bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retracted: CXCL12/CXCR4 chemokine signaling in spinal glia induces pain hypersensitivity through MAPKs‐mediated neuroinflammation in bone cancer rats
Authors: Hu Xue‐Ming , Liu Yan‐Nan , Zhang Hai‐Long , Cao Shou‐Bin , Zhang Ting , Chen Li‐Ping , Shen Wen 
Published: November 2014

AbstractThe activation of MAPK pathways in spinal cord and subsequent production of proinflammatory cytokines in glial cells contribute to the development of spinal central sensitization, the basic mechanism underlying bone cancer pain (BCP). Our previous study showed that spinal CXCL12 from astrocytes mediates BCP generation by binding to CXCR4 in both astrocyters and microglia. Here, we verified that CXCL12/CXCR4 signaling contributed to BCP through a MAPK‐mediated mechanism. In naïve rats, a single intrathecal administration of CXCL12 considerably induced pain hyperalgesia and phosphorylation expression of spinal MAPK members (including extracellular signal‐regulated kinase, p38, and c‐Jun N‐terminal kinase), which could be partially prevented by pre‐treatment with CXCR4 inhibitor AMD3100. This CXCL12‐induced hyperalgesia was also reduced by MAPK inhibitors. In bone cancer rats, tumor cell inoculation into the tibial cavity caused prominent and persistent pain hyperalgesia, and associated with up‐regulation of CXCL12 and CXCR4, activation of glial cells, phosphorylation of MAPKs, and production of proinflammatory cytokines in the spinal cord. These tumor cell inoculation‐induced behavioral and neurochemical alterations were all suppressed by blocking CXCL12/CXCR4 signaling or MAPK pathways. Taken together, these results demonstrate that spinal MAPK pathways mediated CXCL12/CXCR4‐induced pain hypersensitivity in bone cancer rats, which could be druggable targets for alleviating BCP and glia‐derived neuroinflammation.
imageFollowing tumor cell inoculation, chemokine CXCL12 from astrocytes spreads around the spinal environment, resulting in functional activation of CXCR4‐expressing astrocytes and microglia. Once glia are activated, they may initiate MAPK (mitogen‐activated protein kinase) pathways, and subsequently produce proinflammatory cytokines and chemokines. Among them, CXCL12 could reinforce the astrocytic and microglial activation in autocrine and paracrine manners. Such positive feedback loops sustain perseverant neuroinflammation, facilitate glial activation, and finally lead to bone cancer pain. IL = interleukin; TNF = tumor necrosis factor.
S‐allyl cysteine activates the Nrf2‐dependent antioxidant response and protects neurons against ischemic injury in vitro and in vivo
Authors: Shi Huanying , Jing Xu , Wei Xinbing , Perez Ruth G. , Ren Manru , Zhang Xiumei , Lou Haiyan 
Published: November 2014

AbstractStroke is a devastating clinical condition for which an effective neuroprotective treatment is currently unavailable. S‐allyl cysteine (SAC), the most abundant organosulfur compound in aged garlic extract, has been reported to possess neuroprotective effects against stroke. However, the mechanisms underlying its beneficial effects remain poorly defined. The present study tests the hypothesis that SAC attenuates ischemic neuronal injury by activating the nuclear factor erythroid‐2‐related factor 2 (Nrf2)‐dependent antioxidant response in both in vitro and in vivo models. Our findings demonstrate that SAC treatment resulted in an increase in Nrf2 protein levels and subsequent activation of antioxidant response element pathway genes in primary cultured neurons and mice. Exposure of primary neurons to SAC provided protection against oxygen and glucose deprivation‐induced oxidative insults. In wild‐type (Nrf2+/+) mice, systemic administration of SAC attenuated middle cerebral artery occlusion‐induced ischemic damage, a protective effect not observed in Nrf2 knockout (Nrf2−/−) mice. Taken together, these findings provide the first evidence that activation of the Nrf2 antioxidant response by SAC is strongly associated with its neuroprotective effects against experimental stroke and suggest that targeting the Nrf2 pathway may provide therapeutic benefit for the treatment of stroke.
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The transcription factor Nrf2 is involved in cerebral ischemic disease and may be a promising target for the treatment of stroke. We provide novel evidence that SAC confers neuroprotection against ischemic stroke by activating the antioxidant Nrf2 signaling pathway. ARE, antioxidant response element; GCLC, glutathione cysteine ligase regulatory subunit; GCLM, glutathione cysteine ligase modulatory subunit; HO‐1, heme oxygenase‐1; JNK, c‐Jun N‐terminal kinase; Keap1, Kelch‐like ECH‐associated protein 1; Maf, musculoaponeurotic fibrosarcoma; Nrf2, nuclear factor erythroid‐2‐related factor 2; SAC, S‐allyl cysteine; ROS, reactive oxygen species.
Pre‐synaptic C‐terminal truncated tau is released from cortical synapses in Alzheimer's disease
Authors: Sokolow Sophie , Henkins Kristen M. , Bilousova Tina , Gonzalez Bianca , Vinters Harry V. , Miller Carol A. , Cornwell Lindsey , Poon Wayne W. , Gylys Karen H. 
Published: November 2014

AbstractThe microtubule‐associated protein tau has primarily been associated with axonal location and function; however, recent work shows tau release from neurons and suggests an important role for tau in synaptic plasticity. In our study, we measured synaptic levels of total tau using synaptosomes prepared from cryopreserved human postmortem Alzheimer's disease (AD) and control samples. Flow cytometry data show that a majority of synaptic terminals are highly immunolabeled with the total tau antibody (HT7) in both AD and control samples. Immunoblots of synaptosomal fractions reveal increases in a 20 kDa tau fragment and in tau dimers in AD synapses, and terminal‐specific antibodies show that in many synaptosome samples tau lacks a C‐terminus. Flow cytometry experiments to quantify the extent of C‐terminal truncation reveal that only 15–25% of synaptosomes are positive for intact C‐terminal tau. Potassium‐induced depolarization demonstrates release of tau and tau fragments from pre‐synaptic terminals, with increased release from AD compared to control samples. This study indicates that tau is normally highly localized to synaptic terminals in cortex where it is well‐positioned to affect synaptic plasticity. Tau cleavage may facilitate tau aggregation as well as tau secretion and propagation of tau pathology from the pre‐synaptic compartment in AD.
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Results demonstrate the abundance of tau, mainly C‐terminal truncated tau, in synaptic terminals in aged control and in Alzheimer's disease (AD) samples. Tau fragments and dimers/oligomers are prominent in AD synapses. Following depolarization, tau release is potentiated in AD nerve terminals compared to aged controls. We hypothesize (i) endosomal release of the different tau peptides from AD synapses, and (ii) together with phosphorylation, fragmentation of synaptic tau exacerbates tau aggregation, synaptic dysfunction, and the spread of tau pathology in AD. Aβ = amyloid‐beta.
Fluctuations in nucleus accumbens extracellular glutamate and glucose during motivated glucose‐drinking behavior: dissecting the neurochemistry of reward
Authors: Wakabayashi Ken T. , Myal Stephanie E. , Kiyatkin Eugene A. 
Published: November 2014

AbstractWhile motivated behavior involves multiple neurochemical systems, few studies have focused on the role of glutamate, the brain's excitatory neurotransmitter, and glucose, the energetic substrate of neural activity in reward‐related neural processes. Here, we used high‐speed amperometry with enzyme‐based substrate‐sensitive and control, enzyme‐free biosensors to examine second‐scale fluctuations in the extracellular levels of these substances in the nucleus accumbens shell during glucose‐drinking behavior in trained rats. Glutamate rose rapidly after the presentation of a glucose‐containing cup and before the initiation of drinking (reward seeking), decreased more slowly to levels below baseline during consumption (sensory reward), and returned to baseline when the ingested glucose reached the brain (metabolic reward). When water was substituted for glucose, glutamate rapidly increased with cup presentation and in contrast to glucose drinking, increased above baseline after rats tasted the water and refused to drink further. Therefore, extracellular glutamate show distinct changes associated with key events of motivated drinking behavior and opposite dynamics during sensory and metabolic components of reward. In contrast to glutamate, glucose increased at each stimulus and behavioral event, showing a sustained elevation during the entire behavior and a robust post‐ingestion rise that correlated with the gradual return of glutamate levels to their baseline. By comparing active drinking with passive intra‐gastric glucose delivery, we revealed that fluctuations in extracellular glucose are highly dynamic, reflecting a balance between rapid delivery because of neural activity, intense metabolism, and the influence of ingested glucose reaching the brain.
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By using enzyme‐based biosensors coupled with high‐speed amperometry, we examined the pattern of dynamic fluctuations in extracellular levels of glutamate and glucose in the nucleus accumbens during glucose‐drinking behavior in trained rats. These fluctuations are considered with respect to their functional significance in motivated behavior and their relation to sensory and metabolic aspects of reward.
Improvement of communication and interpersonal competence in telenursing – development of a self‐assessment tool
Authors: Johnson Christina , Wilhelmsson Susan , Börjeson Sussanne , Lindberg Malou 
Published: November 2014

Aims and objectivesThe aim of this study was to develop a self‐assessment tool aiming to raise telenurses' awareness of their communication and interpersonal competence, and highlight areas in need of improvement.BackgroundSeveral studies have revealed the need for development of communication competence in telenursing. Structured analyses of conversations with patients/callers, is one way to increase telenurses' awareness of their unique communication and interpersonal competence.DesignInstrument development, Validation assessment using the method Content Validity Index.MethodThe process to determine content validity was done in two stages; the development stage and the assessment stage. The development stage started with a literature search. The assessment stage was separated into two phases, assessment by an expert group and assessment and test by telenurses. The telenurses also participated in consensus discussions.ResultsA telenursing self‐assessment tool with 58 items was developed. The items were sorted into five sections according to the nursing process.ConclusionThis study describes the thorough development process of the telenursing self‐assessment tool to be used by telenurses in order to become aware of their unique communication and interpersonal competence when analysing their own conversations with patients/callers. As a formative tool it is meant to provide self‐direction, feedback and coaching, and create learning opportunities.Relevance to clinical practiceThe self‐assessment tool helps the telenurse to follow the nursing process, to be patient‐centred, and it is meant to provide self‐direction, feedback, and coaching, as well as create learning opportunities. The tool can contribute to the development of communication and interpersonal competence in telephone advice nursing. Further development of the tool may provide an objective scoring instrument for evaluating communication training and education in the field.
Patient‐specific risk factors of adverse drug events in adult inpatients – evidence detected using the Global Trigger Tool method
Authors: Härkänen Marja , Kervinen Marjo , Ahonen Jouni , Voutilainen Ari , Turunen Hannele , Vehviläinen‐Julkunen Katri 
Published: November 2014

Aims and objectivesTo identify the prevalence, preventability, and severity of adverse drug events in randomly selected adult hospital inpatients, and to study the association between adverse drug events and patient‐specific factors.BackgroundAdverse drug events represent one of the major concerns in patient safety.DesignA retrospective record review.MethodsThe study was conducted in an 800‐bed university hospital in Finland within a 12‐month period. Retrospective reviews of randomly selected discharged patients' (n = 463) records using the Global Trigger Tool method were undertaken. The prevalence, preventability, and severity of adverse drug events were studied, and the association between patient‐specific factors and adverse drug events were examined using a binary logistic regression model and Pearson's chi‐squared tests.ResultsA total of 180 adverse drug events were detected in 125 (27%) patients, of which 74 (41·1%) were preventable, and 94·4% caused temporary harm. An abnormal level of potassium in the blood was the most frequent adverse drug event (n = 37). The risk of adverse drug events increased with the length of hospital stay and the increased number of drugs patients used. The patients with coronary diseases (n = 130) had a 2·5 times higher risk of experiencing adverse drug events. In addition, the risk of adverse drug events during hospitalisation increased together with the co‐morbidity of patients.ConclusionsAdverse drug events were experienced by a quarter of inpatients, while severe adverse drug events were rare. The risk of adverse drug events increased with patients' prolonged hospital stay, polypharmacy, and morbidity. In addition, information of the usefulness of the Global Trigger tool can be used for future development of the method.Relevance to clinical practicePatient‐specific risk factors were identified using the Global Trigger Tool method revealing that more efficient monitoring of inpatients with these risk factors may be profitable for decreasing adverse drug events.
A pioneer of Australian paediatrics: Dr Henry Edward Brown (1858–1931)
Authors: Isles Alan F , Roper Peter , Pearn John H 
Published: November 2014

AbstractThe emergence of paediatrics as a specialty in Australian medicine dates from the last two decades of the 19th century. Among the pioneers of pre‐Federation paediatrics, we include Dr Henry Edward Brown (1858–1931), an Irish‐born physician and surgeon who became the first paediatrician to practise in the northern half of the Australian continent. In 1885, he was appointed as the medical superintendent of the Rockhampton Children's Hospital, itself a pioneer institution in the care of sick and injured children. Dr H.E. Brown also served as medical officer of health concurrently in three Queensland shires. He was a leader in the literary and sporting life of the busy port town of Rockhampton and a scholar and significant philanthropist in the domain of French literature. His life was and remains an exemplar of a class of pre‐Federation paediatricians who established the ethos of clinical and societal service, which remains as a core feature of the speciality discipline of paediatrics in the 21st century.
Across the great divide: Proximate units at the lexical‐phonological interface
Authors: O'Séaghdha Padraig G. 
Published: November 2014

AbstractEvidence that languages differ in the initial, proximate units of phonological encoding presents a challenge to current theories of language production. The proximate units principle is the idea that variation in the proximate, first selectable, phonological units during word form retrieval for speaking is key to understanding the implementation of phonological encoding in diverse languages. It proposes that rather than imposing a unilingual phonemic template across languages, the variety of proximate units should be incorporated in theories. From this perspective, cross‐linguistic differences in speech error patterns, in phonological preparation, in automatic activation, in multi‐word coordination, and in metalinguistic awareness are more clearly interpretable. The proximate units perspective aims to accelerate scientific progress by incorporating linguistic diversity at the lexical‐phonological interface into theories of word and sentence production.
Do not disturb the family: roles of colony size and human disturbance in the genetic structure of lesser kestrel
Authors: Di Maggio R. , Mengoni C. , Mucci N. , Campobello D. , Randi E. , Sarà M. 
Published: November 2014

AbstractDispersal and philopatry are fundamental processes influencing the genetic structure and persistence of populations, and might be affected by isolation and habitat perturbation. Habitat degradation induced by human activities could have detrimental consequences on the genetic structure of populations. Therefore, it is crucial to understand the role of human impact in promoting or disrupting the genetic structure. Here, we conducted a genetic analysis using 12 polymorphic microsatellite markers of 70 lesser kestrelsFalco naumannifrom 10 breeding colonies of two subpopulations inSicily (southernItaly). Genetic differentiation between the two subpopulations was negligible, and linear distances played no role in the level of genetic relatedness recorded in the two sites. Linear distances between nests also resulted in no effects on the relatedness recorded within and between colonies in the largest subpopulation. Clusters of more‐versus less‐related individuals resulted when the two‐dimensional positions of colonies (i.e., latitude and longitude) were tested as predictors of genetic proximity instead of linear distances. Specifically, analyses of colony features showed colony size and human disturbance as factors negatively affecting the relatedness among chicks from different nests. Regardless of colony size, less‐related individuals were born in colonies located in the core of the agricultural plain, where we quantified a higher level of human disturbance. In contrast, more related individuals were in colonies located in the marginal, less disturbed, agricultural area. Given the high philopatry of this species, our results are consistent with disruption of colony fidelity related to intensification of agricultural practices. We discuss the possible implications of long‐term effects of genetic variability in small and disturbed colonies on fitness and population viability.
Regulation of Vesicular Traffic at the T Cell Immune Synapse: Lessons from the Primary Cilium
Authors: Finetti Francesca , Onnis Anna , Baldari Cosima T. 
Published: November 2014

AbstractThe signals that orchestrate the process of T cell activation are coordinated at the specialized interface that forms upon contact with an antigen presenting cell displaying a specific MHC‐associated peptide ligand, known as the immune synapse. The central role of vesicular traffic in the assembly of the immune synapse has emerged only in recent years with the finding that sustained T‐cell receptor (TCR) signaling involves delivery of TCR/CD3 complexes from an intracellular pool associated with recycling endosomes. A number of receptors as well as membrane‐associated signaling mediators have since been demonstrated to exploit this process to localize to the immune synapse. Here, we will review our current understanding of the mechanisms responsible for TCR recycling, with a focus on the intraflagellar transport system, a multimolecular complex that is responsible for the assembly and function of the primary cilium which we have recently implicated in polarized endosome recycling to the immune synapse.
An in‐vivo investigation of the therapeutic effect of pulsed focused ultrasound on tumor growth
Authors: Ma C.‐M. , Chen Xiaoming , Cvetkovic Dusica , Chen Lili 
Published: November 2014

Purpose:High‐intensity focused ultrasound (HIFU) has been investigated for ablative therapy and drug enhancement for gene therapy and chemotherapy. The aim of this work is to explore the feasibility of pulsed focused ultrasound (pFUS) for cancer therapy using an in vivo animal model.Methods:A clinical HIFU system (InSightec ExAblate 2000) integrated with a 1.5 T GE MR scanner was used in this study. Suitable ultrasound parameters were investigated to perform nonthermal sonications, keeping the temperature elevation below 4 °C as measured in real time by MR thermometry. LNCaP cells (106) were injected into the prostates of male mice (n = 20). When tumors reached a diameter of about 5 mm in 3D as measured on magnetic resonance imaging (MRI), the tumor‐bearing mice (n = 8) were treated with pFUS (1 MHz frequency; 25 W acoustic power; 0.1 duty cycle; 60 s duration). A total of 4–6 sonications were used to cover the entire tumor volume under MR image guidance. The animals were allowed to survive for 4 weeks after the treatment. The tumor growth was monitored on high‐resolution (0.2 mm) MRI weekly post treatment and was compared with that of the control group (n = 12).Results:Significant tumor growth delay was observed in the tumor‐bearing mice treated with pFUS. The mean tumor volume for the pFUS treated mice remained the same 1 week after the treatment while the mean tumor volume of the control mice grew 42% over the same time. Two weeks after the pFUS treatment, the control group had a mean tumor volume 40% greater than that of the treated group. There was a greater variation in tumor volume at 4 weeks post treatment for both treated and control mice and a slightly faster tumor growth for the pFUS treated mice.Conclusions:The authors’ results demonstrated that pFUS may have a great potential for cancer therapy. Further experiments are warranted to understand the predominantly nonthermal cell killing mechanisms of pFUS and to derive optimal ultrasound parameters and fractionation schemes to maximize the therapeutic effect of pFUS.
Seasonal Training-Load Quantification in Elite English Premier League Soccer Players
Authors: Malone James J. , Di Michele Rocco , Morgans Ryland , Burgess Darren , Morton James P. , Drust Barry 
Published: November 2014

Purpose:To quantify the seasonal training load completed by professional soccer players of the English Premier League.Methods:Thirty players were sampled (using GPS, heart rate, and rating of perceived exertion [RPE]) during the daily training sessions of the 2011–12 preseason and in-season period. Preseason data were analyzed across 6 × 1-wk microcycles. In-season data were analyzed across 6 × 6-wk mesocycle blocks and 3 × 1-wk microcycles at start, midpoint, and end-time points. Data were also analyzed with respect to number of days before a match.Results:Typical daily training load (ie, total distance, high-speed distance, percent maximal heart rate [%HRmax], RPE load) did not differ during each week of the preseason phase. However, daily total distance covered was 1304 (95% CI 434–2174) m greater in the 1st mesocycle than in the 6th. %HRmax values were also greater (3.3%, 1.3−5.4%) in the 3rd mesocycle than in the first. Furthermore, training load was lower on the day before match (MD-1) than 2 (MD-2) to 5 (MD-5) d before a match, although no difference was apparent between these latter time points.Conclusions:The authors provide the 1st report of seasonal training load in elite soccer players and observed that periodization of training load was typically confined to MD-1 (regardless of mesocycle), whereas no differences were apparent during MD-2 to MD-5. Future studies should evaluate whether this loading and periodization are facilitative of optimal training adaptations and match-day performance.