bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Prostatic evasive anterior tumours’: the role of magnetic resonance imaging
Authors: Lawrentschuk Nathan , Haider Masoom A. , Daljeet Nikhil , Evans Andrew , Toi Ants , Finelli Antonio , Trachtenberg John , Zlotta Alexandre , Fleshner Neil 
Published: October 2009

Study Type – Diagnosis (case series) Level of Evidence 4OBJECTIVETo review our experience and delineate the role of magnetic resonance imaging (MRI) in identifying patients presenting with a raised prostate‐specific antigen (PSA) level and clinical findings suggestive of anterior predominant tumours, which appear to be significant, particularly in those with a previous negative biopsy or low‐volume disease undergoing active surveillance.PATIENTS AND METHODSWe retrospectively reviewed our database to identify patients with anteriorly predominant tumours on MRI whom had undergone prostate biopsy.RESULTSIn all, 31 patients with anterior predominant tumours on MRI also had a positive biopsy (14 on active surveillance and 17 with previous negative biopsies). MRI was usually invoked by the presenting PSA level or PSA velocity. MRI had a positive predictive value for anterior tumours of 87% (27/31). The Gleason score distribution for the 27 men with cancer was 6 in 15; 3 + 4 in three, 4 + 3 in six and 8/9 in three. For prostatic cores, 44/85 (52%) samples from the anterior prostate had cancer. Thirteen patients had a radical prostatectomy (pT2 in three, pT3 in seven and pT4 in three); seven of the 13 had positive surgical margins and a third of them had a biochemical recurrence at the 1‐year follow‐up.CONCLUSIONThere is a subset of patients either having a negative biopsy or low‐volume disease and who are on active surveillance who should be considered for MRI and further biopsy, as their pathology might be aggressive. An entity might be emerging with anterior predominant tumours that are impalpable, and we believe the term ‘prostate evasive anterior tumour syndrome’ to be appropriate. This requires further analysis in a large prospective database with consideration for triggers for MRI and targeted biopsies.
Nerve growth factor and expression of its receptors in patients with diabetic neuropathy
Authors: Kim H. C. , Cho Y. J. , Ahn C. W. , Park K. S. , Kim J. C. , Nam J. S. , Im Y. S. , Lee J. E. , Lee S. C. , Lee H. K. 
Published: October 2009

AbstractAims  Low serum nerve growth factor (NGF) levels have been reported in patients with diabetic peripheral neuropathy (DPN), but the role of NGF in the development of neuropathy is unclear. Thus, we investigated the associations of serum NGF level and NGF receptor activity with the presence and severity of DPN.Methods  One hundred and thirty‐six patients with Type 2 diabetes were included in this cross‐sectional study. Serum NGF levels were measured by ELISA. Expressions of NGF receptors (TrkA and p75NTR) were measured by immunohistochemical staining. The presence and severity of DPN were assessed by neuropathy disability score (NDS) and by corneal nerve fibre length (cNFL) and nerve branch density (cNBD) using in vivo confocal microscopy.Results  Patients with DPN had higher serum NGF levels (56–451 pg/ml) than patients without DPN (4–54 pg/ml). However, in DPN patients, serum NGF was negatively associated with neuropathy severity (mild 222 ± 64 pg/ml; moderate 114 ± 17 pg/ml; severe 89 ± 20 pg/ml). This negative association was consistent in all severity indices (NDS, P < 0.001; cNFL, P < 0.001; cNBD P = 0.010) even after adjustment for age, sex, diabetes duration, insulin use, fasting glucose and glycated haemoglobin. Although NGF receptor activities had significantly (P < 0.05) negative associations with the presence and severity of neuropathy, these associations were not significant when adjusted for other factors.Conclusions  Serum NGF level was positively associated with the presence of DPN but negatively associated with neuropathy severity in DPN patients. The change in serum NGF might be a consequence of, rather than a contributor to, the early development of DPN.
Does an advanced insulin education programme improve outcomes and health service use for people with Type 2 diabetes? A 5‐year follow‐up of the Newcastle Empowerment course
Authors: Lowe J. M. , Mensch M. , McElduff P. , Fitzgerald M. , Attia J. 
Published: October 2009

AbstractObjective  To show that an advanced diabetes education programme delivers sustained benefits to people with diabetes prescribed insulin and healthcare providers over and above those provided by basic diabetes education.Methods  An historical cohort study of 68 people with Type 1 and 51 people with Type 2 diabetes on insulin who attended the 4‐day Newcastle Empowerment programme in 2001 and 2002 compared with 71 people with Type 1 and 312 people with Type 2 diabetes who attended only the basic 4‐day insulin education programme over the same period, followed until 2007. Primary outcome was all hospital admissions and emergency visits; secondary outcomes were the composite of first cardiac event or death and readmission for diabetes complications. Cox‐proportional hazards regression was used to analyse Type 1 and Type 2 diabetes separately.Results  The empowerment programme significantly delayed time to first hospital admission/visit for patients with Type 2 diabetes; the hazard ratio (HR) of 0.41 (P = 0.01) translates into a delay of almost 3 years; this was partly driven by a significant reduction in cardiovascular events and mortality (HR = 0.24, P = 0.01). These effects were not seen for people with Type 1 diabetes.Conclusions  A one‐time, advanced diabetes education programme teaching intensive insulin self‐management with an empowerment style can lead to sustained improvement in patient outcomes and reduce use of hospital services for people with Type 2 diabetes on insulin.
RD Lawrence Lecture 2009 Old genes, new tricks: learning about blood glucose regulation from naturally occurring genetic variation in humans
Authors: Gloyn A. L. 
Published: October 2009

AbstractThe study of rare monogenic forms of diabetes and pancreatic B‐cell dysfunction provides an unrivalled opportunity to link a specific change in gene function with precise cellular consequences and clinical phenotype in humans. Over the past 20 years there has been considerable success in determining the genetic aetiology of a number of rare monogenic forms of diabetes, which has had a significant impact on both our understanding of normal physiology and on translational medicine. The impact of these discoveries has been substantial, with insights into both developmental biology and normal physiology. There are clear examples where determining the genetic aetiology for individuals with rare monogenic subtypes of diabetes has led to improved treatment. Although formerly in the shadow of the monogenic diabetes field, over the past 3 years there has been staggering progress in our understanding of the genetic basis of Type 2 diabetes. This has been largely as a result of genome‐wide association studies and has seen the list of ‘diabetes susceptibility genes’ increase from three to close to 20. There is now encouraging evidence to support a potential role for genetics in determining the response of individuals with Type 2 diabetes to different therapeutic options. One of the challenges that lies ahead is determining how the non‐coding genetic variants exert their pathogenicity. It is possible that parallels can be drawn from functional work on rare regulatory mutations causing monogenic forms of diabetes. However, it is more likely that comprehensive approaches will be necessary.
Mitigating sea turtle by‐catch in coastal passive net fisheries
Authors: Gilman Eric , Gearhart Jeff , Price Blake , Eckert Scott , Milliken Henry , Wang John , Swimmer Yonat , Shiode Daisuke , Abe Osamu , Hoyt Peckham S. , Chaloupka Milani , Hall Martin , Mangel Jeff , Alfaro‐Shigueto Joanna , Dalzell Paul , Ishizaki Asuka 
Published: October 2009

AbstractThere is growing evidence that small‐scale, coastal, passive net fisheries may be the largest single threat to some sea turtle populations. We review assessments of turtle interactions in these fisheries, and experiments on gear‐technology approaches (modifying gear designs, materials and fishing methods) to mitigate turtle by‐catch, available from a small number of studies and fisheries. Additional assessments are needed to improve the limited understanding of the relative degree of risk coastal net fisheries pose to turtle populations, to prioritize limited conservation resources and identify suitable mitigation opportunities. Whether gear technology provides effective and commercially viable solutions, alone or in combination with other approaches, is not well‐understood. Fishery‐specific assessments and trials are needed, as differences between fisheries, including in gear designs; turtle and target species, sizes and abundance; socioeconomic context; and practicality affect efficacy and suitability of by‐catch mitigation methods. Promising gear‐technology approaches for gillnets and trammel nets include: increasing gear visibility to turtles but not target species, through illumination and line materials; reducing net vertical height; increasing tiedown length or eliminating tiedowns; incorporating shark‐shaped silhouettes; and modifying float characteristics, the number of floats or eliminating floats. Promising gear‐technology approaches for pound nets and other trap gear include: replacing mesh with ropes in the upper portion of leaders; incorporating a turtle releasing device into traps; modifying the shape of the trap roof to direct turtles towards the location of an escapement device; using an open trap; and incorporating a device to prevent sea turtle entrance into traps.
WOMEN AND GIRLS AS UPPER PALAEOLITHIC CAVE ‘ARTISTS’: DECIPHERING THE SEXES OF FINGER FLUTERS IN ROUFFIGNAC CAVE
Authors: VAN GELDER LESLIE , SHARPE KEVIN 
Published: October 2009

SummaryPopular and scholarly literature usually assumes that prehistoric artists were adult men. We show in other publications that young children from the Palaeolithic fluted in Rouffignac Cave, France, and hence the incorrectness at least here of the usual assumption. Our research also shows that females as well as males fluted in Rouffignac. Our methods for demonstrating this are forensic based on physiological research of relative finger lengths of males and females. We examine the profiles of the flutings of seven individuals and show that two are probably male whereas the remaining five are probably female. This type of study leading to where we identify individuals can produce responses to social questions about the fluters both as a group and as individuals.
VISUAL AFFORDANCE, LANDSCAPE, AND THE MEGALITHS OF ALDERNEY
Authors: GILLINGS MARK 
Published: October 2009

SummaryThe core of this paper seeks to make a methodological contribution to the GIS‐based analysis of visibility as a potential locational factor in past landscape placement, an area of study whose utility and value have been hotly debated by archaeologists keen to promote more experiential approaches to the interpretation of past landscapes. In doing so it seeks to break with recent discussions on the topic by not show‐casing new or technically more sophisticated sets of approaches. Instead it backtracks to reclaim a methodology introduced over a decade ago, yet rarely applied in routine archaeological practice – a case of taking one step back to advance two steps forward. An important subtext is that for the utility of GIS‐based work to be appreciated, it has to be driven by a clear archaeological research programme. To this end the study is fully embedded in a current research initiative exploring the megalithic monuments of prehistoric Alderney, the northernmost of the Channel Islands.
SIMULATING THE WESTERN SEAWAYS
Authors: CALLAGHAN RICHARD , SCARRE CHRIS 
Published: October 2009

SummaryRecent debates on the introduction of Neolithic features to Britain have emphasized the role of the western maritime routes and the possibility of direct or indirect connections from Brittany to Ireland and Argyll. Here we present the results of simulation modelling of maritime voyaging by paddled or sail‐powered boat, indicating the likely lengths of the journeys that would have been required. The issue of direct travel vs. short crossings and coasting is explored, and the implications for specific connections, such as those posited to account for cattle remains in a pre‐Neolithic context in Ireland, are considered.
LEGACIES OF CHANGE: THE SHAPING OF CULTURAL LANDSCAPES IN A MARGINAL MEDITERRANEAN MOUNTAIN RANGE, THE GARRAF MASSIF, NORTH‐EASTERN SPAIN
Authors: EJARQUE ANA , ORENGO HECTOR A. 
Published: October 2009

SummaryHuman conceptions of landscape have influenced the shaping of landscapes as much as landscape configurations have modelled human perceptions. In this article a new theoretical approach to long‐term cumulative landscape change is tested on the Garraf Massif (Baix Llobregat, north‐eastern Spain). Thanks to its ancient occupation, physical character and location near to the city of Barcelona, the area provides a good illustration of how human‐induced landscape change has shaped new, and sometimes conflicting, landscape perceptions. These perceptions then play an equally active role in altering the previously ‘inherited landscape’ in a long‐term cyclical process that can be studied through the combined use of historical, palaeoenvironmental and archaeological records.
Inactivation of neuronal forebrain A2A receptors protects dopaminergic neurons in a mouse model of Parkinson’s disease
Authors: Carta Anna R. , Kachroo Anil , Schintu Nicoletta , Xu Kui , Schwarzschild Michael A. , Wardas Jadwiga , Morelli Micaela 
Published: October 2009

AbstractAdenosine A2A receptors antagonists produce neuroprotective effects in animal models of Parkinson’s disease (PD). As neuroinflammation is involved in PD pathogenesis, both neuronal and glial A2A receptors might participate to neuroprotection. We employed complementary pharmacologic and genetic approaches to A2A receptor inactivation, in a multiple MPTP mouse model of PD, to investigate the cellular basis of neuroprotection by A2A antagonism. MPTP·HCl (20 mg/kg daily for 4 days) was administered in mice treated with the A2A antagonist SCH58261, or in conditional knockout mice lacking A2A receptors on forebrain neurons (fbnA2AKO mice). MPTP‐induced partial loss of dopamine neurons in substantia nigra pars compacta (SNc) and striatum (Str), associated with increased astroglial and microglial immunoreactivity in these areas. Astroglia was similarly activated 1, 3, and 7 days after MPTP administration, whereas maximal microglial reactivity was detected on day 1, returning to baseline 7 days after MPTP administration. SCH58261 attenuated dopamine cell loss and gliosis in SNc and Str. Selective depletion of A2A receptors in fbnA2AKO mice completely prevented MPTP‐induced dopamine neuron degeneration and gliosis in SNc, and partially counteracted gliosis in Str. Results provide evidence of a primary role played by neuronal A2A receptors in neuroprotective effects of A2A antagonists in a multiple MPTP injections model of PD. With the symptomatic antiparkinsonian potential of several A2A receptor antagonists being pursued in clinical trials, this study adds to the rationale for broader clinical benefit and use of these drugs early in the treatment of PD.
Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged human skin
Authors: Rittié Laure , Stoll Stefan W. , Kang Sewon , Voorhees John J. , Fisher Gary J. 
Published: October 2009

SummarySkin hair follicles (HF) contain bulge stem cells (SC) that regenerate HFs during hair cycles, and repair skin epithelia following injury. As natural aging is associated with decreased skin repair capacity in humans, we have investigated the impact of age on human scalp HF bulge cell number and function. Here, we isolated human bulge cells, characterized as CD200+/KRT15+/KRT19+ cells of the HF, by dissection‐combined CD200 selection in young and aged human skin. Targeted transcriptional profiling indicates that KRT15, KRT19, Dkk3, Dkk4, Tcf3, S100A4, Gas1, EGFR and CTGF/CCN2 are also preferentially expressed by human bulge cells, compared to differentiated HF keratinocytes (KC). Our results demonstrate that aging does not alter expression or localization of these HF SC markers. In addition, we could not detect significant differences in HF density or bulge cell number between young and aged human scalp skin. Interestingly, hedgehog (Hh) signaling is activated in human bulge cells in vivo, and down‐regulated in differentiated HF KCs, both in young and aged skin. In addition, activation of Hh signaling by lentivirus‐mediated overexpression of transcription factor Gli1 induces transcription of HF SC markers KRT15, KRT19, and Gas1, in cultured KCs. Together with previously reported knock‐out mouse results, these data suggest a role for Hh signaling in maintaining bulge cell phenotype in young and aged human skin.
Visualization of gene expression in the live subject using the Na/I symporter as a reporter gene: applications in biotherapy
Authors: Baril Patrick , Martin‐Duque Pilar , Vassaux Georges 
Published: October 2009

Biotherapies involve the utilization of antibodies, genetically modified viruses, bacteria or cells for therapeutic purposes. Molecular imaging has the potential to provide unique information that will guarantee their biosafety in humans and provide a rationale for the future development of new generations of reagents. In this context, non‐invasive imaging of gene expression is an attractive prospect, allowing precise, spacio‐temporal measurements of gene expression in longitudinal studies involving gene transfer vectors. With the emergence of cell therapies in regenerative medicine, it is also possible to track cells injected into subjects. In this context, the Na/I symporter (NIS) has been used in preclinical studies. Associated with a relevant radiotracer (123I‐, 124I‐, 99mTcO4‐), NIS can be used to monitor gene transfer and the spread of selectively replicative viruses in tumours as well as in cells with a therapeutic potential. In addition to its imaging potential, NIS can be used as a therapeutic transgene through its ability to concentrate therapeutic doses of radionuclides in target cells. This dual property has applications in cancer treatment and could also be used to eradicate cells with therapeutic potential in the case of adverse events. Through experience acquired in preclinical studies, we can expect that non‐invasive molecular imaging using NIS as a transgene will be pivotal for monitoring in vivo the exact distribution and pharmacodynamics of gene expression in a precise and quantitative way. This review highlights the applications of NIS in biotherapy, with a particular emphasis on image‐guided radiotherapy, monitoring of gene and vector biodistribution and trafficking of stem cells.This article is part of a themed section on Imaging in Pharmacology. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00685.x
Irbesartan‐mediated reduction of renal and cardiac damage in insulin resistant JCR : LA‐cprats
Authors: Russell JC , Kelly SE , Vine DF , Proctor SD 
Published: October 2009

Background and purpose: Angiotensin II receptor antagonists (ARBs), originally developed for antihypertensive properties, have pleiotropic effects including direct vascular actions. We tested the hypothesis that the ARB irbesartan would be effective against micro‐ and macrovascular complications of the prediabetic metabolic syndrome using the obese, insulin‐resistant JCR : LA‐cprat that exhibits micro‐ and macrovascular disease with ischaemic myocardial lesions and renal disease.Experimental approach: Obese male rats were treated with irbesartan (30 mg·kg−1·day−1, incorporated into chow) from 12 to 25 weeks of age.Key results: Irbesartan treatment caused no change in food intake or body weight. Fasting glycaemic control of the JCR : LA‐cprats was marginally improved, at the expense of increased plasma insulin levels (∼50%). Fasting plasma triglycerides were marginally reduced (∼25%), while cholesterol concentrations were unchanged. Elevated concentrations of adiponectin, monocyte chemotactic protein‐1 and plasminogen activator inhibitor‐1 were reduced along with severity of glomerular sclerosis. Macrovascular dysfunction (aortic hypercontractile response to noradrenergic stimulus and reduced endothelium‐dependent relaxation) was improved and frequency of ischaemic myocardial lesions reduced (62%).Conclusions and implications: Irbesartan reduces markers of inflammation and prothombotic status, improves macrovascular function and reduces glomerular sclerosis and myocardial lesions in a model of the metabolic syndrome. Unlike pharmaceutical agents targeted on metabolic dysfunction, irbesartan reduced end‐stage disease without major reduction of plasma lipids or insulin. The protective effects appear to be secondary to unknown intracellular mechanisms, probably involving signal transduction pathways. Understanding these would offer novel pharmaceutical approaches to protection against cardiovascular disease.
Differential effects of quercetin, apigenin and genistein on signalling pathways of protease‐activated receptors PAR1and PAR4in platelets
Authors: Navarro‐Núñez L , Rivera J , Guerrero JA , Martínez C , Vicente V , Lozano ML 
Published: October 2009

Background and purpose: The modulation by flavonoids of platelet responses induced by thrombin has been little investigated, and the antiplatelet activity, as well as possible inhibitory mechanisms of these compounds on thrombin signalling, has not yet been elucidated. We explored whether flavonoids affect platelet signalling pathways triggered by thrombin and by the selective activation of its protease‐activated receptors (PARs) 1 and 4, and analysed the antagonism of these polyphenols at thrombin receptors.Experimental approach: We investigated the effect of a range of polyphenolic compounds on platelet aggregation, 5‐HT secretion, intracellular calcium mobilization, protein kinase activity and tyrosine phosphorylation, triggered by thrombin and PAR agonist peptides (PAR‐APs). The ability of these flavonoids to bind to thrombin receptors was investigated by competitive radioligand binding assays using125I‐thrombin.Key results: Quercetin, apigenin and genistein impaired platelet aggregation, as well as 5‐HT release and calcium mobilization, induced by thrombin and PAR‐APs. Quercetin and apigenin were inhibitors of protein kinases, but genistein exhibited a minimal ability to suppress platelet phosphorylation. Binding assays did not establish any kind of interaction between thrombin receptors and any of the flavonoids tested.Conclusions and implications: Quercetin, apigenin and genistein did not inhibit thrombin responses by interacting with thrombin receptors, but by interfering with intracellular signalling. While inhibition by genistein may be a consequence of affecting calcium mobilization, subsequent platelet secretion and aggregation, for quercetin and apigenin, inhibition of kinase activation may also be involved in the impairment of platelet responses.