bluuebunny/crossref_metadata_2025 huggingface dataset:
Migration induced by epidermal and hepatocyte growth factors in oral squamous carcinoma cells in vitro: role of MEK/ERK, p38 and PI‐3 kinase/Akt
Authors: Brusevold Ingvild J. , Aasrum Monica , Bryne Magne , Christoffersen Thoralf
Published: March 2012

J Oral Pathol Med (2012) 41: 547–558

Background:  Cell migration is a necessary part of malignant invasiveness. Oral squamous cell carcinomas (OSCC) have a great tendency for local invasive growth. We have investigated signalling pathways involved in cell migration induced by epidermal growth factor (EGF) and hepatocyte growth factor (HGF) in OSCC cells and examined the effects of various experimental and clinically approved anti‐tumour signal inhibitors on the migratory activity.

Methods:  Migration was studied in three human OSCC cell lines, using a scratch wound assay in vitro and time‐lapse cinematography. Specific phosphorylation of signalling proteins was assessed by Western blotting.

Results:  In the E10 cell line, EGF and HGF induced phosphorylation of EGF receptor (EGFR) and Met, respectively, phosphorylation of ERK1/2, p38 and Akt, and dose‐dependent activation of cell migration. Addition of the EGFR‐specific inhibitors cetuximab (antibody) or gefitinib (tyrosine kinase blocker) abolished cell migration elicited by EGF. Similarly, a Met kinase inhibitor (SU11274) blocked HGF‐induced cell migration. Furthermore, when three cell lines were treated with blockers of the MEK/ERK, p38 or the PI‐3 kinase/Akt pathways, the migratory response to both EGF and HGF was inhibited, but to varying degrees. Notably, in E10 and D12 cells, HGF‐induced migration was particularly sensitive to PI‐3 K‐inhibition, while in C12 cells, both HGF‐ and EGF‐induced migration were highly sensitive to p38‐blockade.

Conclusion:  The results demonstrate that the MEK/ERK, p38 and PI‐3 kinase pathways are all involved in mediating the increased migration in OSCC cell lines induced by EGF and HGF, but their relative importance and the effects of specific signal inhibitors differ.
The machine body metaphor: From science and technology to physical education and sport, in France (1825–1935)
Authors: Gleyse J.
Published: March 2012

The long history of the conception of physical exercise in France may be viewed as a function of a series of changes in understanding the body. Scientific concepts were used to present the body in official texts by authors specializing in the subject, or to describe them, as did Michel Foucault, as epistemic changes. A departure occurred during the 19th century that is clearly demonstrated in the writings of Gustave Adolphe Hirn. This breakthrough concerned the idea of considering the organism as an energy‐generating machine. This metaphor was employed in describing the body during physical exercise from the 17th to the 19th centuries, when the body was thought of as mechanical. Such metaphors were used by the most relevant figures writing at the end of the 19th century in the rationale that is examined in this paper. It shows how Hirn, Marey, Lagrange, Demenij, Hebert, and Tissié saw the body and how they employed machine metaphors when referring to it. These machine metaphors are analyzed from the time of their scientific and technological origins up to their current use in physical and sports education. This analysis will contribute to the understanding of how a scientific metaphor comes to be in common use and may lead to particular exercise practices.
Divergent physiological characteristics and responses to endurance training among inbred mouse strains
Authors: Kilikevicius A. , Venckunas T. , Zelniene R. , Carroll A.M. , Lionikaite S. , Ratkevicius A. , Lionikas A.
Published: March 2012

Both baseline values and adaptive changes in mice can vary depending on the genetic background. We aimed to assess variation in a battery of variables and their adaptations to endurance training in six inbred mouse strains.

Males, n = 184, from A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, and PWD/PhJ strains were assigned to a control or an endurance group (5 weeks swimming exercise). Enzyme activity, histology of soleus (SOL) muscle, swimming endurance, cardiac ventricular and hind limb muscle weight, and femur length were examined.

Endurance capacity, morphological and histological variables, and enzyme activity substantially differed among strains. For example, SOL weight was twofold higher and cross‐sectional area (CSA) of fibers was ∼30% greater in C57BL/6J than in PWD/PhJ strain. The CSA of type 1 fibers were larger than type 2A in PWD/PhJ (P < 0.01); however, the reverse was true in DBA/2J and BALB/cByJ strains (P < 0.05). Swimming endurance in DBA/2J strain was ∼9 times better than in BALB/cByJ. Endurance training increased the activity of citrate synthase in gastrocnemius across strains (P < 0.01), however, changes in endurance were strain‐specific; the C57BL/6J and DBA/2J strains improved substantially, whereas A/J and BALB/cByJ strains did not.

In conclusion, genetic background is a potent determinant of the physiological characteristics and adaptations to training in mice.
Trends and distribution of oral and pharyngeal lymphoma in Israel
Authors: Zini A , Atia‐Joachim D , Sgan–Cohen HD , Lavie D , Czerninski R
Published: March 2012

Oral Diseases (2012) 18, 700–706

Objectives:  To describe the distribution and trends of oral and pharyngeal lymphoma cases in Israel.

Methods:  Incidence rates were derived from the Israel National Cancer Registry and included all registered data from 1970 to 2006. Oral lymphoma included the tongue, mouth, salivary glands, tonsils, and pharynx. Morphological description was according to WHO classification of lymphoid neoplasms.

Results:  A total of 670 cases were diagnosed, mean age 59.5 years, half were over 65 years old. Tonsils were the most prevalent site of involvement (36.0%), followed by the pharyngeal region and salivary glands. Over the years, the prevalence of lymphoma in salivary glands increased by 49%, whereas in tonsils lymphoma decreased by 28.6%. The overall 5‐year survival rate was 57% with best rates among young people.

Conclusion:  The correlation of survival, type of lymphoma and age, was similar to extra‐oral lymphoma. A trend of increased cases in the parotid region, dissimilar to other oral sites, raises a question of possible external factors or an increase in autoimmune diseases. Head and neck clinicians should be aware of different sites, types, and prognoses for the different age groups.
Production of bacteriocin by Leuconostoc mesenteroides 406 isolated from Mongolian fermented mare's milk, airag
Authors: WULIJIDELIGEN  , ASAHINA Takayuki , HARA Kazushi , ARAKAWA Kensuke , NAKANO Hiroyuki , MIYAMOTO Taku
Published: March 2012

The purification and characterization of a bacteriocin produced by Leuconostoc mesenteroides strain 406 that was isolated from traditional Mongolian fermented mare's milk, airag, were carried out. Leuconostoc mesenteroides strain 406 was identified on the basis of its morphological and biochemical characteristics and carbohydrate fermentation profile and by API 50 CH kit and 16S ribosomal DNA analyses. The neutral‐pH cell‐free supernatant of this bacterium inhibited the growth of several lactic acid bacteria and food spoilage and pathogenic organisms, including Listeria monocytogenes and Clostridium botulinum. The bacteriocin was heat‐stable and not sensitive to acid and alkaline conditions, but was sensitive to several proteolytic enzymes such as pepsin, pronase E, proteinase K, trypsin, and α‐chymotrypsin, but not catalase. Optimum bacteriocin production (4000 activity units/mL) was achieved when the strain was cultured at 25°C for 24–36 h in Man Rogosa Sharpe medium. The bacteriocin was partially purified by ammonium sulfate precipitation (80% saturation), dialysis (cut‐off MW: 1000), and gel filtration chromatography. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis revealed that the bacteriocin had a molecular weight of approximately 3.3 kDa. To our knowledge, this is the first report of the isolation of a bacteriocin‐producing Leuconostoc strain from airag. An application to fermented milks would be desired.
Students' Perceived Parental School Behavior Expectations and Their Academic Performance: A Longitudinal Analysis
Authors: Bowen Gary L. , Hopson Laura M. , Rose Roderick A. , Glennie Elizabeth J.
Published: March 2012

Self‐report data from 2,088 sixth‐grade students in 11 middle schools in North Carolina were combined with administrative data on their eighth‐grade end‐of‐the‐year achievement scores in math and reading to examine the influence of students' perceived parental school behavior expectations on their academic performance. Through use of multilevel modeling and control for the influence of students' demographics, trouble avoidance, and perceived support from adults and peers, we found that students' perceptions of their parents' expectations of their school behavior had a small but positive and statistically significant influence on their math and reading scores approximately 3 years later. Implications for the implementation of evidence‐based interventions in schools are discussed.
Family Economic Hardship and Progression of Poor Mental Health in Middle‐Aged Husbands and Wives
Authors: Wickrama K. A. S. , Surjadi Florensia F. , Lorenz Frederick O. , Conger Rand D. , O’Neal Catherine Walker
Published: March 2012

Using prospective data from 370 middle‐aged husbands and wives during a 12‐year period, we investigated the intra‐individual and dyadic influence of family economic hardship on the levels of depressive symptoms of husbands and wives over their middle years. The results suggest that family economic hardship during the early middle years contributes to a subsequent increase in depressive symptoms of husbands and wives. Consistent with stress‐process theory, economic hardship influences depressive symptoms directly and indirectly through its influence on self‐esteem. The results also provided evidence for the scar hypothesis, which suggests that depression predicts subsequent level of self‐esteem and forms a reciprocal process between depressive symptoms and self‐esteem over time. In sum, for both husbands and wives, our findings showed that depressive symptoms progress over the middle years through a self‐perpetuating reciprocal process between self‐esteem and depression initiated by early family economic hardship and through cross‐spouse influences involving self‐esteem and depressive symptoms.
Family Distance Regulation and School Engagement in Middle‐School‐Aged Children
Authors: Bartle‐Haring Suzanne , Younkin Felisha Lotspeich , Day Randal
Published: March 2012

The purpose of this study was to explore how family distance regulation and other family demographic factors influence parenting behavior and family routines, which, in turn, influences the child's school engagement. The data from the project came from a larger study conducted in a large Northwestern urban area and included both two‐parent and single‐parent families. These two family structures were compared in order to emphasize that it is the foundational family process of family distance regulation that supports other parenting practices as well as chronic stress that leads to school engagement regardless of the number of parents in the household. Implications for practice and the results of this study in relation to previous literature are discussed.
Response to three essays on The Intellectual Culture of Puritan Women, 1558–1680 presented at Renaissance Society of America Convention, April 2010  Literature Compass Conference Cluster
Authors: Lake Peter
Published: March 2012

This article considers how hard it has proven to recover the ways in which puritan religion both enabled and contained the efforts of various early modern women to combine the fulfillment of their calling as Christians with the demands placed upon them by contemporary gender roles. The article then goes on to discuss how the three essays to which it responds successfully explore the subtly contradictory nature of the impact of puritanism on the literary, intellectual and spiritual activities of godly women in early modern England.
Glass Additive Influence on the Sintering Behaviors, Magnetic and Electric Properties of Bi–Zn Co‐Doped Co2Y Ferrites
Authors: Hsiang Hsing‐I , Mei Li‐Then , Hsi Chi‐Shiung , Wu Wei‐Cheng , Wu Jer‐Hao , Yen Fu‐Su
Published: March 2012

The Bi2O3–B2O3–ZnO–SiO2 (BB35SZ) glass effects on the sintering behavior and magnetic properties of Bi–Zn co‐doped Co2Y ferrites were investigated in developing low‐temperature‐fired ferrites. The results indicate that BB35SZ glass can be used as a sintering aid to reduce the densification temperature of Co2Y ferrites from 1300°C to 900°C. The 2(Ba0.9Bi0.1O)·2(Zn0.4Co0.4Cu0.2O)·6(Fe1.97Zn0.03O3) ferrite with 4 wt% BB35SZ glass can be densified below 900°C, exhibiting an initial permeability of 3.4 and quality factor of 55. This process provides a promising candidate for multilayer chip magnetic devices for microwave applications.
Erosion Behavior of C/SiC Composites in Atomic Oxygen
Authors: Liu Xiaochong , Cheng Laifei , Zhang Litong , Yin Xiaowei , Dong Ning , Zhao Donglin , Hong Zhiliang , Li Zhonghua
Published: March 2012

A T300 carbon fiber and a SiC‐coated C/SiC composite made from the same fiber were studied in atomic oxygen environment. The carbon fiber shows significant degradation while the erosion rate of SiC‐coating of C/SiC is about 50 times lower. Evidence shows that Si is preferentially etched from the SiC surface. And XPS information showed that amorphous carbon and diamond‐like carbonare periodically generated on the tested composite surface. Statistical analysis shows that the C/SiC specimens have no significant change in flexural properties after 1‐year fluence AO treatment.
Electrical Properties of Mn3−xCoxO4 (0 ≤ x ≤ 3) Ceramics: An Interesting System for Negative Temperature Coefficient Thermistors
Authors: Rousset A. , Tenailleau C. , Dufour P. , Bordeneuve H. , Pasquet I. , Guillemet‐Fritsch S. , Poulain V. , Schuurman S.
Published: March 2012

Single‐phase spinel manganese cobalt oxides Mn3−xCoxO4 dense ceramics were prepared for the first time and their structural/electrical property relationships characterized. The electrical properties, that is, the resistivity at 25°C, the energetic constant, and the resistance drift at 125°C, were determined and correlated with the cation distribution. Finally, the electrical characteristics of the Mn3−xCoxO4 system were compare'd with other important classes of manganese‐based spinel oxides, Mn3−xNixO4 and Mn3−xCuxO4, already commercialized as negative temperature coefficient (NTC) thermistors. The high values of energetic constant and low resistivities observed in Mn3−xCoxO4 ceramics present a promising interest for such industrial applications.
Sintering and Crystallization of Phosphate Glasses by CO2‐Laser Irradiation on Hydroxyapatite Ceramics
Authors: Obata Akiko , Jones Julian D.C. , Shinya Akiyoshi , Kasuga Toshihiro
Published: March 2012

Phosphate glasses in the 50CaO‐(50‐x) P2O5‐xTiO2‐1Al2O3 (x = 5–25 mol%) system were produced and irradiated with low energy density CO2 laser to melt and crystallize on a hydroxyapatite (HA) ceramic plate for dental filler applications. The laser with 10.6 μm of wavelength is easily absorbed by phosphate and hydroxy groups. The phosphate glasses containing ~15 mol% of titania strongly adhered to the HA plate surface through melting and sintering by the laser irradiation. The coatings after the laser irradiation contained crystalline phases. There was no significant changes in the morphology of the coating containing 15 mol% of TiO2 on the HA plate even after soaking in 0.1 mM HCl solution for 10 min. This coating was suspected to have good chemical durability. Powders of the glass or glass‐ceramic containing 15 mol% of TiO2 were soaked in distilled water to check their dissolution behavior over the long term. Dissolution from the glass‐ceramic was much slower than those from the glass at all points.
Do Animals Engage in Conceptual Thought?
Authors: Beck Jacob
Published: March 2012

This article surveys and evaluates the answers that philosophers and animal researchers have given to two questions. Do animals have thoughts? If so, are their thoughts conceptual? Along the way, special attention is paid to distinguish debates of substance from mere battles over terminology, and to isolate fruitful areas for future research.
Time and Personal Identity in Nietzsche’s Theory of Eternal Recurrence
Authors: Jenkins Scott
Published: March 2012

Friedrich Nietzsche’s theory of eternal recurrence is an essential part of his mature philosophy, but the theory’s metaphysical commitments and practical implications are both obscure. In this essay I consider only the metaphysical elements of the theory, with the aim of determining whether it is possible that we live our lives infinitely many times, as the theory maintains. I argue that the possibility of eternal recurrence turns on issues in personal identity and the metaphysics of time. As I proceed, I also consider the relation between Nietzsche’s theory of eternal recurrence and theories of recurrence found in the work of Heraclitus, the Pythagoreans, and the Stoics.
Isolation and initial characterization of a novel type of Baeyer–Villiger monooxygenase activity from a marine microorganism
Authors: Willetts Andrew , Joint Ian , Gilbert Jack A. , Trimble William , Mühling Martin
Published: March 2012

A novel type of Baeyer–Villiger monooxygenase (BVMO) has been found in a marine strain of Stenotrophomonas maltophila strain PML168 that was isolated from a temperate intertidal zone. The enzyme is able to use NADH as the source of reducing power necessary to accept the atom of diatomic oxygen not incorporated into the oxyfunctionalized substrate. Growth studies have establish that the enzyme is inducible, appears to serve a catabolic role, and is specifically induced by one or more unidentified components of seawater as well as various anthropogenic xenobiotic compounds. A blast search of the primary sequence of the enzyme, recovered from the genomic sequence of the isolate, has placed this atypical BVMO in the context of the several hundred known members of the flavoprotein monooxygenase superfamily. A particular feature of this BVMO lies in its truncated C‐terminal domain, which results in a relatively small protein (357 amino acids; 38.4 kDa). In addition, metagenomic screening has been conducted on DNA recovered from an extensive range of marine environmental samples to gauge the relative abundance and distribution of similar enzymes within the global marine microbial community. Although low, abundance was detected in samples from many marine provinces, confirming the potential for biodiscovery in marine microorganisms.
Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus
Authors: Balasubramanian Sivaraman Arumugam , Mohan Sujatha , Pye David Cecil , Willcox Mark Duncan Perry
Published: March 2012

Purpose:  To investigate the expression of proteases, proteolytic activity and cytokines in the tear film of people with keratoconus.

Methods:  Basal tears from people with keratoconus, from individuals who had undergone corneal collagen cross‐linking for the treatment of keratoconus, and from normal controls were collected using a capillary tube. Corneal curvature of each subject was mapped. The total protein in tears was estimated. Levels and activity of proteases in the tears were analysed using specific antibody arrays and activity assays.

Results:  The total tear protein level was significantly reduced in keratoconus (4.1 ± 0.9 mg/ml) compared with normals (6.7 ± 1.4 mg/ml) (p < 0.0001) or subjects who had undergone corneal collagen cross‐linking (5.7 ± 2.3 mg/ml) (p < 0.005). Significantly (p < 0.05) increased tear expression of matrix metalloproteinases (MMP) ‐1, ‐3, ‐7, ‐13, interleukins (IL) ‐4, ‐5, ‐6, ‐8 and tumour necrosis factor (TNF) ‐α, ‐β were evident in keratoconus. Tear IL‐6 was the only cytokine significantly (p < 0.05) increased in tears of keratoconus subjects compared with the collagen cross‐linked group. No significant difference in tear proteases were observed between the normal and the cross‐linked groups, although the expression of TNF‐α was significantly (p < 0.05) increased in the cross‐linked group compared with the controls. Elevated gelatinolytic (87.5 ± 33.6 versus 45.8 ± 24.6 FIU, p < 0.0001) and collagenolytic (6.1 ± 3.2 versus 3.6 ± 2.0 FIU, p < 0.05) activities were observed in tears from keratoconus compared with normal subjects. The activity of tear gelatinases (69.6 ± 22.2 FIU) and collagenases (5.7 ± 3.3 FIU) in the collagen cross‐linked group was not significantly different compared with either keratoconus or normals.

Conclusion:  Tears of people with keratoconus had 1.9 times higher levels of proteolytic activity and over expression of several MMPs and cytokines compared with tears from controls. Further investigations are required to study the possible implications of these changes and whether they can be used to monitor disease progression or determine the success of corneal collagen cross‐linking.
Rhododendron aureodorsale (Ericaceae) comb. nov. from southwestern Shaanxi, China
Authors: Ma Yong‐Peng , Nielsen Jens , Li Nai‐Wei , Sun Wei‐Bang
Published: March 2012

In this paper, we propose that Rhododendron clementinae Forrest ex W. W. Sm. subsp. aureodorsale W. P. Fang ex J. Q. Fu should be recognized at species rank as Rhododendron aureodorsale (W. P. Fang ex J. Q. Fu) Y. P. Ma & J. Nielsen. This species is similar to R. clementinae, but has an isolated distribution range, and differs by having tawny indumentum without pellicle on the abaxial leaf surface, sparse hairs on both pedicel and sepals, and always 7 corolla lobes.
Impact of nitrogen allocation on growth and photosynthesis of Miscanthus (Miscanthus × giganteus)
Authors: Wang Dan , Maughan Mathew W. , Sun Jindong , Feng Xiaohui , Miguez Fernando , Lee DoKyoung , Dietze Michael C.
Published: March 2012

Nitrogen (N) addition typically increases overall plant growth, but the nature of this response depends upon patterns of plant nitrogen allocation that vary throughout the growing season and depend upon canopy position. In this study seasonal variations in leaf traits were investigated across a canopy profile in Miscanthus (Miscanthus × giganteus) under two N treatments (0 and 224 kg ha−1) to determine whether the growth response of Miscanthus to N fertilization was related to the response of photosynthetic capacity and nitrogen allocation. Miscanthus yielded 24.1 Mg ha−1 in fertilized plots, a 40% increase compared to control plots. Photosynthetic properties, such as net photosynthesis (A), maximum rate of rubisco carboxylation (Vcmax), stomatal conductance (gs) and PSII efficiency (Fv'/Fm'), all decreased significantly from the top of the canopy to the bottom, but were not affected by N fertilization. N fertilization increased specific leaf area (SLA) and leaf area index (LAI). Leaf N concentration in different canopy layers was increased by N fertilization and the distribution of N concentration within canopy followed irradiance gradients. These results show that the positive effect of N fertilization on the yield of Miscanthus was unrelated to changes in photosynthetic rates but was achieved mainly by increased canopy leaf area. Vertical measurements through the canopy demonstrated that Miscanthus adapted to the light environment by adjusting leaf morphological and biochemical properties independent of nitrogen treatments. GPP estimated using big leaf and multilayer models varied considerably, suggesting a multilayer model in which Vcmax changes both through time and canopy layer could be adopted into agricultural models to more accurately predict biomass production in biomass crop ecosystems.
Long‐lasting potentiation of hippocampal synaptic transmission by direct cortical input is mediated via endocannabinoids
Authors: Xu Jian‐Yi , Zhang Jian , Chen Chu
Published: March 2012

Key points 

Hippocampal CA1 pyramidal neurons receive dual sensory inputs from the cortex directly through the perforant path (PP) and indirectly through the Schaffer collaterals (SC).

Direct cortical inputs to CA1 pyramidal neurons through the PP are important for synaptic plasticity and memory formation.

In this study, we show that long‐lasting potentiation of glutamatergic synaptic transmission at SC synapses by pairing of PP–SC inputs was suppressed by pharmacological and genetic inhibition of CB1 receptors.

Inhibition of the enzyme synthesizing the endocannabinoid 2‐arachidonoylglycerol (2‐AG) prevented the pairing‐induced potentiation, while inhibition of the enzyme hydrolysing 2‐AG facilitated the potentiation.

Our results indicate that 2‐AG functions as a signalling mediator tuning synaptic efficacy at the proximal synapses of hippocampal CA1 pyramidal neurons while direct and indirect cortical inputs to the same neurons are spatiotemporally primed, suggesting that endocannabinoids are involved in the information processing and storage in the hippocampus.
The conductance of red blood cells from sickle cell patients: ion selectivity and inhibitors
Authors: Ma Y.‐L. , Rees D. C. , Gibson J. S. , Ellory J. C.
Published: March 2012

Key points 

The high cation permeability in red blood cells (RBCs) from patients with sickle cell disease (SCD) is central to pathogenesis and includes a deoxygenation‐induced pathway termed Psickle.

Here whole‐cell patch clamp configuration was used to record from RBCs of SCD patients and showed a conductance reversibly induced upon deoxygenation, permeable to univalent (Na+, K+, Rb+) and divalent (Ca2+, Mg2+) cations, and sensitive to tarantula spider toxin GsMTx‐4, Mn2+ and o‐vanillin.

Divalent cation permeability is particularly important as entry of Ca2+ stimulates the Gardos channel whilst Mg2+ loss will stimulate KCl cotransport.

In oxygenated RBCs, the conductance was pH sensitive, increasing as pH fell from 7.4 to 6, but unaffected when pH was raised from 7.4 to 8.

Results show a conductance that shares many features with the Psickle flux pathway, and indicating its possible identity as a stretch‐activated channel with activation requiring sickle cell haemoglobin (HbS) polymerisation.
Regulation of ventral surface CO2/H+‐sensitive neurons by purinergic signalling
Authors: Wenker Ian C. , Sobrinho Cleyton R. , Takakura Ana C. , Moreira Thiago S. , Mulkey Daniel K.
Published: March 2012

Key points 

The retrotrapezoid nucleus (RTN) is an important site of chemoreception, i.e. the mechanism by which the brain regulates breathing in response to changes in tissue CO2/H+.

Mechanisms underlying RTN chemoreception appear to involve direct CO2/H+‐mediated neuronal activation and indirect neuronal activation by CO2‐evoked ATP release (i.e. purinergic signalling) from astrocytes.

Here, we show in vitro and in vivo that purinergic signalling in the RTN contributes to ∼30% of RTN chemoreception.

Purinergic drive in the RTN involves gap junction hemichannels but not P2Y1 receptors.

These results clearly indicate that purinergic signalling contributes to integrated output of the RTN during hypercapnia and thus is an important determinant of respiratory drive.
Shape Optimization of a Self-deployable Anchor Designed for Percutaneous Mitral Valve Repair
Authors: Javid Farhad , Angeles Jorge , Pasini Damiano , Cecere Renzo
Published: March 2012

A new percutaneous annuloplasty technique for mitral regurgitation is proposed here. In this technique, inter-related anchors are first inserted around the annulus via a trans-septal catheter. The tethered wire passed through the anchors is then pulled to shrink the annulus and stop regurgitation. The anchors should withstand large deformation, applied during the delivery process, and should recover their original shape after being released inside the tissue. The shape of the anchors is, thus, optimized in an iterative process, to avoid stress concentration by minimizing the weighted rms value of the curvature along the anchor. The weight coefficients in each iteration are defined based on the stress distribution of the anchor obtained in the previous iteration. The procedure finally results in a structurally optimum anchor with a minimum in the maximum von Mises stress. This anchor is fabricated from Nitinol and tested in a cadaveric swine heart.
A Device to Control Implant and Bone-Cement Temperatures in Cemented Arthroplasty
Authors: Completo A. , Coutinho M. , Schiller M. , Ramos A. , Relvas C. , Simões J. A.
Published: March 2012

At present, most of the orthopaedic implants used in articular reconstruction are fixed to host bone using acrylic bone-cement. Bone-cement polymerization leads to an exothermic reaction with heat release and consequent temperature rise. The increase of temperature in the bone beyond the tolerated limits can develop osteocyte thermal necrosis and ultimately lead to bone resorption at the cement-bone interface, with subsequent loosening of the implant. Another issue that plays an important role in implant loosening is debonding of the cement from the implant initiated by crack formation at the interfacial voids. It is well established that low porosity enables better fatigue cement properties. Moderate preheating of the implant is expected to reverse the direction of polymerization, and has the ability to reduce interfacial void formation and improve interfacial shear strength. To increase the implant temperature at the initial cementing phase in order to reduce interfacial void formation, and subsequently, cool the implant in the latter cement polymerization phase to prevent the possibility of bone thermal necrosis, a new automated electronic device was designed to be use in cemented joint replacements. The developed device was specifically designed for the knee arthroplasty, namely for tibial-tray cementing. The device controls the heat flux direction between the tibial-tray and the atmosphere through the “Peltier effect,” using Peltier tablets. The device is placed on the tibial-tray during the cementing phase and starts to heat it in a first phase, promoting the polymerization that initiates at the warmer cement-implant interface. In a second phase, the heat flux in the Peltier tablets is inverted to extract the heat generated during cement polymerization. The device efficiency was evaluated by cementing several tibial-trays in bovine fresh bone and measuring the tray and cement temperatures. The temperature results in the implant and in the cement showed that the device increases and maintains the implant temperature above room temperature at the initial cementing phase, while in the subsequent phase it cools the tibial-tray and cement. Significant differences were found for peak cement temperatures between the tests performed with and without the device. The device showed its capacity to promote the beginning of cement polymerization at the implant interface contributing towards improving interfacial shear strength and in reducing the peak cement temperature in the subsequent polymerization process, thus contributing to the prevention of the bone thermal necrosis effect.
The Design and Initial Experimental Validation of an Active Myoelectric Transfemoral Prosthesis
Authors: Hoover Carl D. , Fulk George D. , Fite Kevin B.
Published: March 2012

This paper describes a single degree-of-freedom active-knee transfemoral prosthesis to be used as a test bed for the development of architectures for myoelectric control. The development of an active-knee transfemoral prosthesis is motivated by the inability of passive commercial prostheses to provide the joint power required at the knee for many activities of daily living such as reciprocal stair ascent, which requires knee power outputs of up to 4 W/kg. Study of myoelectric control based on surface electromyogram (EMG) measurements of muscles in the residual limb is motivated by the desire to restore direct volitional control of the knee using a minimally-invasive neuromuscular control interface. The presented work describes the design of a transfemoral prosthesis prototype including the structure, actuation, instrumentation, electronics, and real-time control architecture. The performance characteristics of the prototype are discussed in the context of the requisite knee energetics for a variety of common locomotive functions. This paper additionally describes the development of a single-subject diagnostic socket with wall-embedded surface EMG electrodes and the implementation of a control architecture for myoelectric modulation of knee impedance. Experimental results of level walking for a single subject with unilateral transfemoral amputation demonstrate the potential for direct EMG-based control of locomotive function.
Prosthetic Ankle-Foot System That Adapts to Sloped Surfaces
Authors: Nickel Eric A. , Hansen Andrew H. , Gard Steven A.
Published: March 2012

The anatomical ankle is capable of providing adaptation to sloped surfaces, a function that is not available in most traditional lower limb prostheses. Commercial prostheses that are claimed to adapt to slopes are limited by high cost, delay in response, reduced stability, and loss of energy through damping. The purpose of the present work was to develop a prototypical prosthetic ankle unit that adapts to sloped surfaces and is sufficiently durable for short-term take-home trials. The prototype switches between low and high rotational impedances by means of a wrap spring clutch mechanism. The clutch is held in a disengaged position when unloaded and deflection of a compressible pylon under axial load rotates a control collar and engages the clutch. The prototype was subjected to 100,000 cycles of mechanical endurance testing based on ISO 10328 standards to determine the suitability for two-week take-home testing. Three persons with unilateral transtibial amputations were recruited to test the prototype in the laboratory, providing subjective feedback through a survey and participating in a motion analysis study to confirm the performance of the slope adaptation function. Translation of the ankle moment-angle curves for all subjects along the ankle angle axis demonstrated a change of the ankle alignment when subjects walked with the adaptable ankle on surfaces of different slopes. The ankle moment-angle curves had a lower slope than the subjects’ usual prostheses, and some subjects had distinct flat regions in the moment-angle curves when using the adaptable ankle. The arbors of the clutch demonstrated significant wear when tested to 100,000 cycles based on ISO 10328 standards, yet the adaptable ankle continued to hold testing loads. The alignment change observed for sloped surfaces suggests the prototype was providing slope adaptation. The flat regions on the ankle moment-angle curves suggest the clutch may have been slipping. Refinement of the clutch engagement mechanism and continued development to reduce the weight and size of the prototype is needed prior to take-home testing.
Effects of insertion speed and trocar stiffness on the accuracy of needle position for brachytherapy
Authors: McGill Carl S. , Schwartz Jonathon A. , Moore Jason Z. , McLaughlin Patrick W. , Shih Albert J.
Published: March 2012

Purpose:

In prostate brachytherapy, accurate positioning of the needle tip to place radioactive seeds at its target site is critical for successful radiation treatment. During the procedure, needle deflection leads to seed misplacement and suboptimal radiation dose to cancerous cells. In practice, radiation oncologists commonly use high‐speed hand needle insertion to minimize displacement of the prostate as well as the needle deflection. Effects of speed during needle insertion and stiffness of trocar (a solid rod inside the hollow cannula) on needle deflection are studied.

Methods:

Needle insertion experiments into phantom were performed using a 22 factorial design (2 parameters at 2 levels), with each condition having replicates. Analysis of the deflection data included calculating the average, standard deviation, and analysis of variance (ANOVA) to find significant single and two‐way interaction factors.

Results:

The stiffer tungsten carbide trocar is effective in reducing the average and standard deviation of needle deflection. The fast insertion speed together with the stiffer trocar generated the smallest average and standard deviation for needle deflection for almost all cases.

Conclusions:

The combination of stiff tungsten carbide trocar and fast needle insertion speed are important to decreasing needle deflection. The knowledge gained from this study can be used to improve the accuracy of needle insertion during brachytherapy procedures.
Neurogenesis and Pattern Integration
Authors: Stern Peter R.
Published: March 2012

A specific set of functional properties can be attributed to immature granule cells developing in the hippocampus.
Kibra Is a Pez Dispenser
Authors: VanHook Annalisa M.
Published: March 2012

The FERM domain protein Pez is required for Hippo signaling to restrict stem cell proliferation in the fly gut.
Sphingolipids Lower the Death Threshold
Authors: Gough Nancy R.
Published: March 2012

Sphingolipids from other organellar membranes set the threshold for mitochondrial permeabilization leading to cell death.
Akting to Derepress Interferon Responses
Authors: Foley John F.
Published: March 2012

The kinase Akt1 specifically enhances type I interferon responses by relieving the repression of interferon-stimulated genes.
Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial
Authors: Jensen Jens-Ulrik Stæhr , Hein Lars , Lundgren Bettina , Bestle Morten Heiberg , Mohr Thomas , Andersen Mads Holmen , Thornberg Klaus Julius , Løken Jesper , Steensen Morten , Fox Zoë , Tousi Hamid , Søe-Jensen Peter , Lauritsen Anne Øberg , Strange Ditte Gry , Reiter Nanna , Thormar Katrin , Fjeldborg Paul Christian , Larsen Kim Michael , Drenck Niels-Erik , Johansen Maria Egede , Nielsen Lene Ryom , Østergaard Christian , Kjær Jesper , Grarup Jesper , Lundgren Jens D ,   The Procalcitonin And Survival Study (PASS) Group
Published: March 2012

Objectives

To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients.

Design

Secondary analysis from a randomised antibiotic strategy trial (the Procalcitonin And Survival Study). The randomised arms were conserved from the primary trial for the main analysis.

Setting

Nine mixed surgical/medical intensive care units across Denmark.

Participants

1200 adult intensive care patients, 18+ years, expected to stay +24 h. Exclusion criteria: bilirubin >40 mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling, pregnant/breast feeding and psychiatric patients.

Interventions

Patients were randomised to guideline-based therapy (‘standard-exposure’ arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements (‘high-exposure’ arm).

Main outcome measures

Primary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Secondary end points: (1) delta eGFR after starting/stopping a drug and (2) RIFLE criterionRisk‘R’,Injury‘I’ andFailure‘F’. Analysis was by intention to treat.

Results

28-day mortality was 31.8% and comparable (Jensenet al, Crit Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the high-exposure versus 3016/6949 (43.4%) in the ‘standard-exposure arm were spent with eGFR <60 ml/min/1.73 m2, p<0.001. In a multiple effects model, 3 piperacillin/tazobactam was identified as causing the lowest rate of renal recovery of all antibiotics used: 1.0 ml/min/1.73 m2/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m2/24 h) vs meropenem: 2.9 ml/min/1.73 m2/24 h (2.5 to 3.3 ml/min/1.73 m2/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m2/24 h (2.3 to 3.1 ml/min/1.73 m2/24 h)). eGFR <60 ml/min/1.73 m2in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively.

Conclusions

Piperacillin/tazobactam was identified as a cause of delayed renal recovery in critically ill patients. This nephrotoxicity was not observed when using other beta-lactam antibiotics.

Trial registration

ClinicalTrials.gov identifier:NCT00271752.
Quality assurance in the endoscopy unit: the view of endoscopy personnel
Authors: de Jonge V , Kuipers Ernst J , van Leerdam Monique E
Published: March 2012

Introduction

Quality of health services depend on the entire medical team. A supportive team culture and effective leadership is required for successful quality assurance (QA). The opinion of endoscopy personnel towards QA is unknown, while they have to collaborate in many quality projects.

Methods

A survey was sent to all endoscopy nurses, assistants and managers. It focused on the implementation of a QA programme. Further, a team assessment was included, focusing on leadership and team functioning, using scores on 5-point Likert scales, with 1 being a very positive opinion, and 5 being a very negative opinion towards the item.

Results

294 persons completed the questionnaire (44%). 87% expressed a positive attitude towards a QA programme, and 54% thought that the implementation of a nationwide QA programme for endoscopy would be feasible. Positive effects of QA were expected on publicity (62%) and overall quality (70%). Most important QA aspects were aftercare (97%) and patient experiences (96%). Concerns were raised about the time investment (18%) and disclosure of results towards media (24%). Team assessment showed good scores on `team working' with a mean score of 1.97. Lower scores were given to the `wider organization' (3.00) and `team process' (2.42).

Conclusion

Endoscopy personnel have a positive attitude towards a QA programme. Besides, the team culture and its leadership are ready for the implementation of a QA programme. Efforts should be made to improve team processes and the relation with the wider organisation to ensure an optimal team culture, aimed at quality improvement.
Teaching and learning on the ward round
Authors: Johnston Brian T , Valori Roland
Published: March 2012

Because of the European Working-Time Directive and ‘the New Deal’, there has been a significant reduction in opportunities for training. To address this deficit, consultants and junior doctors will need to alter their approach, making greater use of the learning opportunities that arise ‘on the job’. This paper provides some ideas on how to maximise learning without radically increasing workload. The paper first looks at attitudes and behaviours that influence the learning environment. If the senior doctor encourages discussion and shows enthusiasm during clinical duties, junior doctors will learn more. Second, the paper focuses on key skills that can be adopted to ensure appropriate learning. These attitudes, behaviours and skills can help consultants and senior doctors improve the effectiveness of their teaching in an era when the time available for junior doctors to learn has been reduced.
Improving outpatient services: the Southampton IBD virtual clinic
Authors: Hunter Jo , Claridge Andrew , James Shirley , Chan David , Stacey Bernard , Stroud Mike , Patel Praful , Fine David , Cummings J R Fraser
Published: March 2012

The follow-up of inflammatory bowel disease (IBD) patients is challenging due to the relapsing remitting nature of the diseases, the wide spectrum of severity and complexity as well as the need for monitoring of long-term complications and drug treatments. Conventional outpatient follow-up lacks flexibility for patients and there are competing pressures for clinic time. Alternative follow-up pathways include telephone clinics, self-management programmes or discharging patients. The IBD virtual clinic (VC) is a further option. Patients with an established diagnosis for >2 years, who have been stable for >1 year, do not have primary sclerosing cholangitis and who give their consent, are entered into the VC system. Two months before their annual follow-up is due patients are sent blood test forms and a simple questionnaire with an information sheet. If they meet any of the criteria on the questionnaire, they are asked to contact the IBD specialist nursing team to discuss their situation. The blood test results and the patient's database entry are reviewed to ensure that they are not due surveillance investigations. The patients and their GPs then receive a letter informing them of their management plan. We currently follow-up 20% of the Southampton IBD cohort using the VC. The VC system is an innovative, efficient and patient-responsive method for following up mild to moderate IBD. It is well liked by patients but is dependent on a well-maintained database with good integration of IT systems and requires both clerical and IBD nurse specialist support.
Genetic testing for coat colour in cats
Authors: Wensley Sean
Published: March 2012

You recently attended a cat show where a company was offering genetic testing for coat colour in cats. The test is performed on cells collected using a mouth swab. Is this an ethically acceptable scientific advancement?
Gastrointestinal disease in rabbits 2. Intestinal diseases
Authors: Lord Brigitte
Published: March 2012

Intestinal diseases in rabbits can develop as a result of many causes. Dietrelated problems are a common aetiology of intestinal disorders but infectious (bacterial, viral, parasitic), idiopathic and neoplastic diseases are also seen with relative frequency. This article describes the diagnosis and approach to treatment of intestinal diseases in rabbits. An article in the February issue of In Practice (volume 34, pages90–96) considered gastric diseases in this species.
Metaplastic breast cancer: clinicopathological features and its prognosis
Authors: Lee Hyewon , Jung So-Youn , Ro Jae Yun , Kwon Youngmee , Sohn Joo Hyuk , Park In Hae , Lee Keun Seok , Lee Seeyoun , Kim Seok Won , Kang Han Sung , Ko Kyoung Lan , Ro Jungsil
Published: March 2012

Aims

The prognosis of metaplastic breast cancer (MBC) is reportedly worse than that of triple-negative invasive ductal carcinoma (TN-IDC), but the determinants of poor prognosis are not yet known.

Methods

Patients from two Korean cancer centres were included in this study (67 MBC and 520 TN-IDC). Characteristics of the two disease groups, including clinical parameters, histological features, chemoresponsiveness, disease recurrence and survival estimates, were evaluated.

Results

MBC presented with larger tumours, more frequent distant metastasis and higher histological grade compared with TN-IDC (p<0.001). All but nine patients with MBC had triple-negative disease. Disease-free survival and overall survival (OS) of MBC were worse than TN-IDC (p<0.001). Multivariable analysis of disease-free survival revealed MBC type as an independent prognostic factor (HR 2.53; 95% CI 1.32 to 4.84) along with lymph node metastasis and implementation of breast conserving surgery. For OS, MBC type remained a significant prognostic factor (HR 2.56; 95% CI 1.18 to 5.54). Chemoresponsiveness of MBC and TN-IDC were similar in both neoadjuvant (p=1.000) and advanced disease settings (p=0.508). For a given MBC type, risk factors for disease recurrence included the presence of a squamous component (HR 4.0; 95% CI 1.46 to 10.99) and lymph node metastasis (HR 4.76; 95% CI 1.67 to 13.60); the risk factor for OS was initial distant metastasis (HR 10.77; 95% CI 2.59 to 44.76).

Conclusions

MBC had worse survival outcomes compared with TN-IDC. Poor prognosis for MBC was likely caused by frequent recurrence with high initial stage and the unique biology of MBC itself.