bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of transdermal electromotive administration of verapamil and dexamethasone versus intra‐lesional injection for Peyronie's disease
Authors: Mehrsai A. R. , Namdari F. , Salavati A. , Dehghani S. , Allameh F. , Pourmand G. 
Published: October 2012

SummaryTo compare the efficacy of transdermal electromotive administration and intra‐lesional injection of verapamil plus dexamethasone for the treatment of Peyronie's disease. Patients with Peyronie's disease of less than 2‐year duration were randomized into two groups of transdermal electromotive administration and intra‐lesional injection of verapamil plus dexamethasone. During the 6‐week therapy period, a single weekly dose of 10 mg verapamil and 4 mg dexamethasone solution was administered to 30 patients in each group either by transdermal electromotive method or via the conventional injection method by a syringe connected to a 25 G needle. Evaluations of plaque length, width, and volume, penile curvature, erectile dysfunction and penile deviations were carried out before and after 1 and 3 months of the interventions. Erectile pain was reduced in the electromotive group from a mean of 5.1–1.0 in scale of 10 and from 5.4 to 3.6 in the injection group (p = 0.006). Regarding plaque length, plaque width, penile curvature plaque volume and erectile dysfunction, the electromotive administration group showed better results which, however, were not statistically significant. (p > 0.05). Transdermal electromotive drug administration yielded comparable results as against current conventional intra‐lesional injection technique and fared better in controlling erectile pain.
Evolution of testis‐specific kinases TSSK1B and TSSK2 in primates
Authors: Shang P. , Hoogerbrugge J. , Baarends W. M. , Grootegoed J. A. 
Published: October 2012

SummaryThe testis‐specific serine/threonine protein kinases TSSK1 and TSSK2 are known to be essential for male fertility, in mice. The enzymes are present in elongating spermatids, and targeted deletion of the two genes Tssk1 and Tssk2 results in dysregulation of spermiogenesis. The mouse genes are genetically closely linked, forming a Tssk1–Tssk2 tandem. In human, TSSK1 is present in the form of a pseudogene, TSSK1A, which is linked to an intact TSSK2 gene, and in the form of an intact gene, TSSK1B, which is not genetically linked to TSSK2. Studies on conservation of genes and gene function between mouse and human are relevant, to be able to use mouse models for studies on human infertility, and to evaluate possible targets for non‐hormonal contraception targeting the male. Therefore, we have performed a detailed analysis of the evolution of genes encoding TSSK1 and TSSK2 among mammals, in particular among primates. This study includes functional analysis of replacement mutation K27R in TSSK2, which is frequently observed among humans. In primates, the kinase domains of TSSK1B and TSSK2 have evolved under negative selection, reflecting the importance to maintain their kinase activity. Positive selection was observed for the C‐terminal domain of TSSK1B, which indicates that TSSK1B and TSSK2 may perform at least partly differential functions.
The Romantic Realism of Michel Foucault The Scientific Temptation
Authors: Varela Charles R. 
Published: October 2012

AbstractBeatrice Han has argued that the theories of subjection (determinism: structure) and subjectivation (freedom: agency) are the “the blind spot[s] of Foucault's work.” Furthermore, she continues, as historical and transcendental theories, respectively, Foucault left them in a state of irresolvable conflict. In the Scientific Temptation I have shown that, as a practicing researcher, Foucault encourages us to situate the theories of the subject in the context of his un‐thematized search for a metaphysics of realism, the purpose of which was to ground his complementary reach for a possibility of naturalism. In Returning to Kant I now argue that it is this fundamental feature of “Foucault's Foucault” that drives his returns to Kant, the purpose of which was to resolve the conflicting theories of the subject and thereby solve his Giddensian problem of structure and creativity. Locating the returns and their purpose in the context of my own arguments for the recovery of human agency, I argue that Foucault's attempts to solve his Giddensian problem led to two unfortunate solutions. In the first return, his resort to Baudelaire's aesthetic subject is a regression to a pre‐noumenal conception of the Kantian subject. With the second return, the reinstatement of the Kantian subject as causally empowered, minus the noumenalism, is nothing more than a reclamation of Kant's conception. I argue that only a reconstruction of Foucault's scientific realism permits us to understand that he could have moved beyond mere reclamation to the actual recovery of human agency.
The Causal Impact of Resistance: Mediating between Resistance and Internal Conversation about Resistance
Authors: Chalari Athanasia 
Published: October 2012

AbstractCurrent literature on resistance focuses on the elements of action and opposition as its main components. However, when we use the term resistance we are not necessarily referring exclusively to the active expression of opposition, but could also be referring to discussions about such events or to stimuli that may cause these acts. Thus resistance, for the purposes of this study, is perceived in terms of action, external conversation and stimuli, and it is argued that these external characteristics may be further processed through deliberation and internal conversations about resistance. An exploratory empirical study revealed inner aspects of resistance, and examined whether internal conversations about resistance could actually be experienced by agents. This article further supports the argument that, as individuals produce internal conversations about resistance, they may end by following one of the suggested options: they may keep their internal conversations unspoken, or produce a course of action related to resistance (and identified as such), or they may produce external conversations about resistance, or they may end by producing resistance that is not recognisable (to others) as such. In all these cases, internal conversations about resistance are involved and it is therefore argued that the causal impact of resistance may derive from agential processes and powers as well as from action, stimuli or external conversations related to resistance.
Alterations of the SWI/SNF chromatin remodelling subunit‐BRG1 and BRM in hepatocellular carcinoma
Authors: Endo Mio , Yasui Kohichiroh , Zen Yoh , Gen Yasuyuki , Zen Keika , Tsuji Kazuhiro , Dohi Osamu , Mitsuyoshi Hironori , Tanaka Shinji , Taniwaki Masafumi , Nakanuma Yasuni , Arii Shigeki , Yoshikawa Toshikazu 
Published: October 2012

AbstractBackgroundThe SWI/SNF chromatin remodelling complex, which contains either brahma‐related gene‐1 (BRG1) or brahma (BRM) as the catalytic ATPase, functions as a master regulator of gene expression.AimsTo examine alterations of BRG1 and BRM in hepatocellular carcinoma (HCC).MethodsWe investigated DNA copy number aberrations in human HCC cell lines using a high‐density oligonucleotide microarray. We determined DNA copy numbers and expression levels of BRG1 and BRM genes in primary HCC tumours, and conducted further searches for mutations in BRG1 and BRM genes.ResultsHomozygous deletion of the BRG1 gene was found in HCC cell line SNU398. Copy number losses of BRG1 and BRM genes were observed in 14 (26%) and 7 (13%) of 54 primary HCC tumours respectively. We found four somatic missense mutations in the BRG1 gene in two of 36 primary HCC tumours, but no mutations in BRM gene. Expression of BRM mRNA, but not BRG1 mRNA, was significantly reduced in primary HCC tumours, compared to non‐tumour tissue counterparts. Immunohistochemical analyses of non‐tumour liver tissues showed that BRM protein was expressed in hepatocytes and bile‐duct epithelial cells, whereas BRG1 protein was expressed in bile‐duct epithelial cells, but not in hepatocytes. BRM protein expression was lost in nine (22.5%) of 40 HCC tumours. Loss of BRM protein expression was significantly associated with poor overall survival.ConclusionReduced expression of BRM may contribute to the carcinogenesis of HCC. Although deletions and mutations in BRG1 gene were identified, the role of BRG1 in HCC tumourigenesis remains unclear.
The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture
Authors: Hoh Alexander , Dewerth Alexander , Vogt Fabian , Wenz Julia , Baeuerle Patrick A. , Warmann Steven W. , Fuchs Joerg , Armeanu‐Ebinger Sorin 
Published: October 2012

AbstractBackgroundChemoresistance and advanced tumour stage at time of diagnosis are the major reasons for poor treatment results in hepatoblastoma (HB) and paediatric hepatocellular carcinoma (HCC). Positive results with transplantation of liver and bone marrow revealed the impact of the immune system on the treatment of liver malignancies.AimCytotoxic‐immune‐cells‐like natural killer (NK) and T cells are major player in the defence against developing tumours. This study aimed to specifically analyse the ability of ex‐vivo expanded γδ T cells to recognise and lyse HB and HCC cell lines in coculture assays.MethodsCell viability after treatment with γδ T cells was evaluated with two HB (HUH6 and HepT1) and one HCC cell line (HC‐AFW1) using a MTT‐based cytotoxicity assay. The binding of T cells to target cells was monitored using immunofluorescence microscopy.ResultsIncubation of hepatic tumour cell lines with γδ T cells led to a significant decrease in tumour cell viability. This was enhanced by zoledronic acid and histone deacetylase inhibitors. MT110, an EpCAM/CD3‐bispecific BiTE antibody could bluntly enhance tumour cell lysis close to completion. γδ T cells efficiently interacted with HB and HCC cells in a spheroid culture model.ConclusionBispecific antibodies such as MT110 might be used to intensify the antitumoural effect of γδ T cells in context of adoptive immune cell transfer. Optimised immunotherapeutic strategies might therefore improve the outcome of high risk hepatoblastoma and hepatocellular carcinoma.
OnobotulinumtoxinA Has No Effects on Growth of LNCaP and PC3 Human Prostate Cancer Cells
Authors: CHENG Yuan‐Tso , CHUNG Yueh‐Hua , KANG Hong‐Yo , TAI Ming‐Hong , CHANCELLOR Michael B. , CHUANG Yao‐Chi 
Published: October 2012

Objectives: Intraprostatic injection of botulinum toxin (BTX) has been reported to have therapeutic effects on lower urinary tract symptoms related to benign prostate hyperplasia (BPH). Patients with BPH are at risk of having prostate cancer. The present study was conducted to assess the effect of onobotulinumtoxinA on prostate cancer in vitro and in vivo.Methods: Human prostate cancer cell lines, LNCaP and PC3 were exposed to different doses of onobotulinumtoxinA (0–10 U; Allergan, Irvine, CA, USA). Cell viability, DNA fragmentation and apoptosis assay were subsequently measured. For the in vivo study, LNCaP and PC3 xenografts were introduced into nude mice and treated with intra‐tumoral onobotulinumtoxinA or saline injection. Tumor volume, histopathology and apoptosis were assessed. Presence of SNAP‐25 protein, the molecular target of onobotulinumtoxinA, was studied in both cell lines by Western blot analysis.Results: OnobotulinumtoxinA did not significantly affect cell proliferation or apoptosis in LNCaP and PC3 cells. There was no significant difference in tumor size and histopathological findings between the experimental and control groups. There was no detectable SNAP‐25 protein in both cell lines.Conclusion: OnobotulinumtoxinA does not affect the growth of LNCaP or PC3 cells in vitro and in vivo or produce significant anti‐tumor effects. Intraprostatic BTX injection for BPH might not affect the growth of prostate cancer.
Spatial and temporal patterns of genetic variation in the widespread antitropical deep‐sea coral Paragorgia arborea
Authors: Herrera S. , Shank T. M. , Sánchez J. A. 
Published: October 2012

AbstractNumerous deep‐sea species have apparent widespread and discontinuous distributions. Many of these are important foundation species, structuring hard‐bottom benthic ecosystems. Theoretically, differences in the genetic composition of their populations vary geographically and with depth. Previous studies have examined the genetic diversity of some of these taxa in a regional context, suggesting that genetic differentiation does not occur at scales of discrete features such as seamounts or canyons, but at larger scales (e.g. ocean basins). However, to date, few studies have evaluated such diversity throughout the known distribution of a putative deep‐sea species. We utilized sequences from seven mitochondrial gene regions and nuclear genetic variants of the deep‐sea coral Paragorgia arborea in a phylogeographic context to examine the global patterns of genetic variation and their possible correlation with the spatial variables of geographic position and depth. We also examined the compatibility of this morphospecies with the genealogical‐phylospecies concept by examining specimens collected worldwide. We show that the morphospecies P. arborea can be defined as a genealogical‐phylospecies, in contrast to the hypothesis that P. arborea represents a cryptic species complex. Genetic variation is correlated with geographic location at the basin‐scale level, but not with depth. Additionally, we present a phylogeographic hypothesis in which P. arborea originates from the North Pacific, followed by colonization of the Southern Hemisphere prior to migration to the North Atlantic. This hypothesis is consistent with the latest ocean circulation model for the Miocene.
Perceptions of patient education during hospital visit – described by school‐age children with a chronic illness and their parents
Authors: Kelo Marjatta , Eriksson Elina , Eriksson Ilse 
Published: October 2012

BackgroundFamilies having a child with a chronic disease face changes in their everyday lives, and the whole family is involved in patient education. Nurses bear a great responsibility for patient education, but their school‐age patients’ and their parents’ perceptions of patient education have only been studied to a limited extent.AimThe current study aimed to explore the elements of significant patient education events during a hospital visit described by school‐age children with a chronic illness and their parents.MethodThe design was qualitative and descriptive. A total of nineteen Finnish parents and their 12 children aged 5–12, suffering from chronic diseases, were interviewed using a critical incident technique. The data were analysed by deductive content analysis.FindingsThe descriptions of patient education comprised cases with parents’ shock at the outset of the patient education sessions and cases with the outcome of these sessions, including an experience of empowerment or lack of it. The patient education practices were examined by determining nursing, didactic and interpersonal competences. Nursing competence involved illustrations of knowledge and the ability to care for children and families as well as knowledge of the disease and its management. Didactic competence comprised practical examples of knowledge of teaching and the ability to implement the education process. Interpersonal competence manifested itself in the ability to have a dialogue.ConclusionThe findings show the importance of comprehensive patient education competence required of nurses giving education to families having children with chronic illnesses. This knowledge can be applied to promote nurses’ professional training and to develop patient education.
Aberrant sodium channel activity in the complex seizure disorder of Celf4 mutant mice
Authors: Sun Wenzhi , Wagnon Jacy L. , Mahaffey Connie L. , Briese Michael , Ule Jernej , Frankel Wayne N. 
Published: October 2012

Key points
Inappropriate electrochemical signalling between neurons is a central problem in epilepsy. Only a fraction of all heritable epilepsies are solved, and many are due to ion channel mutations.
Ion channels are cell surface molecules that initiate and coordinate electrochemical signalling, by allowing the right combination of ions to flow in and out of a neuron.
Ion channels may be regulated by other genes. We recently determined that the RNA‐binding protein, ‘CELF4’, affects expression of many molecules, including ion channels, to coordinate electrochemical signalling.
Here we conclude that a sodium channel called Nav1.6 is the primary instigator of abnormal excitation when CELF4 is impaired.
Nav1.6 expression is increased in the axon initial segment – a part of the neuron that initiates electrical activity – altering intrinsic excitability. We surmise that in a brain that already has difficulty regulating other molecules due to CELF4 deficiency, this leads to uncontrolled network excitation and seizures.
Abstract  Mice deficient for CELF4, a neuronal RNA‐binding protein, have a complex seizure disorder that includes both convulsive and non‐convulsive seizures, and is dependent upon Celf4 gene dosage and mouse strain background. It was previously shown that Celf4 is expressed predominantly in excitatory neurons, and that deficiency results in abnormal excitatory synaptic neurotransmission. To examine the physiological and molecular basis of this, we studied Celf4‐deficient neurons in brain slices. Assessment of intrinsic properties of layer V cortical pyramidal neurons showed that neurons from mutant heterozygotes and homozygotes have a lower action potential (AP) initiation threshold and a larger AP gain when compared with wild‐type neurons. Celf4 mutant neurons also demonstrate an increase in persistent sodium current (INaP) and a hyperpolarizing shift in the voltage dependence of activation. As part of a related study, we find that CELF4 directly binds Scn8a mRNA, encoding sodium channel Nav1.6, the primary instigator of AP at the axon initial segment (AIS) and the main carrier of INaP. In the present study we find that CELF4 deficiency results in a dramatic elevation in the expression of Nav1.6 protein at the AIS in both null and heterozygous neurons. Together these results suggest that activation of Nav1.6 plays a crucial role in seizure generation in this complex model of neurological disease.
Astrocytic GABA transporter GAT‐1 dysfunction in experimental absence seizures
Authors: Pirttimaki Tiina , Parri H. Rheinallt , Crunelli Vincenzo 
Published: October 2012

Key points
Enhanced thalamic tonic GABA inhibition plays a role in experimental absence seizures.
In this study we investigated astrocytic GABA transporter function and gliotransmitter release in an absence seizure rat model.
GAT‐1 GABA transporter currents in thalamic astrocytes were reduced in an absence seizure rat model.
Spontaneous phasic astrocytic GABA events displayed kinetic differences between absence seizure model rats and non‐epileptic controls.
Spontaneous phasic astrocyte glutamate release was not different in absence seizure model rats and non‐epileptic controls.
Abstract  An enhanced tonic GABAA inhibition in the thalamus plays a crucial role in experimental absence seizures and has been attributed, on the basis of indirect evidence, to a dysfunction of the astrocytic GABA transporter‐1 (GAT‐1). Here, the GABA transporter current was directly investigated in thalamic astrocytes from a well‐established genetic model of absence seizures, the genetic absence epilepsy rats from Strasbourg (GAERS), and its non‐epileptic control (NEC) strain. We also characterized the novel form of GABAergic and glutamatergic astrocyte‐to‐neuron signalling by recording slow outward currents (SOCs) and slow inward currents (SICs), respectively, in thalamocortical (TC) neurons of both strains. In patch‐clamped astrocytes, the GABA transporter current was abolished by combined application of the selective GAT‐1 and GAT‐3 blocker, NO711 (30 μm) and SNAP5114 (60 μm), respectively, to GAERS and NEC thalamic slices. NO711 alone significantly reduced (41%) the transporter current in NEC, but had no effect in GAERS. SNAP5114 alone reduced by half the GABA transporter current in NEC, whilst it abolished it in GAERS. SIC properties did not differ between GAERS and NEC TC neurons, whilst moderate changes in SOC amplitude and kinetics were observed. These data provide the first direct demonstration of a malfunction of the astrocytic thalamic GAT‐1 transporter in absence epilepsy and support an abnormal astrocytic modulation of thalamic ambient GABA levels. Moreover, while the glutamatergic astrocyte–neuron signalling is unaltered in the GAERS thalamus, the changes in some properties of the GABAergic astrocyte–neuron signalling in this epileptic strain may contribute to the generation of absence seizures.
Molecular characterization of theblaKPC-2gene in clinical isolates of carbapenem-resistantKlebsiella pneumoniaefrom the pediatric wards of a Chinese hospital
Authors: Liu Yang , Li Xiang-Yang , Wan La-Gen , Jiang Wei-Yan , Li Fang-Qu , Yang Jing-Hong 
Published: October 2012

The present study was conducted to confirm the presence of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae associated with a nosocomial outbreak in a Chinese pediatric hospital. From July 2009 to January 2011, 124 nonduplicated K. pneumoniae isolates were collected from specimens from patients of pediatric units in the hospital. Twelve of the 124 isolates possessed the blaKPC-2gene and showed 7 different pulsed-field gel electrophoresis (PFGE) patterns. Meanwhile, 16S rRNA methylase, acc(6′)-Ib-cr, and several types of β-lactamases were also produced by the majority of the KPC-producing isolates. Class 1 integron-encoded intI1 integrase gene was subsequently found in all strains, and amplification, sequencing, and comparison of DNA between 5′ conserved segment and 3′ conserved segment region showed the presence of several known antibiotic resistance gene cassettes of various sizes. The conjugation and plasmid-curing experiments indicated some KPC-2-encoding genes were transmissible. In addition, conjugal cotransfer of multidrug-resistant phenotypes with KPC-positive phenotypes was observed in KPC-producing strains. Restriction endonuclease analysis and DNA hybridization with a KPC-specific probe showed that the blaKPC-2gene was carried by plasmid DNA from K. pneumoniae of PFGE pattern B. The overall results indicate that the emergence and outbreak of KPC-producing K. pneumoniae in our pediatric wards occurred in conjunction with plasmids coharboring 16S rRNA methylase and extended-spectrum β-lactamases.