, sextuple vaccine (polyvalent vaccine that confers immunity against canine distemper virus, canine parvovirus,Leptospira canicola, L. icterohemmoragiae, canine adenovirus type 2 and canine parainfluenza virus) and phytomenadione (subcutaneous injection) were administered. In the case of cats, a significant influence on ADRs was detected when acepromazine, amoxicillin or vitamin K was administered. Present results suggest the need for a pharmacovigilance programme in veterinary medicine for timely ADR‐presenting drug detection and drug safety improvement.
Depletion study of three formulations of flumequine in edible tissues and drug transfer into chicken feathers
Authors: CORNEJO J. , LAPIERRE L. , IRAGÜEN D. , PIZARRO N. , HIDALGO H. , MARTÍN B. SAN 
Published: July 2010

Cornejo, J., Lapierre, L., Iragüen, D., Pizarro, N., Hidalgo, H., San Martín, B. Depletion study of three formulations of flumequine in edible tissues and drug transfer into chicken feathers.J. vet. Pharmacol. Therap.34, 168–175.To ensure the delivery of safe animal products to consumers, withdrawal times (WDT) of drugs must be respected. Drugs administered in therapies can also reach nonedible tissues (for humans) such as feathers; this transfer is of concern as feather meal is used in diets of food producing animals, being this a possible source of residue contamination of final products for human consumption. WDTs of three flumequine formulations (10%, 80% premix powder and 20% solution) as well as the transfer of this drug into feathers were determined. One hundred and twenty broiler chickens were allocated into four experimental groups (36 birds each). Three of them were treated with 24 mg/kg bw orally for five consecutive days of each flumequine formulation, whereas one group remained untreated (12 birds as control group). After the treatment ended, six chickens of each experimental group and two controls were slaughtered daily for 6 days. Samples of muscle, liver and feathers were collected and analyzed by liquid chromatography tandem mass spectrometry (LC MS/MS). The WDTs showed differences between formulations. Flumequine concentrations found in feathers remained high during WDT and after this period, thus suggesting that the WDTs estimated for the pharmaceutical formulation of flumequine do not guarantee the absence of this drug in chicken nonedible tissues such as feathers.
Ultrasound‐guided peripheral nerve blocks: What are the benefits?
Authors: KOSCIELNIAK‐NIELSEN Z. J. 
Published: July 2010

Background: Use of ultrasound by anaesthesiologists performing regional blocks is rapidly gaining popularity. The aims of this review were to summarize and update accumulating evidence on ultrasound‐guided nerve blocks, with an emphasis on the clinical relevance of the results and to critically appraise changing standards in regional anaesthesia.Methods: A search of MEDLINE and EMBASE (1966 to 31 December 2007) was conducted using the following free terms: ‘ultrasound and regional anesthesia’, ‘ultrasound and peripheral block’ and ‘ultrasound and nerve and block’. These were combined with the MESH terms ‘nerve block’ and ‘ultrasonography’. The following limits were applied: studies with abstracts, only in humans, published in core clinical journals. Trial type: meta‐analysis, randomized‐controlled trial and clinical trial.Results: When peripheral nerves are adequately imaged by ultrasound, the concomitant use of nerve stimulation offers no further advantage. However, several studies reported problems with obtaining satisfactory images in some patients. Ultrasound guidance significantly shortened the block performance time and/or reduced the number of needle passes to reach the target in all comparative studies. The occurrence of paraesthesia during block performance was also reduced, but not the incidence of short‐lasting post‐operative neuropraxia. The frequency of accidental vascular punctures may be lower, but the data are contradictory. Block onset time was significantly shortened. Block duration was longer in children, but not in adults. Ultrasound also allowed dose reduction of the local anaesthetic (LA).Conclusions: Ultrasound guidance shortens the block performance time, reduces the number of needle passes and shortens the block onset time. Blocks may be performed using lower LA doses.
Characterisation of seeds of a C4 phosphoenolpyruvate carboxylase‐deficient mutant of Amaranthus edulis
Authors: Álvarez R. , Gandullo J. , Feria A. B. , Dever L. V. , Vidal J. , Echevarría C. 
Published: July 2010

AbstractSeeds from the C4 plant Amaranthus edulis were studied as part of the characterisation of a mutant (designated LaC4 2.16), which contains reduced amounts (5% of wild type) of the photosynthetic leaf form of phosphoenolpyruvate carboxylase (PEPC). On a per seed basis, the amount of PEPC activity was not significantly altered, while the weight and protein content of the mutant seeds were 34% lower than that of the wild type. Western gel blot analysis detected two PEPC polypeptides with molecular masses of 105 kDa (minor) and 100 kDa (major). The determination of in vitro phosphorylation in reconstituted assays revealed the presence of both calcium‐dependent and calcium‐independent PEPC‐kinase activities in protein extracts of wild‐type and mutant seeds. However, PEPC proteins were phosphorylated in dry seeds, and PEPC phosphorylation did not occur in vivo during seed imbibition in the presence of 32P‐phosphate. In contrast, 32P‐phosphate was incorporated into a range of proteins in wild‐type seeds, but not in mutant seeds. In addition, ATP content was much reduced in germinating mutant seeds and this did not increase following the supply of phosphate. Collectively, these data suggest that the deficiency in C4 PEPC in mutant A. edulis leaves has no effect on C3‐type PEPC content and phosphorylation state in seeds, but causes impairment of energy production, thereby accounting for the reduced germination of the mutant.
Identification and characterisation of human pathogenic filamentous fungi and susceptibility to Thymus schimperi essential oil
Authors: Pagiotti Rita , Angelini Paola , Rubini Andrea , Tirillini Bruno , Granetti Bruno , Venanzoni Roberto 
Published: July 2010

SummaryTwenty‐eight clinical fungal isolates were characterised by morphological (macro‐ and micro‐features and growth response at 25, 30 and 37 °C) and molecular (nuclear rDNA‐internal transcriber spacer, calmodulin, cytochrome c oxidase 1 and the largest subunit of RNA polymerase II) analyses. The clinical fungal isolates were ascribed to the following taxa: Penicillium chrysogenum, Verticillium sp., Aspergillus tubingensis, Aspergillus minutus, Beauveria bassiana and Microsporum gypseum. In addition, in vitro susceptibility testing of the isolates to conventional antifungal agents and to two chemically well‐defined chemotypes of Thymus schimperi essential oil was performed. Most of the isolates were resistant to amphotericin B (except A. minutus), and itraconazole, while terbinafine was quite active on these fungi. T. schimperi essential oil showed antifungal activity against all of the tested fungal isolates with minimal inhibitory concentration values similar or lower than those of terbinafine. Transmission electron microscopy analyses revealed that fungal growth inhibition by essential oil was accompanied by marked morphological and cytological changes.
Risk factors in a cohort of patients with multiple primary melanoma
Authors: McMeniman Erin , De'Ambrosis Kathryn , De'Ambrosis Brian 
Published: July 2010

ABSTRACTBackground: There are various known familial and environmental risk factors that influence the risk for melanoma. This study sought to define the risk factors for multiple primary melanoma.Methods: A telephone survey of patients with multiple primary melanomas was conducted from a private practice in south‐east Queensland, in order to examine various risk factors in this cohort.Results: Our findings of high rates of family history of melanoma (37%), and of dysplastic naevi (42%) support the influence of genotype in this high‐risk group. A family history of multiple primary melanomas, seen in 17% of our patients, is a risk factor not previously reported in similar cohort studies. Sixty‐eight per cent of patients had an equal or lesser degree of invasive malignancy in subsequent melanomas. Most multiple primary melanoma patients in this group (86.6%) were conducting self skin examination at least once per month. With regards to sun‐protective behaviour, 85% reported regular sunscreen use and 92% reported regular use of sun‐protective clothing; however, fewer had done this in childhood.Conclusions: Enhanced knowledge of the genetic and environmental risk factors for multiple primary melanomas can assist clinicians in assessing risk and planning surveillance of patients.
Role of echocardiographic left ventricular mass and carotid intima‐media thickness in the cardiovascular risk assessment of asymptomatic patients with type 2 diabetes mellitus
Authors: Poppe K. K. , Whalley G. A. , Somaratne J. B. , Keelan S. , Bagg W. , Triggs C. M. , Doughty R. N. 
Published: July 2010

AbstractBackground: Standard cardiovascular (CV) risk assessment may underestimate risk in people with type 2 diabetes mellitus (T2DM). Cardiac and vascular imaging to detect subclinical disease may augment risk prediction. This study investigated the association between CV risk, left ventricular hypertrophy (LVH) and carotid intima‐media thickness (CIMT) in patients with T2DM free of CV symptoms.Methods: People with T2DM without known CV disease were recruited from general practice. The 5‐year risk of CV events was calculated using an adjusted Framingham equation and the prevalence of LVH and abnormal CIMT across bands of CV risk assessed. In those at intermediate risk, the number needed to scan (NNS) to reclassify one person to high risk was calculated across the group and compared in those above and below 55 years. The association between LV mass and CIMT was also assessed.Results: Mean age 57 years (SD11), 51% female. Median 5‐year CV risk 14.3% (interquartile range 10.3, 19.5), 51% had LVH (American Society of Echocardiography criteria) and 31% an abnormal CIMT (age and sex criteria). In the 52% at intermediate risk, 37% had LVH and 36% an abnormal CIMT. The NNS was 1.7 using both imaging techniques, 2.7 using cardiac imaging alone or 2.8 using vascular imaging alone. Almost twice as many people >55 years had an abnormal CIMT than those <55 years.Conclusions: Cardiac and vascular imaging to detect subclinical disease can be used to augment prediction of CV risk in people with T2DM at intermediate risk. The value of reclassifying risk is as yet unproven and requires outcome data from intervention studies.