bluuebunny/crossref_metadata_2025 huggingface dataset:
Respectful encounters and return to work: empirical study of long-term sick-listed patients' experiences of Swedish healthcare
Authors: Lynöe Niels , Wessel Maja , Olsson Daniel , Alexanderson Kristina , Helgesson Gert
Published: October 2011

Aims

To study long-term sick-listed patients' self-estimated ability to return to work after experiences of healthcare encounters that made them feel either respected or wronged.

Methods

A cross-sectional and questionnaire-based survey was used to study a sample of long-term sick-listed patients (n=5802 respondents). The survey included questions about positive and negative encounters as well as reactions to these encounters, such as ‘feeling respected’ and ‘feeling wronged’. The questionnaire also included questions about the effects of these encounters on the patients' ability to return to work.

Results

Among patients who had experienced positive encounters, those who also felt respected (n=3327) demonstrated significantly improved self-estimated ability to return to work compared to those who did not feel respected (n=79) (62% (95% CI 60% to 64%) vs 34% (95% CI 28% to 40%)). Among patients with experiences of negative encounters, those who in addition felt wronged (n=993) claimed to be significantly more impeded from returning to work compared to those who did not feel wronged (n=410) (50% (95% CI 47% to 53%) vs 31% (95% CI 27% to 35%)).

Conclusions

The study indicates that positive encounters in healthcare combined with feeling respected significantly facilitate sickness absentees' self-estimated ability to return to work, while negative encounters combined with feeling wronged significantly impair it.
HER2genetic heterogeneity in breast carcinoma
Authors: Öhlschlegel Christian , Zahel Katharina , Kradolfer Doris , Hell Margreth , Jochum Wolfram
Published: October 2011

Aims

To determine the frequency ofHER2genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma, and to identify clinicopathological features that characterise breast carcinomas withHER2genetic heterogeneity.

Methods

530 invasive breast carcinomas were retrospectively analysed forHER2genetic heterogeneity, and investigated for a potential association ofHER2genetic heterogeneity with otherHER2FISH findings, clinicopathological parameters, oestrogen/progesterone receptor expression and DNA cytometric parameters in breast carcinomas with an equivocal (2+) HER2 immunohistochemical score.

Results

The overall frequency ofHER2genetic heterogeneity was 14.7% in a cohort of 218 consecutive breast carcinomas.HER2genetic heterogeneity was most frequent in invasive breast carcinomas with an equivocal (2+) HER2 immunohistochemical score. Among the 151 carcinomas lackingHER2amplification, 16.1% showedHER2genetic heterogeneity. In an extended cohort of 345 carcinomas with a (2+) HER2 score, the frequency ofHER2genetic heterogeneity was 41%, and was associated with the absence ofHER2gene clusters, chromosome 17 polysomy, histological tumour grade, DNA ploidy category and 5c exceeding rate.

Conclusion

HER2genetic heterogeneity according to the ASCO/CAP definition is frequent in breast carcinoma, and is most often present in carcinomas with an equivocal (2+) HER2 score. Many carcinomas withHER2genetic heterogeneity have a negativeHER2amplification status, although they contain a significant number of tumour cells withHER2gene amplification. Single cell scoring of theHER2/17 centromeric probe (CEP17) ratio is necessary to identify carcinomas withHER2genetic heterogeneity, because they lack specific clinicopathological characteristics.
Modelling the association of disability according to the WHO International Classification of Functioning, Disability and Health (ICF) with mortality in the British Women's Heart and Health Study
Authors: Dale Caroline , Prieto-Merino David , Kuper Hannah , Adamson Joy , Bowling Ann , Ebrahim Shah , Casas Juan P
Published: October 2011

Background

The WHO International Classification of Functioning, Disability and Health (ICF) is now the dominant model for exploring the social consequences of a health condition. This paper investigates the association of the different ICF disability domains with mortality.

Methods

Data are from the British Women Heart and Health Study, a large (n=4157) prospectively studied cohort of women randomly selected from 23 towns aged 64–83 years in 2003. Scores were calculated to describe the cumulative load of impairments, limitations and restrictions within each ICF domain. Cox proportional hazards regression was used to calculate mortality HRs per unit score increase within each ICF domain. Adjustments were made for age, town, living status, socioeconomic status, lifestyle behaviours and health conditions.

Results

Each ICF domain was associated with mortality after controlling for lifestyle factors and health conditions. However, only complex activities (HR=1.09, 95% CI 1.01 to 1.18) and participation (HR=1.10, 95% CI 1.04 to 1.16) were independent predictors of mortality following adjustment for all other disability domains and potential confounders.

Conclusions

Results suggest that difficulties with complex activities or social participation could be used to identify and target women at high risk of dying. Interventions to facilitate complex activities or improve social participation may help to delay mortality in elderly women.
ENTANGLEMENT TRAPPING AND SUDDEN DEATH IN A COMMON BAND GAP
Authors: HAN FENG , ZHANG MING-HUA
Published: October 2011

Using the pseudomode method, we study the exact entanglement dynamics of two atoms in a common band gap. In order to understand the role played by the common band gap we compare our results with the case of two independent band gap model. We demonstrate that the parameter region at which the entanglement sudden death occurs is smaller than the independent band gap model. Moreover, the atomic entanglement trapping can also be achieved in the common band gap model, and the value of entanglement trapping is larger in the common band gap case than in the independent band gap case.
NEW ARBITRATED QUANTUM SIGNATURE WITH MESSAGE RECOVERY
Authors: ZHANG J.
Published: October 2011

Recently, Lee proposed two quantum signature schemes with message recovery. This paper shows insecurity in their schemes such that the scheme could be repudiated by the receiver Bob. Then, this paper proposes an arbitrated quantum signature scheme based on the correlation of Einstein–Podolsky–Rosen (EPR) pairs. Compared with Lee's scheme, the new scheme not only maintains the advantages of the original scheme but offers a higher efficiency in transmission and it can also avoid being disavowed by the receiver.
Angiotensin II increases the permeability and PV-1 expression of endothelial cells
Authors: Bodor Csaba , Nagy János Péter , Végh Borbála , Németh Adrienn , Jenei Attila , MirzaHosseini Shahrokh , Sebe Attila , Rosivall László
Published: October 2011

Angiotensin II (ANG II), the major effector molecule of the renin-angiotensin system (RAS), is a powerful vasoactive mediator associated with hypertension and renal failure. In this study the permeability changes and its morphological attributes in endothelial cells of human umbilical vein (HUVECs) were studied considering the potential regulatory role of ANG II. The effects of ANG II were compared with those of vascular endothelial growth factor (VEGF). Permeability was determined by 40 kDa FITC-Dextran and electrical impedance measurements. Plasmalemmal vesicle-1 (PV-1) mRNA levels were measured by PCR. Endothelial cell surface was studied by atomic force microscopy (AFM), and caveolae were visualized by transmission electron microscopy (TEM) in HUVEC monolayers. ANG II (10−7 M), similarly to VEGF (100 ng/ml), increased the endothelial permeability parallel with an increase in the number of cell surface openings and caveolae. AT1 and VEGF-R2 receptor blockers (candesartan and ZM-323881, respectively) blunted these effects. ANG II and VEGF increased the expression of PV-1, which could be blocked by candesartan or ZM-323881 pretreatments and by the p38 mitogem-activated protein (MAP) kinase inhibitor SB-203580. Additionally, SB-203580 blocked the increase in endothelial permeability and the number of surface openings and caveolae. In conclusion, we have demonstrated that ANG II plays a role in regulation of permeability and formation of cell surface openings through AT1 receptor and PV-1 protein synthesis in a p38 MAP kinase-dependent manner in endothelial cells. The surface openings that increase in parallel with permeability may represent transcellular channels, caveolae, or both. These morphological and permeability changes may be involved in (patho-) physiological effects of ANG II.
Static mechanical stretching accelerates lipid production in 3T3-L1 adipocytes by activating the MEK signaling pathway
Authors: Shoham Naama , Gottlieb Ruth , Sharabani-Yosef Orna , Zaretsky Uri , Benayahu Dafna , Gefen Amit
Published: October 2011

Understanding mechanotransduction in adipocytes is important for research of obesity and related diseases. We cultured 3T3-L1 preadipocytes on elastic substrata and applied static tensile strains of 12% to the substrata while inducing differentiation. Using an image processing method, we monitored lipid production for a period of 3–4 wk. The ratio of %-lipid area per field of view (FOV) in the stretched over nonstretched cultures was significantly greater than unity ( P < 0.05), reaching ∼1.8 on average starting from experimental day ∼10. The superior coverage of the FOV by lipids in the stretched cultures was due to significantly greater sizes of lipid droplets (LDs) with respect to nonstretched cultures, starting from experimental day ∼10 ( P < 0.05), and due to significantly more LDs per cell between days ∼10 and ∼17 ( P < 0.05). The statically stretched cells also differentiated significantly faster than the nonstretched cells within the first ∼10 days ( P < 0.05). Adding peroxisome proliferator-activated receptor-γ (PPARγ) antagonist did not change these trends, as the %-lipid area per FOV in the stretched cultures that received this treatment was still significantly greater than in the nonstretched cultures without the PPARγ antagonist (14.44 ± 1.96% vs. 10.21 ± 3%; P < 0.05). Hence, the accelerated adipogenesis in the stretched cultures was not mediated through PPARγ. Nonetheless, inhibiting the MEK/MAPK signaling pathway reduced the extent of adipogenesis in the stretched cultures (13.53 ± 5.63%), bringing it to the baseline level of the nonstretched cultures without the MEK inhibitor (10.21 ± 3.07%). Our results hence demonstrate that differentiation of adipocytes can be enhanced by sustained stretching, which activates the MEK signaling pathway.
Differential activation of RAGE by HMGB1 modulates neutrophil-associated NADPH oxidase activity and bacterial killing
Authors: Tadié Jean-Marc , Bae Hong-Beom , Banerjee Sami , Zmijewski Jaroslaw W. , Abraham Edward
Published: October 2011

The receptor for advanced glycation end products (RAGE) plays an important role in host defense against bacterial infection. In the present experiments, we investigated the mechanisms by which RAGE contributes to the ability of neutrophils to eradicate bacteria. Wild-type ( RAGE+/+) neutrophils demonstrated significantly greater ability to kill Eschericia coli compared with RAGE−/− neutrophils. After intraperitoneal injection of E. coli , increased numbers of bacteria were found in the peritoneal fluid from RAGE−/− as compared with RAGE+/+ mice. Exposure of neutrophils to the protypical RAGE ligand AGE resulted in activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and enhanced killing of E. coli , and intraperitoneal injection of AGE enhanced bacterial clearance during peritonitis. However, incubation of neutrophils with high mobility group box 1 protein (HMGB1), which also binds to RAGE, diminished E. coli -induced activation of NADPH oxidase in neutrophils and bacterial killing both in vitro and in vivo. Deletion of the COOH-terminal tail of HMGB1, a region necessary for binding to RAGE, abrogated the ability of HMGB1 to inhibit bacterial killing. Incubation of neutrophils with HMGB1 diminished bacterial or AGE-dependent activation of NADPH oxidase. The increase in phosphorylation of the p40phox subunit of NADPH oxidase that occurred after culture of neutrophils with E. coli was inhibited by exposure of the cells to HMGB1. These results showing that HMGB1, through RAGE-dependent mechanisms, diminishes bacterial killing by neutrophils as well as NADPH oxidase activation provide a novel mechanism by which HMGB1 can potentiate sepsis-associated organ dysfunction and mortality.
Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status
Authors: Thomas Claire , Bishop David J. , Lambert Karen , Mercier Jacques , Brooks George A.
Published: October 2011

Two lactate/proton cotransporter isoforms (monocarboxylate transporters, MCT1 and MCT4) are present in the plasma (sarcolemmal) membranes of skeletal muscle. Both isoforms are symports and are involved in both muscle pH and lactate regulation. Accordingly, sarcolemmal MCT isoform expression may play an important role in exercise performance. Acute exercise alters human MCT content, within the first 24 h from the onset of exercise. The regulation of MCT protein expression is complex after acute exercise, since there is not a simple concordance between changes in mRNA abundance and protein levels. In general, exercise produces greater increases in MCT1 than in MCT4 content. Chronic exercise also affects MCT1 and MCT4 content, regardless of the initial fitness of subjects. On the basis of cross-sectional studies, intensity would appear to be the most important factor regulating exercise-induced changes in MCT content. Regulation of skeletal muscle MCT1 and MCT4 content by a variety of stimuli inducing an elevation of lactate level (exercise, hypoxia, nutrition, metabolic perturbations) has been demonstrated. Dissociation between the regulation of MCT content and lactate transport activity has been reported in a number of studies, and changes in MCT content are more common in response to contractile activity, whereas changes in lactate transport capacity typically occur in response to changes in metabolic pathways. Muscle MCT expression is involved in, but is not the sole determinant of, muscle H+and lactate anion exchange during physical activity.
Ventricular function during exercise in mice and rats
Authors: Lujan Heidi L. , Janbaih Hussein , Feng Han-Zhong , Jin Jian-Ping , DiCarlo Stephen E.
Published: October 2011

The mouse has many advantages over other experimental models for the molecular investigation of left ventricular (LV) function. Accordingly, there is a keen interest in, as well as an intense need for, a conscious, chronically instrumented, freely moving mouse model for the determination of cardiac function. To address this need, we used a telemetry device for repeated measurements of LV function in conscious mice at rest and during exercise. For reference, we compared the responses in mice to the responses in identically instrumented conscious rats. The transmitter body of the telemetry device (rat PA-C40; mouse PA-C10; Data Sciences International, St. Paul, MN) was placed in the intraperitoneal space through a ventral abdominal approach (rat) or subcutaneously on the left flank (mouse). The pressure sensor, located within the tip of a catheter, was inserted into the left ventricle through an apical stab wound (18 gauge for rat; 21 gauge for mouse) for continuous, nontethered, recordings of pulsatile LV pressure. A minimum of 1 wk was allowed for recovery and for the animals to regain their presurgical weight. During the recovery period, the animals were handled, weighed, and acclimatized to the laboratory, treadmill, and investigators. Subsequently, LV parameters were recorded at rest and during a graded exercise test. The results document, for the first time, serial assessment of ventricular function during exercise in conscious mice and rats. This methodology may be adopted for advancing the concepts and ideas that drive cardiovascular research.
High-resolution analysis of metabolic cycles in the intertidal musselMytilus californianus
Authors: Connor Kwasi M. , Gracey Andrew Y.
Published: October 2011

Inhabitants of the marine rocky intertidal live in an environment that alternates between aquatic and terrestrial due to the rise and fall of the tide. The tide creates a cyclical availability of oxygen with animals having access to oxygenated water during episodes of submergence, while access to oxygen is restricted during aerial emergence. Here we performed liquid chromatography and gas chromatography-mass spectrometry enabled metabolomic profiling of gill samples isolated from the California ribbed mussel, Mytilus californianus, to investigate how metabolism is orchestrated in this variable environment. We created a simulated intertidal environment in which mussels were acclimated to alternating high and low tides of 6 h duration, and samples were taken every 2 h for 72 h to capture reproducible changes in metabolite levels over six high and six low tides. We quantified 169 named metabolites of which 24 metabolites cycled significantly with a 12-h period that was linked to the tidal cycle. These data confirmed the presence of alternating phases of fermentation and aerobic metabolism and highlight a role for carnitine-conjugated metabolites during the anaerobic phase of this cycle. Mussels at low tide accumulated eight carnitine-conjugated metabolites, arising from the degradation of fatty acids, branched-chain amino acids, and mitochondrial β-oxidation end products. The data also implicate sphingosine as a potential signaling molecule during aerial emergence. These findings identify new levels of metabolic control whose role in intertidal adaptation remains to be elucidated.
Speech sounds alter facial skin sensation
Authors: Ito Takayuki , Ostry David J.
Published: October 2011

Interactions between auditory and somatosensory information are relevant to the neural processing of speech since speech processes and certainly speech production involves both auditory information and inputs that arise from the muscles and tissues of the vocal tract. We previously demonstrated that somatosensory inputs associated with facial skin deformation alter the perceptual processing of speech sounds. We show here that the reverse is also true, that speech sounds alter the perception of facial somatosensory inputs. As a somatosensory task, we used a robotic device to create patterns of facial skin deformation that would normally accompany speech production. We found that the perception of the facial skin deformation was altered by speech sounds in a manner that reflects the way in which auditory and somatosensory effects are linked in speech production. The modulation of orofacial somatosensory processing by auditory inputs was specific to speech and likewise to facial skin deformation. Somatosensory judgments were not affected when the skin deformation was delivered to the forearm or palm or when the facial skin deformation accompanied nonspeech sounds. The perceptual modulation that we observed in conjunction with speech sounds shows that speech sounds specifically affect neural processing in the facial somatosensory system and suggest the involvement of the somatosensory system in both the production and perceptual processing of speech.
Mapping brain activation and information during category-specific visual working memory
Authors: Linden David E. J. , Oosterhof Nikolaas N. , Klein Christoph , Downing Paul E.
Published: October 2011

How is working memory for different visual categories supported in the brain? Do the same principles of cortical specialization that govern the initial processing and encoding of visual stimuli also apply to their short-term maintenance? We investigated these questions with a delayed discrimination paradigm for faces, bodies, flowers, and scenes and applied both univariate and multivariate analyses to functional magnetic resonance imaging (fMRI) data. Activity during encoding followed the well-known specialization in posterior areas. During the delay interval, activity shifted to frontal and parietal regions but was not specialized for category. Conversely, activity in visual areas returned to baseline during that interval but showed some evidence of category specialization on multivariate pattern analysis (MVPA). We conclude that principles of cortical activation differ between encoding and maintenance of visual material. Whereas perceptual processes rely on specialized regions in occipitotemporal cortex, maintenance involves the activation of a frontoparietal network that seems to require little specialization at the category level. We also confirm previous findings that MVPA can extract information from fMRI signals in the absence of suprathreshold activation and that such signals from visual areas can reflect the material stored in memory.
Increased nicotinic receptor desensitization in hypoglossal motor neurons following chronic developmental nicotine exposure
Authors: Pilarski Jason Q. , Wakefield Hilary E. , Fuglevand Andrew J. , Levine Richard B. , Fregosi Ralph F.
Published: October 2011

Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed on hypoglossal motor neurons (XII MNs) that innervate muscles of the tongue. Activation of XII MN nAChRs evokes depolarizing currents, which are important for regulating the size and stiffness of the upper airway. Although data show that chronic developmental nicotine exposure (DNE) blunts cholinergic neurotransmission in the XII motor nucleus, it is unclear how nAChRs are involved. Therefore, XII MN nAChR desensitization and recovery were examined in tissues from DNE or control pups using a medullary slice preparation and tight-seal whole cell patch-clamp recordings. nAChR-mediated inward currents were evoked by brief pressure pulses of nicotine or the α4β2 nAChR agonist RJR-2403. We found that, regardless of treatment, activatable nAChRs underwent desensitization, but, following DNE, nAChRs exhibited increased desensitization and delayed recovery. Similar results were produced using RJR-2403, showing that DNE influences primarily the α4β2 nAChR subtype. These results show that while some nAChRs preserve their responsiveness to acute nicotine following DNE, they more readily desensitize and recover more slowly from the desensitized state. These data provide new evidence that chronic DNE modulates XII MN nAChR function, and suggests an explanation for the association between DNE and the incidence of central and obstructive apneas.
Effects of Delta-Shaped Obstacles on the Thermal Performance of Solar Air Heater
Authors: Bekele Adisu , Mishra Manish , Dutta Sushanta
Published: October 2011

An experimental investigation has been carried out to study the effect of delta-shaped obstacles mounted on the absorber surface of an air heater duct with an aspect ratio 6 : 1 resembling the conditions close to solar air heaters. This study encompassed the Reynolds number (Re) ranging from 3400 to 27600, longitudinal pitch of the obstacle ([Formula: see text]) varied from 3/2 to 11/2, and relative obstacle height ( e/ H) varied from 0.25 to 0.75. The relative obstacle transverse pitch [Formula: see text] and the angle of attack of flow on obstacle = 90° are kept constant during the whole experimentation. By comparing the heat transfer data obtained from the obstacle-mounted duct with that of smooth duct under similar geometrical and flow conditions, the obstacle-mounted duct enhances the heat transfer by 3.6-times at Re = 7276.82, [Formula: see text], and [Formula: see text].
Morphoea with Myositis: A Rare Association
Authors: Sommerlad Mary , Bull Richard , Gorman Claire
Published: October 2011

In this case, we describe an unusual presentation of a young woman with a rash typical of morphoea (confirmed on biopsy), who went on to develop myositis in an atypical distribution. Although the association of myositis with diffuse systemic sclerosis is well described, the link with localised scleroderma (morphoea) and myositis has not been described.
Cytotoxicity Property of Nano-TiO2Sol and Nano-TiO2Powder
Authors: He Pingting , Tao Jie , Xue Jianjun , Chen Yulan
Published: October 2011

A homogeneous and transparent titania (TiO2) sol with nanosized anatase TiO2particles was prepared by hydrothermal synthesis method. The transmission electron microscope and X-ray diffraction were used to characterize the structure and morphology of particulates in the TiO2sol and purchased TiO2powder. The results show that the homogeneous anatase crystalline phase was formed and the size of the spindle-like particle in sol was about 20 nm in width and 150 nm in average length, and the particulates of the purchased powder were globular-like about 50 nm in diameter. In addition, a consistent set of in vitro experimental protocols was used to study the effects of nano-TiO2sol as prepared and nano-TiO2powder on mouse peritoneal macrophage. The cytotoxicity tests in vitro indicate that, with the increasing of TiO2sol concentration contaminated with the cells, the relative proliferation rate of macrophage cells was improved slightly after the cells contaminated for 24 h, but it reduced rapidly after contaminated for 48 h. The purchased nano-TiO2powder inhibited the growth of the cells obviously as cultivating with macrophage both for 24 h and 48 h.
Possible Linkage of SP6 Transcriptional Activity with Amelogenesis by Protein Stabilization
Authors: Utami Trianna W. , Miyoshi Keiko , Hagita Hiroko , Yanuaryska Ryna Dwi , Horiguchi Taigo , Noma Takafumi
Published: October 2011

Ameloblasts produce enamel matrix proteins such as amelogenin, ameloblastin, and amelotin during tooth development. The molecular mechanisms of ameloblast differentiation (amelogenesis) are currently not well understood. SP6 is a transcription factor of the Sp/KLF family that was recently found to regulate cell proliferation in a cell‐type‐specific manner. Sp6‐deficient mice demonstrate characteristic tooth anomalies such as delayed eruption of the incisors and supernumerary teeth with disorganized amelogenesis. However, it remains unclear how Sp6 controls amelogenesis. In this study, we used SP6 high producer cells to identify SP6 target genes. Based on the observations that long‐term culture of SP6 high producer cells reduced SP6 protein expression but not Sp6 mRNA expression, we found that SP6 is short lived and specifically degraded through a proteasome pathway. We established an in vitro inducible SP6 expression system coupled with siRNA knockdown and found a possible linkage between SP6 and amelogenesis through the regulation of amelotin and Rock1 gene expression by microarray analysis. Our findings suggest that the regulation of SP6 protein stability is one of the crucial steps in amelogenesis.
Rapid Recovery of Visual Acuity after Lumboperitoneal Shunt Operation in Malignant Idiopathic Intracranial Hypertension
Authors: Bir Levent Sinan , Degirmenci Eylem , Erdogan Cagdas , Bilgin Selma , Coşkun Erdal
Published: October 2011

Background. Idiopathic intracranial hypertension can cause rapid deterioration of visual acuity in some severe cases, and these cases are usually thought to have “malignant” form of this disease.Case. In this paper, we report on a 16-year-old girl who is a typical example for malignant idiopathic intracranial hypertension with a rapid recovery of visual acuity after lumboperitoneal shunt operation.Observations and Conclusions. Malignant form of idiopathic intracranial hypertension must be kept in mind in selected patients to avoid irreversible visual loss.
Molecular Network Associated with MITF in Skin Melanoma Development and Progression
Authors: Yajima Ichiro , Kumasaka Mayuko Y. , Thang Nguyen Dinh , Goto Yuji , Takeda Kozue , Iida Machiko , Ohgami Nobutaka , Tamura Haruka , Yamanoshita Osamu , Kawamoto Yoshiyuki , Furukawa Keiko , Kato Masashi
Published: October 2011

Various environmental and genetic factors affect the development and progression of skin cancers including melanoma. Melanoma development is initially triggered by environmental factors including ultraviolet (UV) light, and then genetic/epigenetic alterations occur in skin melanocytes. These first triggers alter the conditions of numerous genes and proteins, and they induce and/or reduce gene expression and activate and/or repress protein stability and activity, resulting in melanoma progression.Microphthalmia-associated transcription factor(MITF) is a master regulator gene of melanocyte development and differentiation and is also associated with melanoma development and progression. To find better approaches to molecular-based therapies for patients, understanding MITF function in skin melanoma development and progression is important. Here, we review the molecular networks associated with MITF in skin melanoma development and progression.
A New Reduced Stabilized Mixed Finite‐Element Method Based on Proper Orthogonal Decomposition for the Transient Navier‐Stokes Equations
Authors: Wang Aiwen , Li Jian , Di Zhenhua , Tian Xiangjun , Xie Dongxiu
Published: October 2011

A reduced stabilized mixed finite‐element (RSMFE) formulation based on proper orthogonal decomposition (POD) for the transient Navier‐Stokes equations is presented. An ensemble of snapshots is compiled from the transient solutions derived from a stabilized mixed finite‐element (SMFE) method based on two local Gauss integrations for the two‐dimensional transient Navier‐Stokes equations by using the lowest equal‐order pair of finite elements. Then, the optimal orthogonal bases are reconstructed by implementing POD techniques for the ensemble snapshots. Combining POD with the SMFE formulation, a new low‐dimensional and highly accurate SMFE method for the transient Navier‐Stokes equations is obtained. The RSMFE formulation could not only greatly reduce its degrees of freedom but also circumvent the constraint of inf‐sup stability condition. Error estimates between the SMFE solutions and the RSMFE solutions are derived. Numerical tests confirm that the errors between the RSMFE solutions and the SMFE solutions are consistent with the the theoretical results. Conclusion can be drawn that RSMFE method is feasible and efficient for solving the transient Navier‐Stokes equations.
MAP Kinases and Prostate Cancer
Authors: Rodríguez-Berriguete Gonzalo , Fraile Benito , Martínez-Onsurbe Pilar , Olmedilla Gabriel , Paniagua Ricardo , Royuela Mar
Published: October 2011

The three major mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK are signal transducers involved in a broad range of cell functions including survival, apoptosis, and cell differentiation. Whereas JNK and p38 have been generally linked to cell death and tumor suppression, ERK plays a prominent role in cell survival and tumor promotion, in response to a broad range of stimuli such as cytokines, growth factors, ultraviolet radiation, hypoxia, or pharmacological compounds. However, there is a growing body of evidence supporting that JNK and p38 also contribute to the development of a number of malignances. In this paper we focus on the involvement of the MAPK pathways in prostate cancer, including the less-known ERK5 pathway, as pro- or antitumor mediators, through their effects on apoptosis, survival, metastatic potential, and androgen-independent growth.
Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation
Authors: Falkenberg Susan Skanderup , Tarnow Inge , Guzman Alfonso , Mølgaard Per , Simonsen Henrik Toft
Published: October 2011

12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM) and collagen- (2.0 μg/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) wereBlechnum chilense(MeOH),Luma apiculata(H2O),Amomyrtus luma(DCM : MeOH 1 : 1) andCestrum parqui(DCM : MeOH 1 : 1). The platelet aggregating inhibitory effects ofA. luma(DCM : MeOH 1 : 1), andL. apiculata(H2O) were substantial and confirmed by inhibition of platelet surface activation markers.
NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity
Authors: Huang Wei-Jan , Liang Yu-Chih , Chuang Shuang-En , Chi Li-Ling , Lee Chi-Yun , Lin Chia-Wei , Chen Ai-Ling , Huang Jing-Shi , Chiu Chun-Jung , Lee Cheng-Feng , Huang Chung-Yang , Chen Chia-Nan
Published: October 2011

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1,p21(Waf1/Cip1)gene expression had markedly increased whilecyclin B1andD1gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor genep53in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activityin vitroandin vivo.
Autocrine Endothelin-3/Endothelin Receptor B Signaling Maintains Cellular and Molecular Properties of Glioblastoma Stem Cells
Authors: Liu Yue , Ye Fei , Yamada Kazunari , Tso Jonathan L. , Zhang Yibei , Nguyen David H. , Dong Qinghua , Soto Horacio , Choe Jinny , Dembo Anna , Wheeler Hayley , Eskin Ascia , Schmid Ingrid , Yong William H. , Mischel Paul S. , Cloughesy Timothy F. , Kornblum Harley I. , Nelson Stanley F. , Liau Linda M. , Tso Cho-Lea
Published: October 2011

Glioblastoma stem cells (GSC) express both radial glial cell and neural crest cell (NCC)-associated genes. We report that endothelin 3 (EDN3), an essential mitogen for NCC development and migration, is highly produced by GSCs. Serum-induced proliferative differentiation rapidly decreased EDN3 production and downregulated the expression of stemness-associated genes, and reciprocally, two glioblastoma markers, EDN1 and YKL-40 transcripts, were induced. Correspondingly, patient glioblastoma tissues express low levels of EDN3 mRNA and high levels of EDN1 and YKL-40 mRNA. Blocking EDN3/EDN receptor B (EDNRB) signaling by an EDNRB antagonist (BQ788), or EDN3 RNA interference (siRNA), leads to cell apoptosis and functional impairment of tumor sphere formation and cell spreading/migration in culture and loss of tumorigenic capacity in animals. Using exogenous EDN3 as the sole mitogen in culture does not support GSC propagation, but it can rescue GSCs from undergoing cell apoptosis. Molecular analysis by gene expression profiling revealed that most genes downregulated by EDN3/EDNRB blockade were those involved in cytoskeleton organization, pause of growth and differentiation, and DNA damage response, implicating the involvement of EDN3/EDNRB signaling in maintaining GSC migration, undifferentiation, and survival. These data suggest that autocrine EDN3/EDNRB signaling is essential for maintaining GSCs. Incorporating END3/EDNRB-targeted therapies into conventional cancer treatments may have clinical implication for the prevention of tumor recurrence. Mol Cancer Res; 9(12); 1668–85. ©2011 AACR.
Alkaline Phosphatase Is Increased in both Brain and Plasma in Alzheimer’s Disease
Authors: Vardy Emma R.L.C. , Kellett Katherine A.B. , Cocklin Sarah L. , Hooper Nigel M.
Published: October 2011

Background: Tissue non-specific alkaline phosphatase (TNAP) has been shown to promote the neurotoxicity of extracellular tau which contributes to the spread of pathology in Alzheimer’s disease (AD). Objective: To investigate changes in TNAP activity in the hippocampus in both sporadic and familial AD, and to examine whether changes in neuronal TNAP are reflected systemically by looking at changes in plasma TNAP activity in AD. Methods: We measured the activity of TNAP in the hippocampus in sporadic AD, familial AD and appropriate age-matched controls, and in an ageing series (age: 25–88 years) of brains. In addition, we measured TNAP activity in plasma from 110 AD and 110 non-demented control participants. Results: TNAP activity was significantly increased in the hippocampus in sporadic (by 56%; p = 0.038) and familial AD (by 121%; p = 0.042) compared with the age-matched controls. However, there was no correlation of TNAP activity with age. Furthermore, plasma TNAP activity was increased in AD (by 13%; p = 0.018) and inversely correlated with cognitive function (rs = –0.211; p = 0.027). Conclusion: Together, these data indicate that TNAP is increased in both sporadic and familial AD but not in the aged brain, indicating that the increase is likely a consequence of AD-associated changes in the brain. The neuronal change in TNAP is reflected in an increase in plasma TNAP in AD and is inversely correlated with cognitive function.
Venous and arterial thrombosis in dialysis patients
Authors: Ocak Gurbey , Vossen Carla , Rotmans Joris , Lijfering Willem , Rosendaal Frits , Parlevliet Karien , Krediet Ray , Boeschoten Els , Verduijn Marion , Dekker Friedo
Published: October 2011

Whether the risk of both venous and arterial thrombosis is increased in dialysis patients as compared to the general population is unknown. In addition, it is unknown which subgroups are at highest risk. Fur-thermore, it is unknown whether having a history of venous thrombosis or arterial thrombosis prior to dialysis treatment increases mortality risk. A total of 455 dialysis patients were followed for objectively verified symptomatic thrombotic events between January 1997 and June 2009. The incidence rates in dialysis patients as compared to the general population was 5.6-fold (95% CI 3.1–8.9) increased for venous thrombosis, 11.9-fold (95% CI 9.3–14.9) increased for myocardial infarction, and 8.4-fold (95% CI 5.7–11.5) increased for ischaemic stroke. The combination of haemodialysis, lowest tertile of albumin, history of venous thrombosis, and malignancy was associated with subsequent venous thrombosis. Increased age, renal vascular disease, diabetes, high cholesterol levels, history of venous thrombosis, and history of arterial thrombosis were associated with subsequent arterial thrombosis. The all-cause mortality risk was 1.9-fold (95% CI 1.1–3.3) increased for patients with a history of venous thrombosis and 1.9-fold (95% CI 1.4–2.6) increased for patients with a history of arterial thrombosis. A potential limitation of this study was that in some risk categories as-sociations with venous thrombosis did not reach statistical significance due to small numbers. In conclusion, dialysis patients have clearly elev-ated risks of venous thrombosis and arterial thrombosis and occurrence of venous thrombosis or arterial thrombosis prior to the start of dialysis is associated with an increased mortality risk.
The Effectiveness of a Primary Care–Based Pediatric Obesity Program
Authors: Dolinsky Diana H. , Armstrong Sarah C. , Walter Emmanuel B. , Kemper Alex R.
Published: October 2011

The objective of this retrospective cohort study was to evaluate the effectiveness of the Duke University Healthy Lifestyles Program (HLP), a primary care–based childhood obesity treatment program. The study population included obese 2- through 19-year-old patients who entered the HLP between October 2006 through December 2008 and who had a visit to the HLP between the sixth and eighth month after entry. Most of the 282 patients were female (57%) and non-Hispanic/non-White (61%). The median age was 11 years. At baseline, the mean body mass index standard deviation score (BMI SDS) was 2.51, and patients achieved a mean reduction in BMI SDS of 0.10 (standard deviation = 0.20). For patients with baseline and follow-up measures of comorbidities, there were improvements in blood pressure, triglycerides, total cholesterol, and insulin resistance ( P < .05). The patients in our obesity program demonstrated a small reduction in the severity of obesity. Improvements occurred in some obesity-associated comorbidities.
Biological and political identity: The identification system in Mexico
Authors: Arteaga Nelson
Published: October 2011

In 2008, following the assassination of the son of a renowned Mexican businessman, the Mexican government, social organizations, businesses and the media signed the National Agreement for Security, Justice and Legality. This body proposed the creation of a Citizen Identification Card (CIC). Converting the assassination into a ‘big event’, it has generated a ‘moral panic’ in the country, which allowed the justification to put in place mechanisms of control and population surveillance – such as the CIC. In 2009, the federal government announced the creation of an identity card with biometric elements. However, this project had an obstacle: the struggle for databases and collection of data from the Mexican population. This article analyses how the CIC project, in Mexico, has generated a debate on the implications of concentrating on an identification card, using two forms of citizen identification: biometric and territorial reference identity.
(Re-)Problematizing the Luhmannian constructivist systems approach: A Bungean intervention
Authors: Wan Poe Yu-ze
Published: October 2011

In the field of sociological theory, after the decline of Parsons’ version of structural functionalism, Niklas Luhmann’s systems theory came to be seen as the major representative of systems thinking. While Luhmann’s autopoietic systems ontology is sophisticated and deserves serious consideration, the author argues that the prevailing identification of Luhmann’s constructivist-oriented approach with the systems approach itself is problematic mainly for two reasons. First, as the works of the Argentinian-Canadian systems theorist Mario Bunge demonstrate, the systems approach can be fruitfully based on (some version of) scientific realism. Second, the adherents to Luhmann’s constructivist epistemology in sociology seldom engage in a detailed examination of the various critiques of anti-realism offered by scientific and critical realists. Drawing on the literature on philosophy of science, especially the writings of Bunge and a few leading critical realists, the author suggests that a serious Luhmannian sociologist is obligated to provide more cogent and detailed discussions on philosophy of (social) science before taking an opinionated position on epistemology.
Developing Appropriate Methods for Cost-Effectiveness Analysis of Cluster Randomized Trials
Authors: Gomes Manuel , Ng Edmond S.-W. , Grieve Richard , Nixon Richard , Carpenter James , Thompson Simon G.
Published: October 2011

Aim. Cost-effectiveness analyses (CEAs) may use data from cluster randomized trials (CRTs), where the unit of randomization is the cluster, not the individual. However, most studies use analytical methods that ignore clustering. This article compares alternative statistical methods for accommodating clustering in CEAs of CRTs. Methods. Our simulation study compared the performance of statistical methods for CEAs of CRTs with 2 treatment arms. The study considered a method that ignored clustering—seemingly unrelated regression (SUR) without a robust standard error (SE)—and 4 methods that recognized clustering—SUR and generalized estimating equations (GEEs), both with robust SE, a “2-stage” nonparametric bootstrap (TSB) with shrinkage correction, and a multilevel model (MLM). The base case assumed CRTs with moderate numbers of balanced clusters (20 per arm) and normally distributed costs. Other scenarios included CRTs with few clusters, imbalanced cluster sizes, and skewed costs. Performance was reported as bias, root mean squared error (rMSE), and confidence interval (CI) coverage for estimating incremental net benefits (INBs). We also compared the methods in a case study. Results. Each method reported low levels of bias. Without the robust SE, SUR gave poor CI coverage (base case: 0.89 v. nominal level: 0.95). The MLM and TSB performed well in each scenario (CI coverage, 0.92–0.95). With few clusters, the GEE and SUR (with robust SE) had coverage below 0.90. In the case study, the mean INBs were similar across all methods, but ignoring clustering underestimated statistical uncertainty and the value of further research. Conclusions. MLMs and the TSB are appropriate analytical methods for CEAs of CRTs with the characteristics described. SUR and GEE are not recommended for studies with few clusters.
Costs associated with outpatient, emergency room and inpatient care for migraine in the USA
Authors: Insinga Ralph P , Ng-Mak Daisy S , Hanson Mary E
Published: October 2011

Background: Data on the average US costs of an outpatient visit, emergency room (ER) visit or hospitalization for migraine are scant, with the most recent available values based on healthcare charges reported from 1994 data.

Methods: We estimated healthcare costs associated with outpatient and ER visits and inpatient hospitalizations related to migraine retrospectively obtained from the 2007 Medstat MarketScan Commercial Claims & Encounters database. Tabulated costs reflected payments from insurers, patients and other sources. All costs were adjusted to 2010 US dollars.

Results: The estimated mean cost (95% CI) for migraine-related care per outpatient visit ( N = 680,946) was $139.88 ($139.35–140.41); per ER visit ( N = 88,128) was $775.09 ($768.10–782.09); and per inpatient hospitalization ( N = 5516) was $7317.07 ($7134.96–7499.17). The most frequently coded procedures at outpatient and ER visits were subcutaneous or intra-muscular injection, and for hospitalizations was computed tomography. Estimated annual US healthcare costs in 2010 for migraine associated with: outpatient visits were $3.2 billion, ER visits were $700 million, and inpatient hospitalizations were $375 million.

Conclusions: Direct healthcare costs associated with patient visits and hospitalizations for migraine headaches have increased since previously published estimates. Further research is needed to understand the current overall healthcare cost burden per patient and within the US population.