bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential transport of platinum compounds by the human organic cation transporter hOCT2 (hSLC22A2)
Authors: Burger H , Zoumaro‐Djayoon A , Boersma AWM , Helleman J , Berns EMJJ , Mathijssen RHJ , Loos WJ , Wiemer EAC 
Published: January 2010

Background:  Solute carriers (SLCs), in particular organic cation transporters (OCTs), have been implicated in the cellular uptake of platinum‐containing anticancer compounds. The activity of these carriers may determine the pharmacokinetics and the severity of side effects, including neuro‐ and nephrotoxicity of platinum‐based chemotherapy. As decreased drug accumulation is a key mechanism of platinum resistance, SLCs may also contribute to the development of resistance. Here, we define the role of hSLC22A2 (OCT2) in the cellular uptake of platinum compounds.Experimental approach:  Human embryonic kidney (HEK) 293 cells stably expressing the hSLC22A2 gene (HEK293/hSLC22A2) were used in platinum accumulation studies. Following a 2 h exposure to various platinum compounds (100 µM), intracellular platinum levels were determined by flameless atomic absorption spectrometry.Key results:  HEK293/hSLC22A2 cells, compared with HEK293/Neo control cells, displayed significant increases in oxaliplatin (28.6‐fold), Pt[DACH]Cl2 (20.6‐fold), ormaplatin (8.1‐fold), tetraplatin (4.5‐fold), transplatin (3.7‐fold) and cisplatin (1.3‐fold), but not carboplatin. SLC22A2‐mediated transport could be inhibited by 1‐methyl‐4‐phenylpyridinium. Furthermore, hSLC22A2‐mediated oxaliplatin and cisplatin accumulation was time‐ and concentration‐dependent, but non‐saturable. Expression of hSLC22A2 in HEK293 cells resulted in enhanced sensitivity to oxaliplatin (12‐fold) and cisplatin (1.8‐fold). Although, hSLC22A2 mRNA expression was frequently found in ovarian cancer cell lines, its expression in clinical ovarian cancer specimens (n= 80) was low and did not correlate with the treatment outcome of platinum‐based regimens.Conclusions and implications:  The hSLC22A2 drug transporter is a critical determinant in the uptake and cytotoxicity of various platinum compounds, particularly oxaliplatin.
In vitro and in vivo antineoplastic activity of a novel bromopyrrole and its potential mechanism of action
Authors: Xiong Sheng , Pang Hui‐dan , Fan Jun , Ge Feng , Yang Xiao‐xia , Liu Qiu‐ying , Liao Xiao‐jian , Xu Shi‐hai 
Published: January 2010

Background and purpose:  Many bromopyrrole compounds have been reported to have in vitro antineoplastic activity. In a previous study, we isolated N‐(4, 5‐dibromo‐pyrrole‐2‐carbonyl)‐L‐amino isovaleric acid methyl ester (B6) from marine sponges. Here, we investigated the in vitro and in vivo antineoplastic activity of B6 and its potential mechanism.Experimental approach:  The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay was used to determine the in vitro antineoplastic activity of B6. Flow cytometry, western blot analysis and morphological observations were used to investigate its mechanism of action. A mouse xenograft model was used to determine its in vivo activity.Key results:  B6 inhibited the proliferation of various human cancer cells in vitro, with highest activity on LOVO and HeLa cells. B6 also exhibited significant growth inhibitory effects in vivo in a xenograft mouse model. Acute toxicity analysis suggested that B6 has low toxicity. B6‐treated cells arrested in the G1 phase of the cell cycle and had an increased fraction of sub‐G1 cells. In addition, the population of Annexin V‐positive/propidium iodide‐negative cells increased, indicating the induction of early apoptosis. Indeed, B6‐treated cells exhibited morphologies typical of cells undergoing apoptosis. Western blotting showed cleaved forms of caspase‐9 and caspase‐3 in cells exposed to B6. Moreover, B6‐promoted Ca2+ release and apoptosis was associated with elevated intracellular Ca2+concentration.Conclusions and implications:  B6 has significant antineoplastic activity in vitro as well as in vivo. It inhibits tumour cell proliferation by arresting the cell cycle and inducing apoptosis. With its low toxicity, B6 represents a promising antineoplastic, primary compound.
Staphylococcus aureus Bloodstream Infections in Older Adults: Clinical Outcomes and Risk Factors for In‐Hospital Mortality
Authors: Big Cecilia , Malani Preeti N. 
Published: January 2010

OBJECTIVES: To assess clinical outcomes and identify risk factors for mortality in older adults with Staphylococcus aureus bloodstream infection (SAB).DESIGN: Retrospective review.SETTING: University of Michigan Health System, Ann Arbor.PARTICIPANTS: All patients aged 80 and older with SAB between January 2004 and July 2008.MEASUREMENTS: Clinical data, including comorbid conditions, SAB source, echocardiography results, Charlson Comorbidity Index, mortality (in‐hospital and 6‐month), and need for rehospitalization or chronic care after discharge.RESULTS: Seventy‐six patients aged 80 and older (mean 85.5 ± 4.2) with SAB were identified. Infection sources included 14 (18.4%) vascular catheter associated, 16 (21.1%) wound related, seven (9.2%) endocarditis, five (6.6%) intravascular, and 19 (25%) with unknown source; 46 (60.5%) patients had methicillin‐resistant strains. Twenty‐two (28.9%) patients underwent surgery or device placement within 30 days of developing SAB; 10 of these 22 had SAB associated with surgical site infection (SSI). Twenty two (28.9%) patients died in the hospital or were discharged to hospice care; at least 43 (56.6%) patients died within 6 months of presentation, and eight were lost to follow‐up. Unknown source of bacteremia (odds ratio=5.2, P=.008) was independently associated with in‐hospital death. Echocardiography was not pursued in 45% of patients. Of surviving patients, 40 (74.1%) required skilled care after discharge; eight (20%) required rehospitalization.CONCLUSION: SAB was associated with high mortality rates in patients aged 80 and older. The observed association between SAB and SSI may direct preventive strategies such as perioperative decolonization or antimicrobial prophylaxis. Interventions to optimize clinical care practices in elderly patients with SAB are essential given the associated morbidity and mortality.
Determinants of Early Reductions in Drinking in Older At‐Risk Drinkers Participating in the Intervention Arm of a Trial to Reduce At‐Risk Drinking in Primary Care
Authors: Lin James C. , Karno Mitchell P. , Barry Kristen L. , Blow Frederic C. , Davis James W. , Tang Lingqi , Moore Alison A. 
Published: January 2010

OBJECTIVES: To describe differences between older at‐risk drinkers, as determined using the Comorbidity Alcohol Risk Evaluation Tool, who reduced drinking and those who did not after an initial intervention and to determine factors associated with early reductions in drinking.DESIGN: Secondary analyses of data from a randomized controlled trial.SETTING: Seven primary care sites.PARTICIPANTS: Subjects randomized to the intervention group who completed the first health educator call approximately 2 weeks after enrollment (n=239).INTERVENTION: Personalized risk reports, booklets on alcohol‐associated risks, and advice from physicians, followed by a health educator call.MEASURMENTS: Reductions in number of alcoholic drinks.RESULTS: Thirty‐nine percent of the sample had reduced drinking within 2 weeks of receiving the initial intervention. According to the final multiple logistic regression model, those who were concerned about alcohol‐related risks (odds ratio (OR)=2.03, 95% confidence interval (CI)=1.01–4.07), read through the educational booklet (OR=2.97, 95% CI=1.48–5.95), or perceived that their physicians discussed risks and advised changing drinking behaviors (OR=4.1, 95% CI=2.02–8.32) had greater odds of reducing drinking by the first health educator call.CONCLUSION: Concern about risks, reading educational material, and perception of physicians providing advice to reduce drinking were associated with early reductions in alcohol use in older at‐risk drinkers. Understanding these factors will enable development of better intervention strategies to reduce unhealthy alcohol use.
Hyperpolarized Views on the Roles of the Hyperpolarization-Activated Channels in Neuronal Excitability
Authors: Noam Yoav , Baram Tallie Z. 
Published: January 2010

Upregulated H-Current in Hyperexcitable CA1 Dendrites after Febrile Seizures. Dyhrfjeld-Johnsen J, Morgan RJ, Csaba Foldy, Soltesz I., Front Cell Neurosci. 2008;2:2. doi:10.3389/neuro.03.002.2008. Somatic recordings from CA1 pyramidal cells indicated a persistent upregulation of the h-current ( Ih) after experimental febrile seizures. Here, we examined febrile seizure-induced long-term changes in Ih and neuronal excitability in CA1 dendrites. Cell-attached recordings showed that dendritic Ih was significantly upregulated, with a depolarized half-activation potential and increased maximal current. Although enhanced Ih is typically thought to be associated with decreased dendritic excitability, whole-cell dendritic recordings revealed a robust increase in action potential firing after febrile seizures. We turned to computational simulations to understand how the experimentally observed changes in Ih influence dendritic excitability. Unexpectedly, the simulations, performed in three previously published CA1 pyramidal cell models, showed that the experimentally observed increases in Ih resulted in a general enhancement of dendritic excitability, primarily due to the increased Ih-induced depolarization of the resting membrane potential overcoming the excitability-depressing effects of decreased dendritic input resistance. Taken together, these experimental and modeling results reveal that, contrary to the exclusively anti-convulsive role often attributed to increased Ih in epilepsy, the enhanced Ih can co-exist with, and possibly even contribute to, persistent dendritic hyperexcitability following febrile seizures in the developing hippocampus. HCN Hyperpolarization-Activated Cation Channels Inhibit EPSPs by Interactions with M-type K+ Channels. George MS, Abbott LF, Siegelbaum SA. Nat Neurosci 2009;12(5):577–584. The processing of synaptic potentials by neuronal dendrites depends on both their passive cable properties and active voltage-gated channels, which can generate complex effects as a result of their nonlinear properties. We characterized the actions of HCN (hyperpolarization-activated cyclic nucleotide-gated cation) channels on dendritic processing of subthreshold excitatory postsynaptic potentials (EPSPs) in mouse CA1 hippocampal neurons. The HCN channels generated an excitatory inward current ( Ih) that exerted a direct depolarizing effect on the peak voltage of weak EPSPs, but produced a paradoxical hyperpolarizing effect on the peak voltage of stronger, but still subthreshold, EPSPs. Using a combined modeling and experimental approach, we found that the inhibitory action of Ih was caused by its interaction with the delayed-rectifier M-type K+ current. In this manner, Ih can enhance spike firing in response to an EPSP when spike threshold is low and can inhibit firing when spike threshold is high.
Vegetation transition following drainage in a high‐latitude hyper‐oceanic ecosystem
Authors: Fosaa Anna Maria , Olsen Erla , Simonsen William , Gaard Magnus , Hansen Heidi 
Published: January 2010

AbstractQuestions: How does draining affect the composition of vegetation? Are certain functional groups favoured? Can soil parameters explain these differences?Location: Central Faroe Islands, treeless islands in the northern boreal vegetation zone. Since 1987, an area of 21 km2 at 100–200 m a.s.l. was drained in order to provide water for hydro‐electric production.Method: Vegetation and soil of a drained area and a control, undrained neighbouring area of approximately the same size were sampled in 2007. Six sites were sampled in each area. The vegetation was classified with cluster analysis.Results: Four plant communities were defined in the area: Calluna vulgaris–Empetrum nigrum–Vaccinium myrtillus heath, Scirpus cespitosus–Eriophorum angustifolium blanket mire, Carex bigelowii–Racomitrium lanuginosum moss‐heath, Narthecium ossifragum–Carex panacea mire. Heath was more extensively distributed within, and was the dominant community of the drained area, whereas moss‐heath was more extensive in the undrained area. Blanket mire and mire had approximately the same distribution in both areas. For the blanket mire, species composition indicated drier conditions in the drained than in the undrained area. The drained area had higher frequencies of woody species and lichens, grasses had finer roots and available soil phosphate was considerably higher, whereas the undrained area had higher frequencies of grasses and sedges.Conclusion: The dominant plant communities were different in the two areas, which indicated that the blanket mire was drying in the drained area. Higher concentration of soil phosphate in the drained area also indicated increased decomposition of organic soils owing to desiccation.
Floristic diversity in fragmented Afromontane rainforests: Altitudinal variation and conservation importance
Authors: Schmitt Christine B. , Denich Manfred , Demissew Sebsebe , Friis Ib , Boehmer Hans Juergen 
Published: January 2010

AbstractQuestion: How does the floristic diversity of Afromontane rainforests change along an altitudinal gradient? What are the implications for conservation planning in these strongly fragmented forest areas that form part of the Eastern Afromontane Biodiversity Hotspot?Location: Bonga, southwestern Ethiopia.Methods: Based on evidence from other montane forests, we hypothesized that altitude has an effect on the floristic diversity of Afromontane rainforests in southwestern Ethiopia. To test this hypothesis, detailed vegetation surveys were carried out in 62 study plots located in four relatively undisturbed forest fragments situated at altitudes between 1600 m and 2300 m. Floristic diversity was evaluated using a combination of multivariate statistical analyses and diversity indices.Results: Ordination and indicator species analyses showed gradual variations in floristic diversity along the altitudinal gradient with a pronounced shift in species composition at ca. 1830 m. Upper montane forest (>1830 m) is characterized by high fern diversity and indicator species that are Afromontane endemics. Lower montane forest (<1830 m) exhibits a greater diversity of tree species and a higher abundance of the flagship species Coffea arabica.Conclusions: Our results provide crucial ecological background information concerning the montane rainforests of Ethiopia, which have been poorly studied until now. We conclude that both forest types identified during this study need to be considered for conservation because of their particular species compositions. Owing to the high degree of forest fragmentation, conservation concepts should consider a multi‐site approach with at least two protected areas at different altitudinal levels.
The number of taste buds is related to bitter taste sensitivity in layer and broiler chickens
Authors: KUDO Ken‐ichi , SHIRAISHI Jun‐ichi , NISHIMURA Shotaro , BUNGO Takashi , TABATA Shoji 
Published: January 2010

ABSTRACTThe relationship between taste sensitivity and the number of taste buds using a bitter tastant, quinine hydrochloride, was investigated in White Leghorn, Rhode Island Red, and broiler chickens. The White Leghorn and Rhode Island Red strains were able to perceive 2.0 mmol/L quinine hydrochloride, but the taste sensitivity of Rhode Island Red chickens was higher than that of White Leghorn chickens. Broiler chickens perceived 0.5 mmol/L quinine hydrochloride. The number of taste buds in the White Leghorn strain was the lowest, then the Rhode Island Red strain, with the number of taste buds highest in the broiler chickens. The number of taste buds was well correlated with bitter taste sensitivity. Therefore, we suggest that the number of taste buds is a vital factor in the perception of bitter taste and may be useful in selecting appropriate feeds for chickens.
XMM-Newton and INTEGRAL study of the SFXT IGR J18483-0311 in quiescence: hint of a cyclotron emission feature?
Authors: Sguera V. , Ducci L. , Sidoli L. , Bazzano A. , Bassani L. 
Published: January 2010

Abstract
We report the results from archival XMM–Newton and INTEGRAL observations of the Supergiant Fast X-ray Transient (SFXT) IGR J18483−0311 in quiescence. The 18–60 keV hard X-ray behaviour of the source is presented here for the first time; it is characterized by a spectral shape (Γ∼ 2.5) similar to that during outburst activity, and the lowest measured luminosity level is ∼1034 erg s−1. The 0.5–10 keV luminosity state, measured by XMM–Newton during the apastron passage, is about one order of magnitude lower and it is reasonably fitted by an absorbed blackbody model yielding parameters consistent with previous measurements. In addition, we find evidence (∼3.5σ significance) of an emission-like feature at ∼3.3 keV in the quiescent 0.5–10 keV source spectrum. The absence of any known or found systematic effects, which could artificially introduce the observed feature, gives us confidence about its non-instrumental nature. We show that its physical explanation in terms of atomic emission line appears unlikely, and conversely we attempt to ascribe it to an electron cyclotron emission line which would imply a neutron star magnetic field of the order of ∼3 × 1011 G. Importantly, such direct estimation is in very good agreement with that independently inferred by us in the framework of accretion from a spherically symmetric stellar wind. If firmly confirmed by future longer X-ray observations, this would be the first detection ever of a cyclotron feature in the X-ray spectrum of an SFXT, with important implications on theoretical models.
Incidence of Atrial Fibrillation after Percutaneous Closure of Patent Foramen Ovale and Small Atrial Septal Defects in Patients Presenting with Cryptogenic Stroke
Authors: Bonvini R. F. , Sztajzel R. , Dorsaz P.-A. , Righini M. , Bonvin C. , Alibegovic J. , Sigwart U. , Camenzind E. , Verin V. , Sztajzel J. 
Published: January 2010

Objective The occurrence of atrial fibrillation after percutaneous closure of a patent foramen ovale for cryptogenic stroke has been reported in a variable percentage of patients. However, its precise incidence and mechanism are presently unclear and remain to be elucidated. Design Prospective follow-up study. Patients Ninety-two patients undergoing a percutaneous patent foramen ovale closure procedure (closure group) for cryptogenic stroke were compared with a similar group of 51 patients, who were medically treated. Methods A systematic arrhythmia follow-up protocol to assess the incidence of AF was performed including a 7-day event-loop recording at day 1, after 6 and 12 months in patients of the closure group and compared with those of the medically treated group. Results The incidence of AF was similar in both study groups during a follow-up of 12 months, including 7·6% (95% CI: 3·1–15·0%) in the closure and 7·8% (95% CI: 2·18–18·9%) in the medically treated group ( P = 1·0). The presence of a large patent foramen ovale was the only significant risk factor for the occurrence of AF as demonstrated by a multivariate Cox regression analysis (95% CI, 1·275–20·018; P = 0·021). Conclusions Our findings indicate that patients with cryptogenic stroke and patent foramen ovale have a rather high incidence of AF during a follow-up of 12 months. Atrial fibrillation occurred with a similar frequency whether the patent foramen ovale/atrial septal defect was successfully percutaneously closed or was medically managed. The presence of a large patent foramen ovale was the only significant predictor of AF occurrence during follow-up.
Effectiveness of Virtual Reality Exercises in STroke Rehabilitation (EVREST): Rationale, Design, and Protocol of a Pilot Randomized Clinical Trial Assessing the Wii Gaming System
Authors: Saposnik G. , Mamdani M. , Bayley M. , Thorpe K.E. , Hall J. , Cohen L.G. , Teasell R. 
Published: January 2010

Background Evidence suggests that increasing intensity of rehabilitation results in better motor recovery. Limited evidence is available on the effectiveness of an interactive virtual reality gaming system for stroke rehabilitation. EVREST was designed to evaluate feasibility, safety and efficacy of using the Nintendo Wii gaming virtual reality (VRWii) technology to improve arm recovery in stroke patients. Methods Pilot randomized study comparing, VRWii versus recreational therapy (RT) in patients receiving standard rehabilitation within six months of stroke with a motor deficit of ≥3 on the Chedoke-McMaster Scale (arm). In this study we expect to randomize 20 patients. All participants (age 18–85) will receive customary rehabilitative treatment consistent of a standardized protocol (eight sessions, 60 min each, over a two-week period). Outcome measures The primary feasibility outcome is the total time receiving the intervention. The primary safety outcome is the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, will be measured by the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at the four-week follow-up visit. From November, 2008 to September, 2009 21 patients were randomized to VRWii or RT. Mean age, 61 (range 41–83) years. Mean time from stroke onset 25 (range 10–56) days. Conclusions EVREST is the first randomized parallel controlled trial assessing the feasibility, safety, and efficacy of virtual reality using Wii gaming technology in stroke rehabilitation. The results of this study will serve as the basis for a larger multicentre trial. ClinicalTrials.gov registration# NTC692523
GnRH blockers: a changing paradigm in the management of prostate cancer
Authors: Drudge‐Coates Lawrence 
Published: January 2010

For more than 60 years, androgen deprivation therapy, first with orchidectomy and more recently with gonadotrophin‐releasing hormone (GnRH) agonists, has been a key treatment approach in the management of advanced prostate cancer. In spite of showing comparable survival benefits, these two treatments are associated with both physical and psychological issues, with notable effects on patient quality of life.The development of GnRH blockers provides a new class of hormonal agent with a different, direct mode of action. Degarelix, a newly approved GnRH blocker, has displayed a fast, profound and sustained suppression of testosterone and prostate‐specific antigen levels without subsequent tumour flare effects. This paper considers the current evidence for this new treatment approach and how this may impact on current urology nursing practice.
Cryoablation for prostate cancer: an overview about background, procedure and nurses' responsibilities
Authors: Hieronymi Susanne , Witzsch Ulrich 
Published: January 2010

Cryoablation was introduced in clinical practice for the treatment of skin lesions more than 100 years ago. Treatment to other areas of the body followed including the liver, lungs, bones, corneas and nerves, with applications extended to use in analgesia. The potential of using cryoablation for treatment of the prostate has been recognized as a therapeutic option for more than half a century. However, early results were unsatisfactory due to poor oncological outcome and the high morbidity of the procedure. Cryotherapy has evolved dramatically during the last decades with an improvement in technique, resulting in a significant reduction of complication rates and improved outcome for patients.Although it is regarded as a minimally invasive therapy, there are several nursing aspects that have to be observed pre‐ intra‐ and postoperatively which are essential to ensure that the patient's recovery is effected and that all benefits of a minimally invasive therapy are achieved.