bluuebunny/crossref_metadata_2025 huggingface dataset:
Photostability and Skin Penetration of Different E‐Resveratrol‐Loaded Supramolecular Structures
Authors: Detoni Cassia Britto , Souto Gabriele Dadalt , da Silva Ana Luiza Maurer , Pohlmann Adriana Raffin , Guterres Silvia Stanisuaski
Published: March 2012

It is desirable and challenging to prevent E‐resveratrol (E‐RSV) from photoisomerizing to its Z‐configuration to preserve its biological and pharmacological activities. The aim of this research was to evaluate the photostability of E‐RSV‐loaded supramolecular structures and the skin penetration profile of chemically and physically stable nanoestructured formulations. Different supramolecular structures were developed to act as carriers for E‐RSV, that is, liposomes, polymeric lipid‐core nanocapsules and nanospheres and solid lipid nanoparticles. The degrees of photostability of these formulations were compared with that of an ethanolic solution of E‐RSV. The skin penetration profiles of the stable formulations were obtained using vertical diffusion cells (protected from light and under UVA radiation) with porcine skin as the membrane, followed by tape stripping and separation of the viable epidermis and dermis in a heated water bath. Photoisomerization was significantly delayed by the association of resveratrol with the nanocarriers independently of the supramolecular structure. Liposomes were the particles capable of maintaining E‐RSV concentration for the longest time. On the other hand, E‐RSV‐loaded liposomes reduced in size showing low physical stability under UVA radiation. In the dark, the skin penetration profiles were very similar, but under UVA radiation the E‐RSV‐loaded nanocarriers showed increasing amounts in the total epidermis.
Strong divergences in regional distributions in Romania: recent ecological constraints in dragonflies (Odonata) versus ancient biogeographical patterns in butterflies (Lepidoptera: Rhopolocera)
Authors: RÁKOSY LÁSZLÓ , HEISER MARKUS , MANCI COSMIN‐OVIDIU , SCHMITT THOMAS
Published: March 2012

Abstract.  1. While the biogeographical structuring of Europe as a whole is already relatively well understood, patterns at the more regional scale are still poorly explored. Especially the influence of differing ecological demands among species groups on regional distribution patterns is mostly unresolved. Therefore, we compare the distributions of strictly terrestrial butterflies with those of semi‐aquatic dragonflies.

2. We analysed a regionalised distribution of the 196 butterfly and 68 dragonfly taxa of Romania with cluster analyses and principal component analyses, and worked out the different faunal regions and faunal elements for this country.

3. We obtained a clear regional structuring for the butterflies (e.g. Transylvanian Basin, Carpathians, SE Romania, W/SW Romania), but only a vertical structuring in the dragonflies from the Danube lowlands to the elevations of the Carpathians.

4. This structure implies a recent distribution trigger based on ecological and climatic constraints in dragonflies with water and energy availability being of high importance.

5. The more ancient biogeographical pattern in butterflies reflects the different biogeographical elements of Europe and the connections of the Carpathian regions to the Balkan Peninsula and the Eastern European steppes, with energy being of considerably higher importance for butterfly occurrences than water availability.
Antimitochondrial antibody ‐M2 positive autoimmune hepatitis during standard of care for chronic hepatitis C
Authors: Macaluso Fabio Salvatore , Alessi Nicola , Cabibi Daniela
Published: March 2012

The current standard of care (SoC) for chronic hepatitis C, i.e. the combination of a pegylated‐interferon (PEG‐IFN) with ribavirin (RBV), may activate underlying autoimmune conditions. Particularly, interferon (IFN) has been known to induce or exacerbate autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in hepatitis C virus patients. We describe a severe, acute‐onset antimitochondrial antibody (AMA)‐M2 positive AIH appearing during the last weeks of SoC in a woman with chronic hepatitis C and no previous history of autoimmunity, and resolving on protracted steroids. In this context, the relevance of the characterization of the immunoglobulin isotype of portal plasma cells for a more appropriate diagnosis of autoimmune liver diseases can be emphasized.
Association of Adrenocorticotrophin and Cortisol Concentrations with Peripheral Blood Leukocyte Cytokine Gene Expression in Septic and Nonseptic Neonatal Foals
Authors: Gold J.R. , Cohen N.D. , Welsh T.H.
Published: March 2012

Background

The hypothalamic‐pituitary‐adrenal (HPA) is influenced by the proinflammatory cytokinesIL‐6,IL‐1β, andTNF‐α in critically ill humans. Information about the association of cytokines with theHPAaxis in neonatal foals is lacking.

Hypothesis/Objectives

The objectives were to describe for hospitalized septic and nonseptic foals (1) temporal changes in blood concentrations ofACTH, and cortisol, and leukocyte cytokine gene expression, and (2) coassociation of theseHPAaxis hormones with blood leukocyte cytokine gene expression.

Animals

Hospitalized septic foals (N = 15) and hospitalized nonseptic foals (N = 11).

Methods

Blood samples, obtained from study foals at admission (T = 0), and 24 (T = 1), 48 (T = 2), 72 (T = 3), and 96 (T = 4) hours after admission, were processed to isolate RNA from leukocytes and to harvest plasma and serum for hormone assays. Plasma ACTH and serum cortisol concentrations were determined by radioimmunoassay. LeukocytemRNAexpression of IL‐1β IL‐6, IL‐8, IL‐10, and TNF‐α was determined using RT‐PCR.

Results

Cortisol concentrations were greater (P < .05) in foals at admission than at other time points. The expressions of IL‐8 and IL‐10mRNAwere lower (P < .05) at each time point in septic than in nonseptic foals. Among septic foals, ACTH was positively associated (P = .0026) with IL‐6mRNAexpression.

Conclusions

Sepsis influences secretion of theHPAaxis hormones and expression of cytokines in foals. A positive association with theHPAaxis andIL‐6 expression was detected. The clinical importance of these findings requires additional study.
Modeling Validation and Simulation of an Anode Supported SOFC Including Mass and Heat Transport, Fluid Flow and Chemical Reactions
Authors: Andersson Martin , Yuan Jinliang , Sunde´n Bengt , Li Ting Shuai , Wang Wei Guo
Published: March 2012

Fuel cells are electrochemical devices that directly transform chemical energy into electricity, which are promising for future energy systems, since they are energy efficient and, when hydrogen is used as fuel, there are no direct emissions of greenhouse gases. The cell performance depends strongly on the material characteristics, the operating conditions and the chemical reactions that occur inside the cell. The chemical- and electrochemical reaction rates depend on temperature, material structure, catalytic activity, degradation and the partial pressures for the different species components. There is a lack of information, within the open literature, concerning the fundamentals behind these reactions. Experimental as well as modeling studies are needed to reduce this gap. In this study experimental data collected from an intermediate temperature standard SOFC with H2/H2O in the fuel stream are used to validate a previously developed computational fluid dynamics model based on the finite element method. The developed model is based on the governing equations of heat and mass transport and fluid flow, which are solved together with kinetic expressions for internal reforming reactions of hydrocarbon fuels and electrochemistry. This model is further updated to describe the experimental environment concerning cell design. Discussion on available active area for electrochemical reactions and average ionic transport distance from the anodic- to the cathodic three-phase boundary (TPB) are presented. The fuel inlet mole fractions are changed for the validated model to simulate a H2/H2O mixture and 30% pre-reformed natural gas.
Current Mode Control of Fuel Cell Fed Interleaved Boost Converter for Ripple Current Minimization
Authors: Latha K. , Maadhuri M. , Maheswari B. Uma , Rajalakshmi N. , Dhathathreyan K. S.
Published: March 2012

Fuel cells normally supply high current at low voltage. Hence they need to be integrated with boost converters to supply load at elevated voltages. Boosting of voltage at the load level amplifies the effect of ripple in load current at the input side. The life time of fuel cell catalyst reduces with the increase in current ripple. This paper proposes an effective solution to reduce the ripple with the use of interleaved boost converters and non-linear carrier based current mode control. Performance of the controller has been tested in simulation and validated through experimentation on a 1.2kW fuel cell stack for wide variations in load and fuel flow conditions. It is observed that, compared to other control techniques, the proposed controller has better dynamic response and it does not need any complex multiplier or divider circuit for its implementation. A prototype rated 1.2 KW has been built and tested.
Compression Modeling and Transport Characterization of the PEM Fuel Cell Diffusion Medium
Authors: Schulz Volker P. , Mukherjee Partha P. , Andra¨ Heiko
Published: March 2012

Despite tremendous progress in recent years, a pivotal performance limitation in PEM fuel cells manifests in terms of mass transport loss owing to liquid water transport and resulting flooding. A key contributor to the mass transport loss is the cathode gas diffusion layer (GDL) due to the blockage of available pore space by liquid water thus rendering hindered oxygen transport to the active reaction sites in the electrode. The GDL, typically a non-woven carbon paper or woven carbon cloth, thus plays an important role in the overall water management in PEM fuel cells. The underlying pore-morphology and the pore wetting characteristics have significant influence on the flooding dynamics in the GDL. Another important factor is the role of cell compression on the GDL microstructural change. In this work, we investigate the influence of GDL microstructure change under compression on the transport behavior. We will present an improved compression model based on the micro finite element approach. The compression of reconstructed GDL microstructures along with effective property estimation and transport characterization are elucidated.
PEM Fuel Cell Gas Diffusion Layer Modelling of Pore Structure and Predicted Liquid Water Saturation
Authors: Hinebaugh J. , Bazylak A.
Published: March 2012

An unstructured, three-dimensional pore network model is employed to describe the effect of through-plane porosity profiles on liquid water saturation within the gas diffusion layer (GDL) of the polymer electrolyte membrane fuel cell. Random fibre placements are based on the porosity profiles of six commercially available GDL materials recently obtained through x-ray computed tomography experiments. The pore space is characterized with a maximal ball algorithm, and invasion percolation-based simulations are performed. It is shown that water tends to accumulate in regions of relatively high porosity due to the lower associated capillary pressures. It is predicted that GDLs tailored to have smooth porosity profiles will have fewer pockets of high saturation levels within the bulk of the material. The results provide a more detailed picture of the possible water distributions in GDLs during operation.
Prediction the Differences of Permeability Between Carbon Fiber Paper and Carbon Fiber Cloth in PEM Fuel Cells
Authors: Gao Yuan
Published: March 2012

This study is using the multiple relaxation time Lattice Boltzmann method to calculate the permeability of carbon fiber paper and carbon fiber cloth gas diffusion layers (GDL). The 3D gas diffusion layers are generated by X-ray computed tomography, This method involve generation of 3D digital model of gas diffusion layers acquired through X-ray micro-tomography at resolution of a few micros. The reconstructed 3D images were then read into the LBM model to calculate the anisotropic permeability of carbon fiber paper and carbon fiber cloth GDL. We investigated the relationships between the anisotropic permeability and porosity and compare the difference between the two different kinds of GDLs when they have the similar porosity. We also calculate the permeability with different viscosity and compare the two results from the carbon fiber paper and carbon fiber cloth. It is useful for selection of materials for high performance gas diffusion media and can improve the performance of the fuel cells.
PH3 Effects on the Electrochemical Degradation of SOFC Anode
Authors: Guo Huang , Iqbal Gulfam , Kang Bruce S.
Published: March 2012

Solid Oxide Fuel Cell anode is readily degraded by trace amount of Phosphine (PH3) contaminant that is found in coal-derived syngas. PH3 interacts with the anode material and affects its electrochemical performance by forming secondary phases. In this paper, the influence of the ppm level of PH3 with moisture is investigated on the formation of secondary phases and hence on anode electrochemical performance degradation. Nickel yttria-stabilized zirconia (Ni-YSZ) anode shows immediate and severe electrochemical degradation due to PH3 in moist hydrogen condition attributed to the nickel-phosphate secondary phase formation. Whereas in dry hydrogen condition, nickel-phosphide is preferred to form on the anode surface that shows less deleterious effects on SOFC performance as compared to nickel-phosphate.
Resource Letter EIRLD-2: Effects of Ionizing Radiation at Low Doses
Authors: Wilson Richard
Published: March 2012

This Resource Letter provides a guide to the literature on the effects of ionizing radiation on people at low doses. Journal articles, books and web pages are provided for the following: data at high dose levels, effects of moderate to high doses (leukemia, solid cancer, lung cancer, childhood cancer, and non-cancer outcomes), effects of dose rate, relationship to background, supra linearity and hormesis, and policy implications.
Apparent Loss of Vibrio vulnificus from North Carolina Oysters Coincides with a Drought-Induced Increase in Salinity
Authors: Froelich Brett A. , Williams Tiffany C. , Noble Rachel T. , Oliver James D.
Published: March 2012

Despite years of successful isolation of
Vibrio vulnificus
from estuarine waters, beginning in 2007, it was extremely difficult to culture
V. vulnificus
from either North Carolina estuarine water or oyster samples. After employing culture-based methods as well as PCR and quantitative PCR for the detection of
V. vulnificus
, always with negative results, we concluded that this pathogen had become nearly undetectable in the North Carolina estuarine ecosystem. We ensured that the techniques were sound by seeding North Carolina oysters with
V. vulnificus
and performing the same tests as those previously conducted on unadulterated oysters.
V. vulnificus
was readily detected in the seeded oysters using both classes of methods. Furthermore, oysters were obtained from the Gulf of Mexico, and
V. vulnificus
was easily isolated, confirming that the methodology was sound but that the oysters and waters of North Carolina were lacking the
V. vulnificus
population studied for decades. Strikingly, the apparent loss of detectable
V. vulnificus
coincided with the most severe drought in the history of North Carolina. The drought continued until the end of 2009, with an elevated water column salinity being observed throughout this period and with
V. vulnificus
being nearly nonexistent. When salinities returned to normal after the drought abated in 2010, we were again able to routinely isolate
V. vulnificus
from the water column, although we were still unable to culture it from oysters. We suggest that the oysters were colonized with a more salt-tolerant bacterium during the drought, which displaced
V. vulnificus
and may be preventing recolonization.
Secretory Pathway-Dependent Localization of the Saccharomyces cerevisiae Rho GTPase-Activating Protein Rgd1p at Growth Sites
Authors: Lefèbvre Fabien , Prouzet-Mauléon Valérie , Hugues Michel , Crouzet Marc , Vieillemard Aurélie , McCusker Derek , Thoraval Didier , Doignon François
Published: March 2012

Establishment and maintenance of cell polarity in eukaryotes depends upon the regulation of Rho GTPases. In
Saccharomyces cerevisiae
, the Rho GTPase activating protein (RhoGAP) Rgd1p stimulates the GTPase activities of Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively. Consistent with the distribution of Rho3p and Rho4p, Rgd1p is found mostly in areas of polarized growth during cell cycle progression. Rgd1p was mislocalized in mutants specifically altered for Golgi apparatus-based phosphatidylinositol 4-P [PtdIns(4)P] synthesis and for PtdIns(4,5)P
2
production at the plasma membrane. Analysis of Rgd1p distribution in different membrane-trafficking mutants suggested that Rgd1p was delivered to growth sites via the secretory pathway. Rgd1p may associate with post-Golgi vesicles by binding to PtdIns(4)P and then be transported by secretory vesicles to the plasma membrane. In agreement, we show that Rgd1p coimmunoprecipitated and localized with markers specific to secretory vesicles and cofractionated with a plasma membrane marker. Moreover,
in vivo
imaging revealed that Rgd1p was transported in an anterograde manner from the mother cell to the daughter cell in a vectoral manner. Our data indicate that secretory vesicles are involved in the delivery of RhoGAP Rgd1p to the bud tip and bud neck.
Self-reported violations during medication administration in two paediatric hospitals
Authors: Alper Samuel J , Holden Richard J , Scanlon Matthew C , Patel Neal , Kaushal Rainu , Skibinski Kathleen , Brown Roger L , Karsh Ben-Tzion
Published: March 2012

Content

Violations of safety protocols are paths to adverse outcomes that have been poorly addressed by existing safety efforts. This study reports on nurses' self-reported violations in the medication administration process.

Objective

To assess the extent of violations in the medication administration process among nurses.

Design, setting and participants

Participants were 199 nurses from two US urban, academic, tertiary care, free-standing paediatric hospitals who worked in a paediatric intensive care unit (PICU), a haematology-oncology-transplant (HOT) unit or a medical-surgical (Med/Surg) unit. In a cross-sectional survey, nurses were asked about violations in routine or emergency situations in three steps of the medication administration process.

Main outcome measure

Self-reported violations of three medication administration protocols were made using a seven-point 0–6 scale from ‘not at all’ to ‘a great deal’.

Results

Analysis of variance identified that violation reports were highest for emergency situations, rather than for routine operations, highest by HOT unit nurses, followed by PICU nurses and then Med/Surg unit nurses, and highest during patient identification checking, followed by matching a medication to a medication administration record, and then documenting an administration. There was also a significant three-way interaction among violation situation, step in the process, and unit.

Conclusions

Protocol violations occur throughout the medication administration process and their prevalence varies as a function of hospital unit, step in the process, and violation situation. Further research is required to determine whether these violations improve or worsen safety, and for those that worsen safety, how to redesign the system of administration to reduce the need to violate protocol to accomplish job tasks.
Transfusion-associated necrotising enterocolitis in neonates
Authors: Stritzke Amelie I , Smyth John , Synnes Anne , Lee Shoo K , Shah Prakesh S
Published: March 2012

Objective

To evaluate the association between blood transfusion in previous 2 days and necrotising enterocolitis (NEC) in infants admitted to neonatal intensive care units in Canada.

Patients and Methods

Using the Canadian Neonatal Network database of admissions to neonatal intensive care units from 2003 to 2008, cases with NEC were matched with controls by gestational age (GA) at birth. Exposure to transfusion within 2 days of NEC (for cases) or 2 days before the median age of NEC diagnosis among cases of the same GA (for controls) was determined. After controlling for confounders, the differences in characteristics and neonatal outcomes of transfusion-associated NEC (TANEC) and NEC not associated with transfusion (non-TANEC) were compared.

Results

NEC cases (n=927) were matched with 2781 controls. Transfusion in previous 2 days was significantly higher in NEC cases than in controls (15.5 vs 7.7%; adjusted OR (AOR) 2. 44; 95% CI 1.87 to 3.18). TANEC cases versus non-TANEC cases had a lower mean GA (25.8 vs 29.3 weeks), a lower mean birthweight (885 vs 1373 grams), and a higher proportion of infants with SNAPII score >20 (52.1 vs 22.9%). After adjustment for confounders, no significant differences in mortality (AOR 1.28, 95% CI 0.82 to 2.01), severe retinopathy (AOR 1.15, 95% CI 0.71 to 1.87), or severe neurological injury (AOR 0.83, 95% CI 0.43 to 1.60) were identified.

Conclusions

Exposure to transfusion in previous 2 days was an independent risk factor for NEC. After controlling for confounders, no significant differences in mortality and morbidities were observed between infants who had transfusion-associated NEC and those with NEC not associated with transfusion.
Prognostic value of nuclear factor κ B expression in patients with advanced cervical cancer undergoing radiation therapy followed by hysterectomy
Authors: Baiocchi Glauco , Begnami Maria Dirlei , Fukazawa Elza Mieko , Oliveira Renato Almeida Rosa , Faloppa Carlos Chaves , Kumagai Lillian Yuri , Badiglian-Filho Levon , Pellizzon Antonio Cassio Assis , Maia Maria Aparecida Conte , Jacinto Alexandre Arthur , Soares Fernando Augusto , Lopes Ademar
Published: March 2012

Aims

The nuclear factor κ B (NF-κB) family comprises transcription factors that promote the development and progression of cancer. The NF-κB pathway is induced by radiation therapy and may be related to tumour radioresistance. The aim of this study was to evaluate the expression of NF-κB as a predictor of the response to radiotherapy and its value as a prognostic marker.

Methods

A retrospective analysis was performed in a series of 32 individuals with stage IB2 and IIB cervical cancer who underwent radiotherapy, followed by radical hysterectomy, from January 1992 to June 2001. NF-κB-p65 and NF-κB-p50 expression was examined by immunohistochemistry in biopsies from all patients before radiotherapy and in 12 patients with residual tumours after radiotherapy.

Results

16 (50%) patients had residual disease after radical hysterectomy. The median follow-up time was 73.5 months, and the 5-year overall survival was 66.5%. Before radiotherapy, cytoplasmic expression of NF-κB-p65 and NF-κB-p50 was noted in 91% and 97% of cases, respectively, versus 59% of cases with nuclear expression of these subunits. Cytoplasmic expression of NF-κB-p65 and NF-κB-p50 in the residual tumours after radiotherapy was observed in 50% of cases; 75% of cases with residual tumours had nuclear expression of NF-κB-p50 versus none with NF-κB-p65. NF-κB-p65 and NF-κB-p50 did not correlate with the risk of residual tumours after radiotherapy or recurrence or death.

Conclusions

These data suggest that NF-κB does not predict the response to radiotherapy and does not correlate with poor outcomes in advanced cervical cancer.
Trainers' perceptions of the direct observation of practical skills assessment in histopathology training: a qualitative pilot study
Authors: Finall Alison
Published: March 2012

Aims

This pilot study of the direct observation of practical skills (DOPS) assessment of histopathology trainees is needed in the absence of existing information on histopathology in the UK. The aim of the study was to explore the experiences and perceptions of trainers in using the DOPS tool with histopathology trainees.

Methods

A qualitative approach was taken using paper-based questionnaires to consultants in a single teaching hospital histopathology department.

Results

DOPS was perceived by all trainers as a valid form of assessment. There was a spread of opinion regarding its feasibility, with some respondents raising concern about its impact on time. 28% of respondents were doubtful about the formative nature of DOPS. All stated the assessment was fair.

Conclusions

Themes that have emerged include concerns about impact on trainer time, whether DOPS is used in a formative manner and concerns about the amount of guidance provided to trainers. Further research is required to expand on these points.
Utility of multispectral imaging in automated quantitative scoring of immunohistochemistry
Authors: Fiore Christopher , Bailey Dyane , Conlon Niamh , Wu Xiaoqiu , Martin Neil , Fiorentino Michelangelo , Finn Stephen , Fall Katja , Andersson Swen-Olof , Andren Ove , Loda Massimo , Flavin Richard
Published: March 2012

Background

Automated scanning devices and image analysis software provide a means to overcome the limitations of manual semiquantitative scoring of immunohistochemistry. Common drawbacks to automated imaging systems include an inability to classify tissue type and an inability to segregate cytoplasmic and nuclear staining.

Methods

Immunohistochemistry for the membranous marker α-catenin, the cytoplasmic marker stathmin and the nuclear marker Ki-67 was performed on tissue microarrays (TMA) of archival formalin-fixed paraffin-embedded tissue comprising 471 (α-catenin and stathmin) and 511 (Ki-67) cases of prostate adenocarcinoma. These TMA were quantitatively analysed using two commercially available automated image analysers, the Ariol SL-50 system and the Nuance system from CRi. Both systems use brightfield microscopy for automated, unbiased and standardised quantification of immunohistochemistry, while the Nuance system has spectral deconvolution capabilities.

Results

Overall concordance between scores from both systems was excellent (r=0.90; 0.83–0.95). The software associated with the multispectral imager allowed accurate automated classification of tissue type into epithelial glandular structures and stroma, and a single-step segmentation of staining into cytoplasmic or nuclear compartments allowing independent evaluation of these areas. The Nuance system, however, was not able to distinguish reliably between tumour and non-tumour tissue. In addition, variance in the labour and time required for analysis between the two systems was also noted.

Conclusion

Despite limitations, this study suggests some beneficial role for the use of a multispectral imaging system in automated analysis of immunohistochemistry.
Cardiac response to doxorubicin and dexrazoxane in intact and ovariectomized young female rats at rest and after swim training
Authors: Calvé Annie , Haddad Rami , Barama Sarah-Neiel , Meilleur Melissa , Sebag Igal A. , Chalifour Lorraine E.
Published: March 2012

The impact of cancer therapies on adult cardiac function is becoming a concern as more children survive their initial cancer. Cardiovascular disease is now a significant problem to adult survivors of childhood cancer. Specifically, doxorubicin (DOX) may be particularly harmful in young girls. The objective of this study was to characterize DOX damage and determine the ability of dexrazoxane (DEX) to reduce DOX-mediated cardiac damage in sedentary and swim-trained female rats. Female Sprague-Dawley rats were left intact or ovariectomized (OVX) at weaning then injected with DEX (60 mg/kg) before DOX (3 mg/kg), DOX alone, or PBS. Rats were separated into sedentary and swim cohorts. Body weight was reduced in DOX:DEX- but not PBS- or DOX-treated rats. Echocardiographic parameters were similar in sedentary rats. Swim training revealed greater concentric remodeling in DOX-treated rats and reduced fractional shortening in DOX:DEX-treated rats. Calsequestrin 2 was reduced with DOX and increased with DOX:DEX postswim. Sarco(endo)plasmic reticulum Ca2+-ATPase 2a was reduced and calsequestrin 2 reduced further by swim training only in intact rats. OVX rats were heavier and developed eccentric remodeling post-swim with DOX and eccentric hypertrophy with DOX:DEX. Changes in SERCA2a and calsequestrin 2 expression were not observed. Ovariectomized DOX- and DOX:DEX-treated rats stopped growing during swim training. DEX coinjection did not relieve DOX-mediated cardiotoxicity in intact or hormone-deficient rats. DOX-mediated reductions in growth, cardiac function, and expression of calcium homeostasis proteins were exacerbated by swim. DEX coadministration did not substantially relieve DOX-mediated cardiotoxicity in young female rats. Ovarian hormones reduce DOX-induced cardiotoxicity.
Calcific Tendonitis of the Rotator Cuff: An Unusual Case
Authors: Mitsui Yasuhiro , Gotoh Masafumi , Tanesue Ryo , Shirachi Isao , Shibata Hideaki , Nakama Kenjiro , Okawa Takahiro , Higuchi Fujio , Nagata Kensei
Published: March 2012

Few case reports have described the surgical treatment of calcifying tendonitis of the subscapularis tendon. We present a case of symptomatic diffuse calcifying tendonitis involving the subscapularis and infraspinatus insertions that was difficult to detect arthroscopically. The patient was treated with arthroscopic incision of the tendinous insertions thorough removal of the calcific deposits and subsequent repair using a suture-anchor technique. Two years after the surgical procedure, the patient was completely pain-free and attained full range of motion. Radiographic evaluation performed 2 years after the procedure revealed no calcific deposits. We conclude that the combination of incision of the subscapularis and infraspinatus insertions, complete removal of the calcific deposits, and subsequent suture-anchor repair in an all-arthroscopic manner can lead to an excellent clinical outcome without compromising the functional integrity of the rotator cuff tendons.
Mechanisms of Ploidy Increase in Human Cancers: A New Role for Cell Cannibalism
Authors: Krajcovic Matej , Overholtzer Michael
Published: March 2012

Aneuploidy is a hallmark of human cancers originating from abnormal mitoses. Many aneuploid cancer cells also have greater-than-diploid DNA content, suggesting that polyploidy is a common precursor to aneuploidy during tumor progression. Polyploid cells can originate from cell fusion, endoreplication, and cytokinesis failure. Recently we found that cell cannibalism by entosis, a form of cell engulfment involving live cells, also leads to polyploidy, as internalized cells disrupt cytokinesis of their engulfing cell hosts. By this mechanism, cannibalistic cell behavior could promote tumor progression by leading to aneuploidy. Here, we discuss cell cannibalism in cancer and other mechanisms that result in the formation of polyploid cancer cells. Cancer Res; 72(7); 1596–601. ©2012 AACR.
Food Hypersensitivity and Otolaryngologic Conditions in Young Children
Authors: Paddack Angela , Gibbons Troy , Smith Chandra , Patil Sowmya , Richter Gresham T.
Published: March 2012

Objectives/Hypothesis

To explore the relationship between food hypersensitivity and common upper aerodigestive disorders found in children younger than 2 years.

Study Design

Case control study.

Setting

Tertiary pediatric gastroenterology/otolaryngology clinics.

Methods

Two‐year retrospective chart review of a common cohort of children younger than 2 years with suspected cow’s milk protein allergy (CMPA). Patients were managed in both a tertiary pediatric gastroenterology and otolaryngology clinic and compared with a control study group.

Results

One hundred ninety‐one children with CMPA were reviewed. One hundred forty‐one had aerodigestive complaints, with 101 having sufficient follow‐up to participate in the study. Ninety‐one percent of this final patient group demonstrated improved symptoms following dairy elimination. Twenty‐five patients (27%) had associated otolaryngologic (ear, nose, and throat [ENT]) issues that had been refractory to maximal gastroesophageal reflux therapy. The most common associated upper aerodigestive conditions were persistent upper airway congestion (72%) and oropharyngeal dysphagia (80%). Sixty percent of ENT disease improved with elimination diet. Eosinophilic esophagitis was noted in 36% of the cohort who had mucosal biopsies performed. Otolaryngology intervention was much more common in the cohort of children with CMPA compared with controls (odds ratio, 33.78; 95% confidence interval, 7.55, 151.03).

Conclusions

CMPA is difficult to diagnose because of limited accurate diagnostic tools, especially in young children. This study suggests a relationship between CMPA and otolaryngologic conditions in children younger than 2 years. Some patients in this study showed symptom improvement via an elimination diet. Early recognition of otolaryngologic manifestations of CMPA may help manage this condition in young children.
Sialocele after Parotid Surgery
Authors: Herbert Hayley A. , Morton Randall P.
Published: March 2012

Objective

To assess possible factors contributing to the occurrence of a sialocele after parotid surgery.

Study Design

Case series with chart review.

Setting

Secondary otolaryngology service.

Methods

One hundred two consecutive parotid operations by 1 surgeon were recorded. A high rate of sialocele formation was addressed by identifying possible contributing factors, sequentially introducing changes, and then analyzing the effect of such changes.

Results

Twenty patients developed a sialocele (19.6%). Demographic variables of those who developed a sialocele were similar to those who did not. Factors examined included partial versus complete superficial parotidectomy, use of Surgicel, vacuum drain pressure, and postoperative duration for surgical drain. The only significant factor on regression analysis for increasing the risk of a sialocele development was the use of Surgicel (P =. 023). Once the use of Surgicel stopped, the rate of sialocele formation diminished markedly (from 28.6% to 11.3%).

Conclusions

Sialocele can cause significant problems for the patient and surgeon in terms of delayed wound healing and increased clinic resources and frustration. This study suggests that the use of products such as Surgicel increases the risk of postoperative sialocele formation.
Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth
Authors: Abéngozar María Angeles , de Frutos Sergio , Ferreiro Sergio , Soriano Joaquím , Perez-Martinez Manuel , Olmeda David , Marenchino Marco , Cañamero Marta , Ortega Sagrario , Megias Diego , Rodriguez Antonio , Martínez-Torrecuadrada Jorge L.
Published: March 2012

Membrane-anchored ephrinB2 and its receptor EphB4 are involved in the formation of blood and lymphatic vessels in normal and pathologic conditions. Eph/ephrin activation requires cell-cell interactions and leads to bidirectional signaling pathways in both ligand- and receptor-expressing cells. To investigate the functional consequences of blocking ephrinB2 activity, 2 highly specific human single-chain Fv (scFv) Ab fragments against ephrinB2 were generated and characterized. Both Ab fragments suppressed endothelial cell migration and tube formation in vitro in response to VEGF and provoked abnormal cell motility and actin cytoskeleton alterations in isolated endothelial cells. As only one of them (B11) competed for binding of ephrinB2 to EphB4, these data suggest an EphB-receptor–independent blocking mechanism. Anti-ephrinB2 therapy reduced VEGF-induced neovascularization in a mouse Matrigel plug assay. Moreover, systemic administration of ephrinB2-blocking Abs caused a drastic reduction in the number of blood and lymphatic vessels in xenografted mice and a concomitant reduction in tumor growth. Our results show for the first time that specific Ab-based ephrinB2 targeting may represent an effective therapeutic strategy to be used as an alternative or in combination with existing antiangiogenic drugs for treating patients with cancer and other angiogenesis-related diseases.
Adaptive evolution and functional constraint at TLR4 during the secondary aquatic adaptation and diversification of cetaceans
Authors: Shen Tong , Xu Shixia , Wang Xiaohong , Yu Wenhua , Zhou Kaiya , Yang Guang
Published: March 2012

Background

Cetaceans (whales, dolphins and porpoises) are a group of adapted marine mammals with an enigmatic history of transition from terrestrial to full aquatic habitat and rapid radiation in waters around the world. Throughout this evolution, the pathogen stress-response proteins must have faced challenges from the dramatic change of environmental pathogens in the completely different ecological niches cetaceans occupied. For this reason, cetaceans could be one of the most ideal candidate taxa for studying evolutionary process and associated driving mechanism of vertebrate innate immune systems such as Toll-like receptors (TLRs), which are located at the direct interface between the host and the microbial environment, act at the first line in recognizing specific conserved components of microorganisms, and translate them rapidly into a defense reaction.

Results

We used TLR4 as an example to test whether this traditionally regarded pattern recognition receptor molecule was driven by positive selection across cetacean evolutionary history. Overall, the lineage-specific selection test showed that the dN/dS (ω) values along most (30 out of 33) examined cetartiodactylan lineages were less than 1, suggesting a common effect of functional constraint. However, some specific codons made radical changes, fell adjacent to the residues interacting with lipopolysaccharides (LPS), and showed parallel evolution between independent lineages, suggesting that TLR4 was under positive selection. Especially, strong signatures of adaptive evolution on TLR4 were identified in two periods, one corresponding to the early evolutionary transition of the terrestrial ancestors of cetaceans from land to semi-aquatic (represented by the branch leading to whale + hippo) and from semi-aquatic to full aquatic (represented by the ancestral branch leading to cetaceans) habitat, and the other to the rapid diversification and radiation of oceanic dolphins.

Conclusions

This is the first study thus far to characterize the TLR gene in cetaceans. Our data present evidences that cetacean TLR4 has undergone adaptive evolution against the background of purifying selection in response to the secondary aquatic adaptation and rapid diversification in the sea. It is suggested that microbial pathogens in different environments are important factors that promote adaptive changes at cetacean TLR4 and new functions of some amino acid sites specialized for recognizing pathogens in dramatically contrasted environments to enhance the fitness for the adaptation and survival of cetaceans.
The complete genome sequence of the acarbose producer Actinoplanes sp. SE50/110
Authors: Schwientek Patrick , Szczepanowski Rafael , Rückert Christian , Kalinowski Jörn , Klein Andreas , Selber Klaus , Wehmeier Udo F , Stoye Jens , Pühler Alfred
Published: March 2012

Background

Actinoplanes sp. SE50/110 is known as the wild type producer of the alpha-glucosidase inhibitor acarbose, a potent drug used worldwide in the treatment of type-2 diabetes mellitus. As the incidence of diabetes is rapidly rising worldwide, an ever increasing demand for diabetes drugs, such as acarbose, needs to be anticipated. Consequently, derived Actinoplanes strains with increased acarbose yields are being used in large scale industrial batch fermentation since 1990 and were continuously optimized by conventional mutagenesis and screening experiments. This strategy reached its limits and is generally superseded by modern genetic engineering approaches. As a prerequisite for targeted genetic modifications, the complete genome sequence of the organism has to be known.

Results

Here, we present the complete genome sequence of Actinoplanes sp. SE50/110 [GenBank:CP003170], the first publicly available genome of the genus Actinoplanes, comprising various producers of pharmaceutically and economically important secondary metabolites. The genome features a high mean G + C content of 71.32% and consists of one circular chromosome with a size of 9,239,851 bp hosting 8,270 predicted protein coding sequences. Phylogenetic analysis of the core genome revealed a rather distant relation to other sequenced species of the family Micromonosporaceae whereas Actinoplanes utahensis was found to be the closest species based on 16S rRNA gene sequence comparison. Besides the already published acarbose biosynthetic gene cluster sequence, several new non-ribosomal peptide synthetase-, polyketide synthase- and hybrid-clusters were identified on the Actinoplanes genome. Another key feature of the genome represents the discovery of a functional actinomycete integrative and conjugative element.

Conclusions

The complete genome sequence of Actinoplanes sp. SE50/110 marks an important step towards the rational genetic optimization of the acarbose production. In this regard, the identified actinomycete integrative and conjugative element could play a central role by providing the basis for the development of a genetic transformation system for Actinoplanes sp. SE50/110 and other Actinoplanes spp. Furthermore, the identified non-ribosomal peptide synthetase- and polyketide synthase-clusters potentially encode new antibiotics and/or other bioactive compounds, which might be of pharmacologic interest.
Histone deacetylase activity is decreased in peripheral blood monocytes in patients with COPD
Authors: Chen Yanwei , Huang Ping , Ai Wen , Li Xiaoli , Guo Wei , Zhang Jingnong , Yang Jiong
Published: March 2012

Background

Histone deacetylase (HDAC) is an enzyme that regulates chromatin structure and inflammatory gene expression. In patients with chronic obstructive pulmonary disease (COPD), while accumulating evidence indicates that the activity of HDAC is decreased in lung tissue alveolar macrophages, HDAC activity in peripheral inflammatory cells has not yet been evaluated in detail.

Methods

HDAC activities in peripheral blood mononuclear cells (PBMC) were investigated in patients with stable COPD (n = 26), non-smoking controls (n = 13), and smoking controls (n = 10), respectively. HDAC activity was measured using an HDAC Activity/Inhibitor Screening Assay Kit. Serum interleukine-8 (CXCL8) levels were determined by ELISA techniques. Lung function test was carried out according to the ATS/ERS guidelines.

Results

Compared with healthy non-smokers, HDAC activity in the PBMCs of COPD patients was decreased by 40% (13.06 ± 5.95 vs. 21.39 ± 4.92 (μM/μg), p < 0.001). In patients with COPD, HDAC activity was negatively correlated to smoke intensity (r = -0.867, p < 0.001). In COPD patients who had smoked for more than 40 pack-years, HDAC activity in PBMC was 40% lower than that in COPD patients who had smoked fewer than 40 pack-years.

Moreover, serum CXCL8 levels in patients with COPD were significantly higher than that in controls and were negatively correlated to HDAC activities.

Conclusion

In patients with COPD, HDAC activity in the PBMCs is lower than that in healthy controls. The reduction of HDAC activity may be associated with smoking exposure through inflammatory pathways.
Evaluation of CACC string stability using SUMO, Simulink, and OMNeT++
Authors: Lei Chenxi , van Eenennaam Emiel Martijn , Klein Wolterink Wouter , Ploeg Jeroen , Karagiannis Georgios , Heijenk Geert
Published: March 2012

Recent development in wireless technology enables communication between vehicles. The concept of co-operative adaptive cruise control (CACC)--which uses wireless communication between vehicles--aims at string stable behavior in a platoon of vehicles. "String stability" means any non-zero position, speed, and acceleration errors of an individual vehicle in a string do not amplify when they propagate upstream. In this article, we will discuss the string stability of CACC and evaluate its performance under varying packet loss ratios, beacon sending frequencies, and time headway settings in simulation experiments. The simulation framework is built up with a controller prototype, a traffic simulator, and a network simulator.
Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy
Authors: Dees Ellen , Miller Paul M. , Moynihan Katherine L. , Pooley Ryan D. , Hunt R. Pierre , Galindo Cristi L. , Rottman Jeffrey N. , Bader David M.
Published: March 2012

CENP-F is a large multifunctional protein with demonstrated regulatory roles in cell proliferation, vesicular transport and cell shape through its association with the microtubule (MT) network. Until now, analysis of CENP-F has been limited to in vitro analysis. Here, using a Cre-loxP system, we report the in vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type displaying high levels of CENP-F expression. Loss of CENP-F function in developing myocytes leads to decreased cell division, blunting of trabeculation and an initially smaller, thin-walled heart. Still, embryos are born at predicted mendelian ratios on an outbred background. After birth, hearts lacking CENP-F display disruption of their intercalated discs and loss of MT integrity particularly at the costamere; these two structures are essential for cell coupling/electrical conduction and force transduction in the heart. Inhibition of myocyte proliferation and cell coupling as well as loss of MT maintenance is consistent with previous reports of generalized CENP-F function in isolated cells. One hundred percent of these animals develop progressive dilated cardiomyopathy with heart block and scarring, and there is a 20% mortality rate. Importantly, although it has long been postulated that the MT cytoskeleton plays a role in the development of heart disease, this study is the first to reveal a direct genetic link between disruption of this network and cardiomyopathy. Finally, this study has broad implications for development and disease because CENP-F loss of function affects a diverse array of cell-type-specific activities in other organs.
Behavior of Circular Reinforced Concrete Columns Under Fire Conditions
Authors: Raut Nikhil , Kodur Venkatesh
Published: March 2012

A numerical model was developed for tracing the behavior of circular reinforced concrete (RC) columns over the entire range of loading from pre-fire conditions to collapse under fire. The macroscopic finite element based model utilizes time dependant moment-curvature relations of various column segments and the analysis is carried out in three stages; namely, establishing fire temperatures, calculating the heat transfer through the structure, and then carrying out strength analysis. The model, which accounts for high temperature nonlinear material properties, is capable of predicting the fire resistance of circular RC columns under realistic fire scenarios, loading conditions, and failure criteria. The validity of the model is established by comparing predictions from the computer program with results from full-scale fire resistance tests. The validated model is applied to undertake a set of parametric studies to quantify the effect of column size, load level, load eccentricity, and concrete strength on the fire resistance of RC columns. Results generated from parametric studies are utilized to develop a simplified equation for evaluating the fire resistance of circular RC columns. Fire resistance predictions from the proposed equation are in good agreement with those obtained from fire tests and nonlinear finite element analysis.