bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of CDKN2A (p16) promoter methylation and loss of expression in 902 colorectal cancers: Cohort study and literature review
Authors: Shima Kaori , Nosho Katsuhiko , Baba Yoshifumi , Cantor Mami , Meyerhardt Jeffrey A. , Giovannucci Edward L. , Fuchs Charles S. , Ogino Shuji
Published: May 2010

A cyclin‐dependent kinase inhibitor CDKN2A (p16/Ink4a) is a tumor suppressor and upregulated in cellular senescence. CDKN2A promoter methylation and gene silencing are associated with the CpG island methylator phenotype (CIMP) in colon cancer. However, prognostic significance of CDKN2A methylation or loss of CDKN2A (p16) expression independent of CIMP status remains uncertain. Using a database of 902 colorectal cancers in 2 independent cohort studies (the Nurses' Health Study and the Health Professionals Follow‐up Study), we quantified CDKN2A promoter methylation and detected hypermethylation in 269 tumors (30%). By immunohistochemistry, we detected loss of CDKN2A (p16) expression in 25% (200/804) of tumors. We analyzed for LINE‐1 hypomethylation and hypermethylation at 7 CIMP‐specific CpG islands (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); microsatellite instability (MSI); KRAS, BRAF and PIK3CA mutations; and expression of TP53 (p53), CTNNB1 (β‐catenin), CDKN1A (p21), CDKN1B (p27), CCND1 (cyclin D1), FASN (fatty acid synthase) and PTGS2 (cyclooxygenase‐2). CDKN2A promoter methylation and loss of CDKN2A (p16) were associated with shorter overall survival in univariate Cox regression analysis [hazard ratio (HR): 1.36, 95% CI: 1.10–1.66, p = 0.0036 for CDKN2A methylation; HR: 1.30, 95% CI: 1.03–1.63, p = 0.026 for CDKN2A (p16) loss] but not in multivariate analysis that adjusted for clinical and tumor variables, including CIMP, MSI and LINE‐1 methylation. Neither CDKN2A promoter methylation nor loss of CDKN2A (p16) was associated with colorectal cancer‐specific mortality in uni‐ or multivariate analysis. Despite its well‐established role in carcinogenesis, CDKN2A (p16) promoter methylation or loss of expression in colorectal cancer is not independently associated with patient prognosis.
“Ghosts in the Nursery:” Infant sleep and sleep‐related cognitions of parents raised under communal sleeping arrangements
Authors: Tikotzky Liat , Sharabany Ruth , Hirsch Idit , Sadeh Avi
Published: May 2010

In an experiment of nature, a normal cohort of parents who were raised under communal sleeping arrangements (CSA) in Israeli kibbutzim are raising their infants at home under home‐based family sleeping arrangements. The present study focused on exploring the links between the early sleep experiences of CSA parents and their present sleep‐related beliefs and behaviors. In particular, the study assessed whether the cognitions of CSA parents regarding infant sleep differ from cognitions of parents who were raised under home‐based family sleeping arrangements. Furthermore, parental soothing methods and infant sleep patterns were compared. One hundred forty‐one families participated in this study. The children's ages ranged between 4.5 to 30 months. Parental cognitions were evaluated by two questionnaires. Infant sleep was assessed by a questionnaire and by daily parental reports. As expected, CSA parents were more likely than were control parents to: (a) interpret infant night wakings as a sign of distress and (b) actively soothe their infants at bedtime, co‐sleep with them, and report more night wakings of their infants. These findings support the hypothesis that early childhood sleep‐related experiences of parents (“Ghosts in the Nursery”) influence their parental sleep‐related cognitions that in turn affect infant sleep patterns.
Cardiac progenitor cells: Potency and control
Authors: Di Nardo Paolo , Forte Giancarlo , Ahluwalia Arti , Minieri Marilena
Published: May 2010

Stem cell‐based regeneration of the heart has focused much scientific and public attention being cardiac diseases the major cause of disability and death in industrialized countries. Innumerable efforts have been taken to unveil the mechanisms undergoing stem cell proliferation and fate, but much remains to be endeavoured for their application in clinical practice. Nevertheless, the discovery of progenitor cells resident within the cardiac tissue has sparked off enthusiasm about the possibility of efficiently and safely engineering them to repair the injured myocardium. Indeed, the early applications of the cardiac progenitor cells, mostly based on simplistic concepts and techniques, have failed highlighting the prerequisite of expanding the knowledge about progenitor cell features and microenvironmental conditioning. In this review, recent information on resident cardiac progenitor cells has been systematically gathered in order to create a valuable instrument to support investigators in their efforts to establish an efficient cardiac cell therapy. J. Cell. Physiol. 224: 590–600, 2010. © 2010 Wiley‐Liss, Inc.
Redistribution of mitochondria leads to bursts of ATP production during spontaneous mouse oocyte maturation
Authors: Yu Yuansong , Dumollard Remi , Rossbach Andreas , Lai F. Anthony , Swann Karl
Published: May 2010

During mammalian oocyte maturation there are marked changes in the distribution of mitochondria that supply the majority of the cellular ATP. Such redistribution of mitochondria is critical for oocyte quality, as oocytes with a poor developmental potential display aberrant mitochondrial distribution and lower ATP levels. Here we have investigated the dynamics of mitochondrial ATP production throughout spontaneous mouse oocyte maturation, using live measurements of cytosolic and mitochondrial ATP levels. We have observed three distinct increases in cytosolic ATP levels temporally associated with discrete events of oocyte maturation. These changes in cytosolic ATP levels are mirrored by changes in mitochondrial ATP levels, suggesting that mitochondrial ATP production is stimulated during oocyte maturation. Strikingly, these changes in ATP levels correlate with the distribution of mitochondria undergoing translocation to the peri‐nuclear region and aggregation into clusters. Mitochondrial clustering during oocyte maturation was concomitant with the formation of long cortical microfilaments and could be disrupted by cytochalasin B treatment. Furthermore, the ATP production bursts observed during oocyte maturation were also inhibited by cytochalasin B suggesting that mitochondrial ATP production is stimulated during oocyte maturation by microfilament‐driven, sub‐cellular targeting of mitochondria. J. Cell. Physiol. 224: 672–680, 2010. © 2010 Wiley‐Liss, Inc.
N‐terminal interaction domain implicates PAK4 in translational regulation and reveals novel cellular localization signals
Authors: Baldassa Simona , Calogero Alessandra Maria , Colombo Graziano , Zippel Renata , Gnesutta Nerina
Published: May 2010

The serine/threonine kinase PAK4 is a Rho GTPases effector protein implicated in many critical biological processes, including regulation of cell morphology and motility, embryonic development, cell survival, response to infection, and oncogenic transformation. Consistently with its pro‐oncogenic features, PAK4 was found to be overexpressed in many cancer cell lines and tissues, and to be necessary to promote activation of survival pathways. PAK4, like other Paks, is now considered a promising target for specific therapy. Little is known on its modes of regulation, molecular partners, and substrates. Because the N‐terminal regulatory moiety plays important roles in PAK4 activity and functions, even independently of GTPase interactions, in this study we employed an affinity chromatography approach to identify N‐terminal domain binding partners. Within this protein region we identified a novel interaction domain involved in association with ribonucleoprotein (RNP) complexes, suggesting PAK4 implications in translational regulation. Indeed, we found that active PAK4 can affect (cap‐independent) translation from specific IRES sequences in vivo, and that the N‐terminal domain is critical for this regulation. Further, we could establish that within the RNP interacting sequence PAK4 regulatory domain contains targeting elements that drive cytoplasmic localization and act as nuclear export signal. Functional implication of endogenous PAK4 protein, which was found in both cytoplasmic and nuclear fractions, in IRES‐mediated translation further underlines the significance of the reported findings. Our data reveal novel means for PAK4 regulation of gene expression, and provide new elements to understand the molecular mechanisms that determine PAK4 cellular localization and functions. J. Cell. Physiol. 224: 722–733, 2010. © 2010 Wiley‐Liss, Inc.
An approach to optimization of enzymatic hydrolysis from sugarcane bagasse based on organosolv pretreatment
Authors: Mesa Leyanis , González Erenio , Cara Cristóbal , Ruiz Encarnación , Castro Eulogio , Mussatto Solange I.
Published: May 2010

BACKGROUND: The organosolv pretreatment followed by enzymatic hydrolysis of the pretreated material and subsequent fermentation of the hydrolysate produced, was the strategy used for ethanol production from sugarcane bagasse. The effect of different operational variables affecting the pretreatment (the catalyst type and its concentration, and the pretreatment time) and enzymatic hydrolysis stage (substrate concentration, cellulase loading, addition of xylanase and Tween 20, and the cellulase/β‐glucosidase ratio), were investigated.

RESULTS: The best values of glucose concentration (28.8 g L−1) and yield (25.1 g per 100 g dry matter) were obtained when the material was pretreated with 1.25% (w/w) H2SO4 for 60 min, and subsequently hydrolyzed using 10% (w/v) substrate concentration in a reaction medium supplemented with xylanase (300 UI g−1) and Tween 20 (2.5% w/w). Fermentation of the broth obtained under these optimum conditions by Saccharomyces cerevisiae resulted in an ethanol yield of 92.8% based on the theoretical yield, after 24 h.

CONCLUSION: Organosolv pretreatment of sugarcane bagasse under soft conditions, and subsequent enzymatic hydrolysis of the pretreated material with a cellulolytic system supplemented with xylanase and Tween 20, is a suitable procedure to obtain a glucose rich hydrolysate efficiently fermentable to ethanol by Sacharomyces cerevisiae yeasts. Copyright © 2010 Society of Chemical Industry
The thoracic muscular system and its innervation in third instar Calliphora vicina Larvae. I. Muscles of the pro‐ and mesothorax and the pharyngeal complex
Authors: Hanslik Ulrike , Schoofs Andreas , Niederegger Senta , Heinzel Hans‐Georg , Spieß Roland
Published: May 2010

An anatomical description is given by the muscles in the pro‐ and mesothorax, and those associated with the feeding apparatus (cephalopharyngeal skeleton, CPS) that participate in feeding behavior in third instar Calliphora larvae. The body wall muscles in the pro‐ and mesothoracic segments are organized in three layers: internal, intermedial, and external. The muscles were labeled with roman numerals according to the nomenclature in use for the abdominal segments. Muscles associated with the CPS are labeled according to their function. The prothorax bears five pairs of lateral symmetrically longitudinal segmental body wall muscles and lacks the transversal muscle group present in the mesothorax and abdominal segments. Additionally, four pairs of intersegmental muscles project from the prothorax to the second, fourth, and fifth segment. The mesothorax bears 15 pairs of segmental longitudinal and 18 pairs of transversal muscles. The accessory pharyngeal muscles span the CPS and the cuticle. Three pairs of protractors and retractors and two pairs of mouth hook accessors (MHAC) exist, which move the CPS relative to the body. The pharyngeal muscles are exclusively attached to the structures of the CPS. The mouth hook elevators and depressors, which mediate the hooks rotation are attached to the ventral arm of the CPS and project to a dorsal (elevators) or ventral (depressors) protuberance of the mouth hooks. The cibarial dilator muscles (CDM) span the dorsal arms of the CPS and the dorsal surface of the esophagus and mediate food ingestion. The labial retractors (LRs) lack antagonists and project from the ventral surface of the CPS to the unpaired labium. Contractions of these muscles open the mouth cavity. J. Morphol. 271:960–968, 2010. © 2010 Wiley‐Liss, Inc.
A fibrous membrane suspends the multifocal lens in the eyes of lampreys and African lungfishes
Authors: Gustafsson Ola S.E. , Ekström Peter , Kröger Ronald H.H.
Published: May 2010

The sharpness and thus information content of the retinal image in the eye depends on the optical quality of the lens and its accurate positioning in the eye. Multifocal lenses create well‐focused color images and are present in the eyes of all vertebrate groups studied to date (mammals, reptiles including birds, amphibians, and ray‐finned fishes) and occur even in lampreys, i.e., the most basal vertebrates with well‐developed eyes. Results from photoretinoscopy obtained in this study indicate that the Dipnoi (lungfishes), i.e., the closest piscine relatives to tetrapods, also possess multifocal lenses. Suspension of the lens is complex and sophisticated in teleosts (bony fishes) and tetrapods. We studied lens suspension using light and electron microscopy in one species of lamprey (Lampetra fluviatilis) and two species of African lungfish (Protopterus aethiopicus aethiopicus and Protopterus annectens annectens). A fibrous and highly transparent membrane suspends the lens in both of these phylogenetically widely separated vertebrate groups. The membrane attaches to the lens approximately along the lens equator, from where it extends to the ora retinalis. The material forming the membrane is similar in ultrastructure to microfibrils in the zonule fibers of tetrapods. The membrane, possibly in conjunction with the cornea, iris, and vitreous body, seems suitable for keeping the lens in the correct position for well‐focused imaging. Suspension of the lens by a multitude of zonule fibers in tetrapods may have evolved from a suspensory membrane similar to that in extant African lungfishes, a structure that seems to have appeared first in the lamprey‐like ancestors of allextant vertebrates. J. Morphol. 271:980–989, 2010. © 2010 Wiley‐Liss, Inc.
Direct analysis of the central panel of the so‐called Wyts triptych after Jan van Eyck
Authors: Deneckere A. , Hocquet F.‐Ph. , Born A. , Klein P. , Rakkaa S. , Lycke S. , De Langhe K. , Martens M. P. J. , Strivay D. , Vandenabeele P. , Moens L.
Published: May 2010

The applicability of mobile, non‐destructive techniques such as energy dispersive X‐ray fluorescence spectroscopy, which reveals the elemental composition, and fibre‐coupled Raman spectroscopy, offering molecular information, is applied to the central panel of the Wyts triptych, after Jan van Eyck. Using a combination of these direct techniques, vermilion (HgS), lead white (2PbCO3·Pb(OH)2), anatase (TiO2), massicot (PbO), zinc white (ZnO) and lead‐tin yellow type I (Pb2SnO4) could be identified. X‐ray fluorescence spectroscopy (XRF) measurements also confirmed the presence of cobalt. Also, copper was detected in different blue and green areas. For the brown and red colour, iron oxides were used. Apart from identifying pigments, the combination of these analytical techniques also gave information about restored parts and the layered structure of the panel. XRF maps of three different areas of the panel painting were recorded to get an idea of the changes the painting underwent during its past history. This research confirms the results of the visual analysis that the painting is a heavily restored copy of a lost original by Jan van Eyck. Copyright © 2010 John Wiley & Sons, Ltd.
Development of a validated liquid chromatographic method for the determination of related substances and assay of tenofovir disoproxil fumarate
Authors: Ashenafi Dunge , Chintam Varalaxmi , van Veghel Daisy , Dragovic Sanja , Hoogmartens Jos , Adams Erwin
Published: May 2010

The present study describes the development and validation of a selective liquid chromatographic (LC) method for the analysis of tenofovir disoproxil fumarate (TDF) and its related substances. The gradient method uses a base deactivated C18 column (Hypersil BDS column; 25 cm×4.6 mm I.D.) maintained at a temperature of 30°C. The mobile phases consist of acetonitrile, tetrabutylammonium/phosphate buffer pH 6.0 and water: (A; 2:20:78 v/v/v) and (B; 65:20:15 v/v/v). The flow rate is 1.0 mL/min and UV detection is performed at 260 nm. Good separation of TDF and 21 impurities was achieved. A system suitability test (SST) to check the quality of separation is also specified. The developed method was further validated with respect to robustness, precision, sensitivity and linearity. The method is proved to be robust, precise, sensitive and linear between 0.1 μg/mL and 0.15 mg/mL. The limit of detection and limit of quantification are 0.03 and 0.1 μg/mL, respectively. The method was successfully applied to the quantification of related substances and assay of commercial TDF samples (bulk substances and tablets).
Lower airways may also be affected in asymptomatic patients with recent onset of allergic rhinitis
Authors: Ciprandi Giorgio , Cirillo Ignazio , Klersy Catherine
Published: May 2010

Objectives/Hypothesis:

It is well known that there is a close association between allergic rhinitis (AR) and asthma, and AR is a strong risk factor for the onset of asthma. AR duration is significantly associated with a possible bronchial involvement. The aim of this study was to investigate the presence of possible spirometric abnormalities and bronchial hyperreactivity (BHR) in a large group of patients with recent onset of AR.

Study Design:

Observational cross‐sectional study.

Methods:

A total of 1,539 AR patients were consecutively evaluated. Clinical examination, skin prick test, spirometry, and methacholine challenge were performed on all patients.

Results:

There were 362 (23%) patients with FEF25–75 values <70% of predicted. The methacholine challenge was positive in 74.43% of patients, and 72.22% of the population presented a polysensitization. At multivariable analysis, an FEV1 value lower than 92% of predicted, as well as increasing severity of BHR and polysensitization appeared to be independent predictors of a reduced FEF25–75 value.

Conclusions:

This study shows that reduced FEF25–75 values may be present in some patients with recent onset of AR. FEV1 <92%, severity of BHR, and polysensitization may be considered risk factor for this phenomenon. Laryngoscope, 2010.
Influence of topical antifungal drugs on ciliary beat frequency of human nasal mucosa
Authors: Hofmann Thiemo , Reinisch Sabine , Gerstenberger Claus , Koele Wolfgang , Gugatschka Markus , Wolf Gerald
Published: May 2010

Objectives/Hypothesis:

Topical antifungal treatment is a subject of discussion in the treatment of chronic rhinosinusitis. The aim of this research was to study the effects of antifungal drugs on ciliary beat frequency (CBF) of human nasal mucosa under in vitro conditions.

Study Design:

Case series of in vitro experiments and in vitro study of cultured ciliated cells of human nasal mucosa.

Methods:

Human nasal mucosa was acquired during routine endoscopic sinus surgery. Cells were cultivated on object slides and exposed to different antifungal drugs in a newly developed test system. This system allowed continuous and reproducible exposure to different drugs at constant temperature, pH value, and osmolarity. The drugs were amphotericin B in two different concentrations and itraconazole.

Results:

Rinsing with higher concentrations of amphotericin B led to an immediate decrease of CBF, with a total stop after 15 minutes. A different result was seen in the group with lower concentrations; CBF decreased again quickly after rinsing with the test drug, but all of them recovered after rinsing with neutral solution. When using itraconazole a decline in CBF was observed again; one half of the samples returned to activity.

Conclusions:

Our in vitro results demonstrate a dose‐dependent effect of the antifungal drugs amphotericin B and itraconazole on ciliary beat frequency of human nose epithelium. Laryngoscope, 2010
Taste disturbance following tonsillectomy–a prospective study
Authors: Heiser Clemens , Landis Basile N. , Giger Roland , Cao Van Helene , Guinand Nils , Hörmann Karl , Stuck Boris A.
Published: May 2010

Objectives/Hypothesis:

Persistent taste disturbance is a rare complication after tonsillectomy and mainly documented by case reports or a few retrospective and prospective trials with a limited number of patients. None could clarify frequency, time course, or prognosis of long‐lasting dysgeusia after tonsillectomy. The aim of the study was to provide a symptom‐based follow‐up after tonsillectomy to assess postoperative taste disorders.

Study Design:

Prospective clinical trial.

Methods:

From December 2007 to June 2009 adult patients undergoing tonsillectomy were asked to take part in the trial. Two hundred twenty‐three patients (119 female, 104 male; mean age, 33 ± 13 years) were included. The day prior to surgery, and 2 weeks and 6 months after tonsillectomy a standardized questionnaire was completed by patients. The questionnaire focused on taste function, taste disorders, pain, foreign body sensation, and bleeding episodes after tonsillectomy.

Results:

One hundred eighty‐eight (2 weeks) and 181 (6 months) patients returned the questionnaires. Thirty‐two percent (n = 60) of patients reported taste disorders after tonsillectomy 2 weeks postoperatively and 15 patients (8%) at 6‐month follow‐up. Metallic and bitter parageusia were most frequently reported. The mean ratings of gustatory function were significantly lower 2 weeks after surgery (P < .001) and reached preoperative values 6 months after surgery. Almost 30% of patients reported postoperative bleeding, 10% long‐lasting postoperative pain, and 20% foreign body sensation.

Conclusions:

Long‐lasting taste disturbance (metallic and bitter parageusia) after tonsillectomy is more frequent than previously reported. Long‐lasting pain and foreign body sensation seem to be common symptoms. With regard to these results, a thorough preoperative explanation is mandatory. Laryngoscope, 2010
Three‐dimensional arytenoid movement induced by vocal fold injections
Authors: Mau Ted , Weinheimer Kent T.
Published: May 2010

Objectives/Hypothesis:

To quantitatively characterize arytenoid movement induced by vocal fold injection augmentation in an excised larynx model.

Study Design:

Laboratory and computational.

Methods:

Vocal folds of human cadaveric larynges were injected with calcium hydroxylapatite. High‐resolution computed tomography scans were obtained before and after injection. Densities corresponding to the arytenoid and cricoid cartilages were extracted and processed with custom MATLAB routines to generate selective three‐dimensional reconstructions of the larynx. Pre‐ and postinjection positions of the arytenoid were compared.

Results:

Vocal fold injections resulted in predominantly small‐magnitude medial rotation and medial translation of the arytenoid. Movements in other directions as would be expected in physiologic adduction were not observed.

Conclusions:

Vocal fold injection augmentation induced passive movement of the arytenoid that has not been described previously. This movement does not reproduce the trajectory of physiologic adduction. This finding has implications for the treatment of unilateral vocal fold paralysis without arytenoid repositioning maneuvers. Laryngoscope, 2010
Ischemic necrosis of the tongue in patients with cardiogenic shock
Authors: Roman Benjamin R. , Immerman Sara B. , Morris Luc G. T.
Published: May 2010

Objectives/Hypothesis:

Ischemic necrosis of the tongue is a rare entity generally associated with vasculitis. Critically ill patients with shock might experience hypoperfusion of head and neck end organs including the tongue.

Study Design:

Retrospective analysis of hospital charts.

Methods:

Case histories and photographs of five patients who developed ischemic tongue necrosis in the context of cardiogenic shock.

Results:

Five critically ill patients in our institution's cardiothoracic intensive care unit developed ischemic necrosis of the tongue. All five patients experienced protracted courses of profound cardiogenic shock requiring high‐dose vasopressor support and urgent cardiac surgery. Three patients required intra‐aortic balloon pumps. All patients had concomitant signs of poor end organ perfusion, including lower extremity ischemia and renal and hepatic failure. Ultimately, four of five patients died, with one patient surviving after sloughing of the entire oral tongue.

Conclusions:

Ischemic necrosis of the oral tongue is an uncommon but perhaps under‐reported manifestation of end organ hypoperfusion in shock, likely signifying poor prognosis. Laryngoscope, 2010
Biomechanics of the deformity of septal L‐Struts
Authors: Lee Shu Jin , Liong Kyrin , Tse Kwong Ming , Lee Heow Pueh
Published: May 2010

Objectives/Hypothesis:

A septal L‐strut is often preserved or created during septoplasty. The main intention is to provide structural stability and to straighten the nasal septum. Deformity or excessive deformation of the L‐strut might cause functional or aesthetic complications. The objectives were to examine the effects of material properties, the boundary conditions, the nasal tip support, and the geometry of the L‐struts on the deformity of septal L‐struts.

Study Design:

Computer‐aided modeling was used to create a spring‐supported nasal tip and free nasal tip L strut septal cartilage models upon which simulation was performed to analyse the deformation patterns.

Methods:

A five‐sided septum model was first created from the computed tomography scan of a human subject. Several models with various combinations of wider or narrower dorsal struts as well as arc of cartilage were then constructed from this septum model. The edges connected to bony supports were assumed to be fixed, and the nasal tip was assumed to be spring supported. Finite element analyses were carried out to determine the deformation and stress distribution in the septal strut for different combinations of material properties and nasal tip spring support.

Results:

The spring‐supported nasal tip model provides a more accurate representation of the boundary conditions in the nose. In both the free and spring‐supported nasal tips—the BC junction and the nasal spine are found to be the consistent points of maximum stress regardless of material properties. The preservation of an arc of cartilage and a wider dorsal strut increase the stability of the structure.

Conclusions:

The introduction of a spring‐supported nasal tip model provided a more accurate representation of the boundary conditions in the nose. The bony‐cartilaginous junction and the nasal spine were found to be the consistent points of maximum stress, regardless of material properties. The preservation of an arc of cartilage and a wider dorsal strut increased the stability of the structure. Laryngoscope, 2010
Flexible cochlear microendoscopy in the gerbil
Authors: Campbell Adam P. , Suberman Thomas A. , Buchman Craig A. , Fitzpatrick Douglas C. , Adunka Oliver F.
Published: May 2010

Objectives/Hypothesis:

To validate the scientific utility of flexible cochlear microendoscopy in the gerbil. This model is currently being developed to study the effects of intracochlear electrode positioning on functional parameters.

Study Design:

Animal experiments.

Methods:

A flexible fiberoptic microendoscope featuring a light channel and an outer diameter of 0.4 mm was specially modified to allow intracochlear visualization. Specifically, the focus distance was reduced to 1 mm and the optical properties were modified so that visualization was adequate when submerged in perilymphatic fluid. This endoscope was used to view intracochlear contents and monitor the progress of electrode insertions in 11 gerbils. The endoscopic data estimating the site of damage were compared to postmortem microdissections.

Results:

The endoscope allowed for adequate visualization of intracochlear content in all animals. The site of electrode contact seen in the endoscope was confirmed in the microdissected cochleae in 10 of 11 cases, indicating the endoscope's ability to correctly identify the site of intracochlear trauma in this animal model.

Conclusions:

The current report demonstrates the feasibility of intracochlear microendoscopy in an animal model of hearing preservation cochlear implantation. Laryngoscope, 2010
Development of a calcium alginate tympanostomy tube
Authors: Sherman Ethan G. , Antonelli Patrick J. , Tran‐Son‐Tay Roger
Published: May 2010

Objectives/Hypothesis:

Tympanostomy tubes (TTs) are prone to complications resulting in part from the unpredictable duration that the TT remains in the tympanic membrane. General anesthesia may be necessary to remove TTs that fail to extrude. The purpose of this study was to develop a TT that could be dissolved on demand but remain functional with exposure to common otologic exposures.

Study Design:

Prospective in vitro analysis.

Methods:

Dissolvable TTs were developed from calcium alginate. Mechanical properties and occlusion susceptibility were optimized by varying ingredient concentrations and compared to commonly used commercial TTs using in vitro measures.

Results:

Alginate TTs had a greater compressive strength than commercial silicone tubes. TTs composed of 0.5 M CaCl were stronger than high molarity CaCl concentrations. Uncoated alginate TTs showed a 20% reduction in occlusion propensity. Exposure of alginate TTs to otological solutions for 24 hours resulted in degradation of their mechanical properties, but they remained superior to commercial silicone TTs.

Conclusions:

Alginate TTs appear to be a good alternative to commercial tubes based on high mechanical strength and low occlusion propensity. Furthermore, unlike commercial TTs, alginate TTs have the potential to be dissolved in vivo if retained. Laryngoscope, 120:2473–2477, 2010
Pluviometric gradient incidence and the hydrological behaviour of soil surface components (southern Spain)
Authors: Ruiz Sinoga J. D. , Garcia Marín R. , Martínez‐Murillo J. F. , Gabarrón Galeote M. A.
Published: May 2010

The hydrological response of Mediterranean hillslopes depends on the type of soil surface components (SSC) which is controlled by the strongly climate. Along a Mediterranean climatic gradient, the type of soil surface component is modified as the aridity increases: biotic ones (annual plants, litter, moss and lichens) used to be more significant under humid climatic conditions, whereas abiotic ones (crusts, rock fragments and outcrops), under semiarid conditions. The aim of the study is to analyse the hydrological behaviour of different types of SSC in three field sites under different Mediterranean climatic conditions to (1) confirm whether the pluviometric gradient factor affects their hydrological response, and (2) whether, in each field site, SSC play the same role as controlling factors of infiltration processes. The method is based on grouping explanatory variables (related to precipitations, topography, vegetal cover, soil moisture and some soil physical, chemical and hydrological properties) through factorial analysis being applied for both regional and local approaches. The results confirm that the type of soil surface component acts as regulator of soil hydrological processes along the pluviometric gradient as well as at every field site, and show that the role played by the type of soil surface component is a much more significant key‐factor for the hydrological response of soils under dry‐Mediterranean climatic conditions. Copyright © 2010 John Wiley & Sons, Ltd.
Comparison of quantitative parameters in cervix cancer measured by dynamic contrast–enhanced MRI and CT
Authors: Yang Cheng , Stadler Walter M. , Karczmar Gregory S. , Milosevic Michael , Yeung Ivan , Haider Masoom A.
Published: May 2010

Cervical tumors of 38 cervix cancer patients were scanned by T1‐weighted dynamic contrast enhanced (DCE) MRI and then by DCE‐CT on the same day. Gadodiamide and iohexol were respectively used as the low‐molecular‐weight contrast agent in DCE‐MRI and DCE‐CT. Under an extended Tofts model, DCE‐MRI data were analyzed using either individual arterial input functions estimated by a multiple reference tissue method or a population arterial input function by Parker et al., whereas DCE‐CT data were analyzed using the arterial input function directly measured from the external iliac arteries. The derived quantitative parameters of cervical tumors were compared between DCE‐MRI and DCE‐CT. When using the individual multiple reference tissue method arterial input functions to analyze the DCE‐MRI data, the correlation coefficients between DCE‐MRI‐ and DCE‐CT‐derived parameters were, respectively, back‐flux rate constant (r = 0.80), extravascular extracellular fractional volume (r = 0.73), contrast agent transfer rate (r = 0.62), and blood plasma volume (r = 0.32); when using the Parker population arterial input function, the correlation coefficients were back‐flux rate constant (r = 0.79), extravascular extracellular fractional volume (r = 0.77), contrast agent transfer rate (r = 0.63), and blood plasma volume (r = 0.58). Tumor parametric maps derived by DCE‐MRI and DCE‐CT had very similar morphologies. However, the means of most derived quantitative parameters were significantly different between the two imaging methods. Close correlation of quantitative parameters derived from two independent imaging modalities suggests both are measuring similar tumor physiologic variables. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Manganese‐enhanced MRI of salivary glands and head and neck tumors in living subjects
Authors: Seshadri Mukund , Hoy Allison
Published: May 2010

Manganese‐enhanced MRI has previously been used for visualization of brain architecture and functional mapping of neural pathways. The present work investigated the potential of manganese‐enhanced MRI for noninvasive imaging of salivary glands in living subjects. Marked shortening of T1 was observed in salivary glands of naïve mice (n = 5) 24–48 h after systemic administration of MnCl2 (0.4 mmol/kg, intraperitoneally). Three‐dimensional MR microscopy confirmed selective contrast enhancement of salivary gland tissues post–MnCl2 injection. Ectopic and orthotopic head and neck tumor xenografts also showed an increase in R1 at 24 h following MnCl2 injection (0.2 mmol/kg, intraperitoneally). However, tumor enhancement was minimal compared to salivary gland tissue. Salivary gland R1 values were lower in mice bearing orthotopic head and neck tumors compared to naïve mice. These results demonstrate, for the first time, the usefulness of manganese‐enhanced MRI in the visualization of salivary glands and head and neck tumors in vivo. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Mentoring fördert Frauen in der Wissenschaft
Authors: Hübenthal Anke
Published: May 2010

Immer mehr professionelle Mentoringprogramme sollen Nachwuchskräften den beruflichen Aufstieg in der Wissenschaft erleichtern. Es gibt Programme, die sich speziell an Frauen richten — in Frankfurt gleich vier davon.
”Für unsere schöne Wissenschaft eine Einigung anzubahnen“
Authors: Mönnich Michael
Published: May 2010

Kongresse sind auch im Zeitalter von Internet und E‐Mail eine wichtige und beliebte Form der Kommunikation innerhalb einer wissenschaftlichen Disziplin. Die Chemie kann auf eine 150‐jährige Tradition zurückblicken: Der erste internationale Chemikerkongress fand vom 3. bis 5. September 1860 in Karlsruhe statt.
Die obersten Schichten genau im Blick
Authors: Nehm Rainer
Published: May 2010

Die noch junge RF‐GD‐TOF‐Massenspektrometrie charakterisiert die Oberflächenschichten von Polymeren, Stählen oder Solarzellen. Die Methode informiert auch über Isotopenverteilung und molekulare Zusammensetzung der Probe.
”The criterion was excellence“
Authors: Guggolz Ernst , Remenyi Christian
Published: May 2010

The 3rd Euchems Conference is an ideal platform for spotlighting chemistry as the key source of sustainable solutions to the mega‐topics and challenges facing all of us today: energy, food supplies, and resources in a healthy environment. Nachrichten aus der Chemie talked with Francois Diederich and Andreas Hirsch, chairs of the Scientific Committee.
Schnell zu Biarylen: Direkte Arylierung mit Arylhalogeniden
Authors: Kirsch Stefan , Harschneck Tobias
Published: May 2010

Kaum ein Feld der organischen Chemie ist in jüngerer Zeit so in Mode gekommen wie die C‐H‐Aktivierung. Insbesondere die direkte Arylierung mit Arylhalogeniden hat einen derart großen Reifegrad erreicht, dass sie zu einer echten Alternative zu klassischen Kreuzkupplungen mit Organometallverbindungen wird. Etliche Biarylverbindungen lassen sich bereits unter milden und experimentell einfachen Reaktionsbedingungen durch direkte Arylierung darstellen.
A family of ANS four‐node exact geometry shell elements in general convected curvilinear coordinates
Authors: Kulikov G. M. , Plotnikova S. V.
Published: May 2010

The non‐conventional exact geometry shell elements based on the Timoshenko–Mindlin kinematics with five displacement degrees of freedom are proposed. The term ‘exact geometry (EXG)’ reflects the fact that coefficients of the first and second fundamental forms of the reference surface and Christoffel symbols are taken exactly at every Gauss integration point. The choice of only displacements as fundamental shell unknowns gives an opportunity to derive strain–displacement relationships, which are invariant under rigid‐body shell motions in a convected curvilinear coordinate system. This paper presents a newly developed family consisting of three hybrid and one displacement‐based four‐node EXG shell elements. To avoid shear and membrane locking and have no spurious zero energy modes, the ANS concept is employed. The ANS interpolations satisfy exactly the plate compatibility equation for in‐plane strains. As a result, all EXG shell elements developed pass membrane and bending plate patch tests and exhibit a superior performance in the case of distorted coarse mesh configurations. Copyright © 2010 John Wiley & Sons, Ltd.
An extended finite element method applied to levitated droplet problems
Authors: Esser Patrick , Grande Jörg , Reusken Arnold
Published: May 2010

We consider a standard model for incompressible two‐phase flows in which a localized force at the interface describes the effect of surface tension. If a level set method is applied then the approximation of the interface is in general not aligned with the triangulation. This causes severe difficulties w.r.t. the discretization and often results in large spurious velocities. In this paper we reconsider a (modified) extended finite element method (XFEM), which in previous papers has been investigated for relatively simple two‐phase flow model problems, and apply it to a physically realistic levitated droplet problem. The results show that due to the extension of the standard FE space one obtains much better results in particular for large interface tension coefficients. Furthermore, a certain cut‐off technique results in better efficiency without sacrificing accuracy. Copyright © 2010 John Wiley & Sons, Ltd.
A parametric mapping method for curve shape optimization on 3D panel structures
Authors: Zhang Weihong , Wang Dan , Yang Jungang
Published: May 2010

Three‐dimensional (3D) thin‐walled panels belong to a kind of lightweight structures that are widely used in aeronautic and aerospace engineering. This paper deals with the shape optimization of curved contours that exist often on this kind of structures. Compared with conventional 2D and 3D shape optimization problems, the particularity and difficulty existing here are how to define design variables properly so that the curve keeps moving on the specific surface of the curved panel during the design process. A new parametric mapping method (PMM) is therefore proposed in this paper. The originality is to manage shape design variables in the 2D intrinsic coordinate system. It is shown that the geometric limitation is satisfied automatically. Moreover, relevant formulations are developed theoretically for design sensitivity analysis. By means of the parametric mapping from 2D intrinsic coordinate system to Cartesian coordinate system, the mesh velocity field related to the finite element model can be easily computed for any unstructured mesh. Finally, a variety of representative examples are presented to illustrate the method. Copyright © 2010 John Wiley & Sons, Ltd.
Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance
Authors: Wermann Hendrik , Stoop Hans , Gillis Ad JM , Honecker Friedemann , van Gurp Ruud JHLM , Ammerpohl Ole , Richter Julia , Oosterhuis J Wolter , Bokemeyer Carsten , Looijenga Leendert HJ
Published: May 2010

Differences in the global methylation pattern, ie hyper‐ as well as hypo‐methylation, are observed in cancers including germ cell tumours (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n = 103) and GCTs (n = 251) by immunohistochemical staining for 5‐$^{\rm m}$cytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, whereas female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, intratubular germ cell neoplasia unclassified, and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumours, and choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam‐2 before and after demethylation using 5‐azacytidine. Exposure to 5‐azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell‐specific marker VASA, showed increased expression. Following treatment with 5‐azacytidine, TCam‐2 cells were analysed using a high‐throughput methylation screen for changes in the methylation sites of 14 000 genes. Among the genes revealing changes, interesting targets were identified: ie demethylation of KLF11, a putative tumour suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Is there an association between bicuspid aortic valve and neuroblastoma?
Authors: Stefanski Heather , Wedel Lauren , Haller Courtney , Pierpont Mary Ella , Perkins Joanna L.
Published: May 2010

An association has been reported between neuroblastoma and congenital heart disease, frequently bicuspid aortic valve [Holzer and Franklin. Arch Dis Child 2002;87:61–64; George et al. J Pediatr 2004;144:444–448; Friedman et al. Pediatr Cardiol 1998;19:480–481; Monte et al. Am J Pediatr Hematol Oncol 1985;7:109–116]. To evaluate this in a large patient group with neuroblastoma, we examined echocardiograms of patients with neuroblastoma from 1987 to January 2007 to determine if there was a higher incidence of bicuspid aortic valves compared to the general population without neuroblastoma. We found that only 0.7% of neuroblastoma patients had the congenital heart defect of bicuspid aortic valves compared with 1–2% in the general population [Braverman et al. Curr Prob Cardiol 2005;30:470–522]. Our data show that neuroblastoma is not associated with bicuspid aortic valves. Pediatr Blood Cancer. 2010;55:359–360. © 2010 Wiley–Liss, Inc.
T‐cell acute lymphoblastic leukemia in association with Börjeson–Forssman–Lehmann syndrome due to a mutation in PHF6
Authors: Chao Mwe Mwe , Todd Matthew A. , Kontny Udo , Neas Katherine , Sullivan Michael J. , Hunter Alasdair G. , Picketts David J. , Kratz Christian P.
Published: May 2010

Börjeson–Forssman–Lehmann syndrome (BFLS) is a rare X‐linked mental retardation syndrome that is caused by germline mutations in PHF6. We describe a 9‐year‐old male with BFLS, who developed T‐cell acute lymphoblastic leukemia (T‐ALL). The PHF6 gene is located on the X chromosome and encodes a protein with two PHD‐type zinc finger domains and four nuclear localization sequences. Previously, overexpression of Phf6 was observed in murine T‐cell lymphomas. Our observation indicates that BFLS may represent a cancer predisposition syndrome and that mutations of PHF6 contribute to T‐ALL. Pediatr Blood Cancer. 2010;55:722–724. © 2010 Wiley‐Liss, Inc.
Psychological support and care for young people with diabetes in the ‘transition’ period
Authors: Trigwell P , Jawad S
Published: May 2010

The aim of this survey was to determine the availability of psychological support and care for young people with diabetes in secondary care services in the Yorkshire and Humber NHS Region during the transition period (i.e. ages 16–25 years).

The survey was developed in line with both National Institute for Health and Clinical Excellence (NICE) guidance and National Service Framework (NSF) standards specific to children and young people with diabetes. It was distributed to the diabetes services in all 20 centres within the Yorkshire and Humber NHS Region.

The response rate for this survey was 100%. All centres were aware that children and young people with type 1 diabetes may develop anxiety and/or depression, and all (100%) or virtually all (95%) of the teams in the 20 centres agreed with the various key requirements stipulated in the relevant NICE guidance and NSF standards. However, many centres lacked key service elements, or indeed any plans to introduce them.

The findings of this study are of national significance given the nature and size of the region studied and the likelihood that the national picture is similar to this. There is a general sense of awareness among diabetes services and teams regarding the need for psychological support and care for young people with diabetes in the transition period. Despite this, multiple gaps exist in services in relation to the already existing requirements and standards. The implications, including those for service commissioners, are discussed. Copyright © 2010 John Wiley & Sons.
British Association of Retinal Screeners (BARS): survey of workload in UK diabetic retinopathy screening programmes
Authors: Shotliff K , Duncan G , Dewhirst R , Dixon L , Ellingford A , Greenwood R , Mansell J , Mitchell P , Moss G
Published: May 2010

The aim of this survey was to determine the number of patients being screened per session in UK diabetic retinal screening programmes and the number of patients images being graded in stand alone grading sessions.

A questionnaire was sent to all members of the British Association of Retinal Screeners asking for information about diabetic retinal screening schemes in which they were involved.

Sixty‐eight (31%) replied and suggested that an average of 14.4 patients were being screened per session on a fixed site programme, and an average of 15.7 per session with a mobile service. A standard morning session was, on average, 3 hours and 23 minutes long on a fixed site and 3 hours and 14 minutes on a mobile site. A standard afternoon session was, on average, 3 hours and 5 minutes long on a fixed site and 2 hours and 44 minutes long on a mobile site. Those undertaking grading as a stand alone activity screened an average of 39.3 patients per session (ranging from 20–75 patients per session).

While the lengths of morning and afternoon screening sessions were relatively consistent there was more variability in the number of patients whom a stand alone grader would typically grade per session. We believe this range of activity reinforces the importance of a good quality assurance programme to maintain the consistency of the service offered. Copyright © 2010 John Wiley & Sons.