bluuebunny/crossref_metadata_2025 huggingface dataset:
Bisphosphonates and pathologic complete response to taxane‐ and anthracycline‐based neoadjuvant chemotherapy in patients with breast cancer
Authors: Chavez‐MacGregor Mariana , Brown Erika , Lei Xiudong , Litton Jennifer , Meric‐Bernstram Funda , Mettendorf Elizabeth , Hernandez Leonel , Valero Vicente , Hortobagyi Gabriel N. , Gonzalez‐Angulo Ana Maria
Published: May 2011

BACKGROUND:

Several studies have suggested that bisphosphonates have an antitumor effect. In the current study, the authors sought to evaluate whether the use of bisphosphonates increased the rate of pathological complete response (pCR) in patients with breast cancer.

METHODS:

The authors identified 1449 patients with breast cancer who were receiving taxane‐ and anthracycline‐based neoadjuvant chemotherapy between 1995 and 2007 at The University of Texas MD Anderson Cancer Center. Patients who received bisphosphonates for osteopenia or osteoporosis while receiving chemotherapy were also identified. The primary outcome was the percentage of patients achieving a pCR. Groups were compared using the chi‐square test. A multivariable logistic regression model was fit to examine the relation between the use of bisphosphonates and pCR. An exploratory survival analysis using the Kaplan‐Meier method was performed; groups were compared using the log‐rank test.

RESULTS:

Of the 1449 patients included, 39 (2.7%) received bisphosphonates. Those receiving bisphosphonates were older (P < .001) and less likely to be obese (P = .04). The pCR rate was 25.4% in the bisphosphonate group and 16% in the nonbisphosphonate group (P = .11). In the multivariable model, patients treated with bisphosphonates tended to have higher rates of pCR (odds ratio, 2.18; 95% confidence interval, 0.90‐5.24); however, the difference was not found to be statistically significant. With a median follow‐up of 55 months (range, 3 months‐145 months), no differences in disease recurrence or survival were observed.

CONCLUSIONS:

The use of bisphosphonates at the time of neoadjuvant chemotherapy was not found to be associated with a statistically significant increase in the rates of pCR. The observed estimates suggest a positive effect; however, the small percentage of patients receiving bisphosphonates likely affected the power to detect a statistically significant difference. Cancer 2011;. © 2011 American Cancer Society.
Immersed boundary model of aortic heart valve dynamics with physiological driving and loading conditions
Authors: Griffith Boyce E.
Published: May 2011

The immersed boundary (IB) method is a mathematical and numerical framework for problems of fluid–structure interaction, treating the particular case in which an elastic structure is immersed in a viscous incompressible fluid. The IB approach to such problems is to describe the elasticity of the immersed structure in Lagrangian form, and to describe the momentum, viscosity, and incompressibility of the coupled fluid–structure system in Eulerian form. Interaction between Lagrangian and Eulerian variables is mediated by integral equations with Dirac delta function kernels. The IB method provides a unified formulation for fluid–structure interaction models involving both thin elastic boundaries and also thick viscoelastic bodies. In this work, we describe the application of an adaptive, staggered‐grid version of the IB method to the three‐dimensional simulation of the fluid dynamics of the aortic heart valve. Our model describes the thin leaflets of the aortic valve as immersed elastic boundaries, and describes the wall of the aortic root as a thick, semi‐rigid elastic structure. A physiological left‐ventricular pressure waveform is used to drive flow through the model valve, and dynamic pressure loading conditions are provided by a reduced (zero‐dimensional) circulation model that has been fit to clinical data. We use this model and method to simulate aortic valve dynamics over multiple cardiac cycles. The model is shown to approach rapidly a periodic steady state in which physiological cardiac output is obtained at physiological pressures. These realistic flow rates are not specified in the model, however. Instead, they emerge from the fluid–structure interaction simulation. Copyright © 2011 John Wiley & Sons, Ltd.
Cell adhesion molecule cadherin‐6 function in zebrafish cranial and lateral line ganglia development
Authors: Liu Q. , Dalman M.R. , Sarmah S. , Chen S. , Chen Y. , Hurlbut A.K. , Spencer M.A. , Pancoe L. , Marrs J.A.
Published: May 2011

Cadherins regulate the vertebrate nervous system development. We previously showed that cadherin‐6 message (cdh6) was strongly expressed in the majority of the embryonic zebrafish cranial and lateral line ganglia during their development. Here, we present evidence that cdh6 has specific functions during cranial and lateral line ganglia and nerve development. We analyzed the consequences of cdh6 loss‐of‐function on cranial ganglion and nerve differentiation in zebrafish embryos. Embryos injected with zebrafish cdh6 specific antisense morpholino oligonucleotides (MOs, which suppress gene expression during development; cdh6 morphant embryos) displayed a specific phenotype, including (i) altered shape and reduced development of a subset of the cranial and lateral line ganglia (e.g., the statoacoustic ganglion and vagal ganglion) and (ii) cranial nerves were abnormally formed. These data illustrate an important role for cdh6 in the formation of cranial ganglia and their nerves. Developmental Dynamics 240:1716–1726, 2011. © 2011 Wiley‐Liss, Inc.
Effects of n‐3 PUFA on insulin resistance after an oral fat load
Authors: Derosa Giuseppe , Cicero Arrigo F.G. , Fogari Elena , D'Angelo Angela , Bonaventura Aldo , Maffioli Pamela
Published: May 2011

The aim of this study was to evaluate the effects of ω‐3 PUFA (n‐3 PUFA) on lipid profile and insulin resistance biomarkers. Patients were assigned to receive placebo or n‐3 PUFA 1 g three times a day, during the meals, for 6 months. We evaluated: body mass index (BMI), body weight, fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA‐IR), blood pressure, lipid profile, resistin (r), retinol binding protein‐4 (RBP‐4), adiponectin (ADN), visfatin, and vaspin. Furthermore patients underwent an oral fat load (OFL) and an euglycemic hyperinsulinemic clamp to evaluate M value, and total glucose requirement (TGR). Triglycerides value obtained with n‐3 PUFA was lower, while HDL‐C, and ADN values were higher compared to placebo. After the OFL, and comparing the OFL performed at the baseline and at the end of the study, there was a decrease of triglycerides (Tg), resistin (r), and RBP‐4 values, and an increase of ADN value with n‐3 PUFA, but not with placebo. We conclude that the treatment with n‐3 PUFA resulted in a greater improvement of lipid profile and ADN compared to placebo in a baseline condition, and an improvement of all insulin resistance parameters after an OFL.

Practical applications: The inverse association between dietary intake of n‐3 PUFA and cardiovascular disease morbidity/mortality was primarily established following the observation that the Greenland Inuits had low mortality from coronary heart disease despite a fat‐rich diet. Our group has already shown that n‐3 PUFA improved the lipid profile and the coagulation, fibrinolytic, and inflammatory parameters compared to placebo. We also observed that highly purified n‐3 PUFA supplementation significantly reduced the blood pressure, pulse pressure, and basal heart rate in hypertriglyceridemic patients with normal‐high blood pressure. The current study showed that treatment with n‐3 PUFA not only improved lipid profile in a baseline situation, but it also improved all insulin resistance parameters in a post‐prandial situation simulated with an OFL. This is another important action of the n‐3 PUFA which can increase their utility in the clinical practice.
Aqueous enzymatic process for oil and protein extraction from Moringa oleifera seed
Authors: Latif Sajid , Anwar Farooq , Hussain Abdullah I. , Shahid Muhammad
Published: May 2011

Five commercial enzyme mixtures were evaluated for simultaneous oil and protein extraction from Moringa seed through enzyme‐assisted aqueous extraction (EAE). Protex 7L was found to be the best enzyme for highest oil (69.4%) extraction and protein (75.4%) recovery in the aqueous phase. The quality parameters of enzyme‐assisted aqueous extracted oil (EAEO), aqueous extracted oil (AEO), and hexane extracted oil (HEO) were compared. Among oils produced by these methods, fatty acids (FAs) profiles, density, refractive index, iodine value, saponification value, and unsaponifiable matter were found to be analogous, whereas significantly (p < 0.05) lower color and free FA contents in the EAEO and AEO than that of HEO were observed. The specific extinctions at 232 and 270 nm, p‐anisidine, and peroxide values of the EAEO and AEO were improved in comparison to HEO. An increase in tocopherol content and antioxidant activity measured by total phenolic content, DPPH radical scavenging capacity, and inhibition of linoleic acid oxidation in the EEO was observed as compared to the AEO and HEO. In general, the quality of the EAEO was improved and a significant amount of protein was simultaneously extracted which can be employed in food/feed applications.
Effect of acyl migration in Lipozyme TL IM‐catalyzed interesterification using a triacylglycerol model system
Authors: Svensson Julia , Adlercreutz Patrick
Published: May 2011

Lipase‐ (Lipozyme TL IM) catalyzed interesterification of triacylglycerols was studied at water activities (aw) from 0.22 to 0.8. The substrates trilaurin (LLL) and 1,3‐palmitin‐2‐olein (POP) were used in equimolar amounts to facilitate separate measurements of the interesterification in the sn‐1,3 positions and changes in the fatty acid (FA) composition in the sn‐2 position. The reaction at aw = 0.35 was the fastest, and that at aw = 0.84 the slowest, due to increased hydrolysis. The interesterification in the sn‐1,3 positions was above 90% after 2 h reaction at aw = 0.22, 0.35, and 0.54, and the main triacylglycerols were LLP, POL, LOL, and PLP. The FA composition in the sn‐2 position was conserved during the first 1–2 h, and the randomization due to acyl migration was complete after 24 h. During the entire reaction, FA present in the sn‐1,3 positions were removed from the triacylglycerols by the enzyme, and a fraction of them was released by hydrolysis. The gradual change in the composition of the free FA thus reflected the randomization of FA within the triacylglycerol molecules. Improved knowledge on the factors affecting the rates of interesterification, hydrolysis, and randomization is required to develop tailor‐made lipid products.

Practical applications: In an ideal 1,3‐specific lipase‐catalyzed interesterification reaction, the FA composition in the sn‐2 position remains constant. In practice, small changes are seen in the FA composition in this position, and under certain conditions a completely randomized FA distribution can be obtained. Randomization is slower than interesterification. Uncontrolled hydrolysis should be avoided because it lowers the TAG yield. By varying the reaction time, different triacylglycerol mixtures can be produced: i.e. products originating from 1,3‐specific interesterification, as well as partially or completely randomized products.
Performance evaluation of a distributed hybrid test framework to reproduce the collapse behavior of a structure
Authors: Wang Tao , Mosqueda Gilberto , Jacobsen Andres , Cortes‐Delgado Maria
Published: May 2011

A hybrid numerical and experimental simulation to collapse was conducted on a one‐half scale moment‐resisting frame building with two experimental substructures at different locations. An extensible hybrid test framework was used that adopts a generalized interface to encapsulate each numerical or tested substructure, through which only boundary displacements and forces are exchanged. Equilibrium and compatibility between substructures are enforced by an iterative quasi‐Newton procedure, while adopting a predictor‐and‐corrector method to avoid loading reversals on physically tested substructures. To overcome difficulties in controlling stiff axial and rotational deformations at the boundaries, the flexible test scheme employs either open‐loop or closed‐loop control at the boundaries: enforcing either compatibility or equilibrium, or both requirements at critical boundaries. The effectiveness of the extensible framework and its capability to simulate structural behavior through collapse is demonstrated by a geographically distributed test that reproduced the collapse behavior of a four‐story, two‐bay, steel moment frame previously tested on an earthquake simulator. A comparison of both experiments highlights the viability of the hybrid test as an effective tool for the performance evaluation of structural systems from the onset of damage through collapse. Copyright © 2011 John Wiley & Sons, Ltd.
Large eddy simulation in generalized curvilinear coordinates using conventional approach: Theory and validation
Authors: Panjwani Balram , Ertesvåg Ivar S. , Gruber Andrea , Rian Kjell Erik
Published: May 2011

Large eddy simulation (LES) methodology in curvilinear coordinates is presented in this study, where filtering is performed prior to the transformation in contrast to the alternate approach proposed by Jordan [J. Comput. Phys. 1999; 148:322–340], where filtering is done after the transformation. The main objective of the present study is to elaborate on the problems mentioned by Jordan with the conventional approach, and its consequences for the overall accuracy. The paper also provides remedies to the problems associated with the conventional approach. The present method treats the Leonard term in physical space rather than in computational space. Some practical difficulties associated with the alternate approach are also considered. Main advantages with the present conventional approach are: first an existing Reynolds averaged Navier–Stokes code can easily be extended for LES and second a wide range of existing advanced subgrid stress model can be used without any modifications. Filtering in physical space introduces a commutation error between filtering and differentiation due to non‐uniform meshes. The commutation filters in generalized coordinates are presented. LESs of four standard test cases are carried out to validate the present methodology. The four standard test cases are: (i) a lid‐driven cavity at Reynolds number (Re) of 12 000, (ii) a pipe flow at a friction Reynolds number Reτ of 360, (iii) a backward facing step at Re = 5100, and (iv) an axisymmetric confined dump combustor at Re = 11000. The results are validated against the reference data (direct numerical simulation or experiments). The mean velocity profiles and the turbulence intensities compared satisfactorily with the reference data. Copyright © 2011 John Wiley & Sons, Ltd.
A novel WWTR1‐CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites
Authors: Errani Costantino , Zhang Lei , Sung Yun Shao , Hajdu Mihai , Singer Samuel , Maki Robert G. , Healey John H. , Antonescu Cristina R.
Published: May 2011

The classification of epithelioid vascular tumors remains challenging, as there is considerable morphological overlap between tumor subtypes, across the spectrum from benign to malignant categories. A t(1;3)(p36.3;q25) translocation was reported in two cases of epithelioid hemangioendothelioma (EHE), however, no follow‐up studies have been performed to identify the gene fusion or to assess its prevalence in a larger cohort of patients. We undertook a systematic molecular analysis of 17 EHE, characterized by classic morphological and immunophenotypic features, from various anatomical locations and with different malignant potential. For comparison, we analyzed 13 epithelioid hemangiomas, five epithelioid angiosarcomas, and four epithelioid sarcoma‐like EHE. A fluorescence in situ hybridization (FISH) positional cloning strategy, spanning the cytogenetically defined regions on chromosomes 1p36.3 and 3q25, confirmed rearrangements in two candidate genes from these loci in all EHE cases tested. None of the other benign or malignant epithelioid vascular tumors examined demonstrated these abnormalities. Subsequent reverse transcription‐polymerase chain reaction (RT‐PCR) confirmed in three EHE the WWTR1‐CAMTA1 fusion product. CAMTA1 and WWTR1 have been previously shown to play important roles in oncogenesis. Our results demonstrate the presence of a WWTR1‐CAMTA1 fusion in all EHE tested from bone, soft tissue, and visceral location (liver, lung) in keeping with a unique and specific pathological entity. Thus, FISH or RT‐PCR analysis for the presence of WWTR1‐CAMTA1 fusion may serve as a useful molecular diagnostic tool in challenging diagnoses. © 2011 Wiley‐Liss, Inc.
Relative 8q gain predicts disease‐specific survival irrespective of the TMPRSS2‐ERG fusion status in diagnostic biopsies of prostate cancer
Authors: Barros‐Silva João D. , Ribeiro Franclim R. , Rodrigues Ângelo , Cruz Ricardo , Martins Ana T. , Jerónimo Carmen , Henrique Rui , Teixeira Manuel R.
Published: May 2011

Screening tools have greatly improved prostate cancer (PCa) detection, but the disease course is heterogeneous, and standard clinicopathological parameters do not fully discriminate aggressive from indolent tumors. To evaluate the prognostic value of the TMPRSS2‐ERG fusion gene combined with chromosome arm 8q relative gain in diagnostic biopsies of PCa, we studied a consecutive series of 200 diagnostic needle biopsies from patients with 10‐year disease‐specific survival data. TMPRSS2‐ERG fusion gene status and relative 8q gain were assessed by fluorescent in situ hybridization in whole formalin fixed paraffin‐embedded biopsies. The TMPRSS2‐ERG fusion gene was detected in 43.5% of PCa and was associated with lower Gleason score (P = 0.045), whereas relative 8q gain was present in 48% of PCa and was associated in high‐Gleason score (P < 0.001). ERG rearrangement alone was not associated with clinical outcome, whereas relative 8q gain predicted worse disease‐specific survival in PCa patients both with and without the TMPRSS2‐ERG fusion gene (P < 0.001), independently of Gleason score, clinical stage, and treatment modality. We conclude that relative 8q gain in diagnostic needle biopsies is a poor prognostic factor independent of the TMPRSS2‐ERG fusion gene status and of standard clinicopathological parameters. © 2011 Wiley‐Liss, Inc.
Identification of genetic disparity between primary and metastatic melanoma in human patients
Authors: Swoboda Alexander , Rasin‐Streden Doris , Schanab Oliver , Okamoto Ichiro , Pehamberger Hubert , Petzelbauer Peter , Mikula Mario
Published: May 2011

It is commonly accepted that cancer cell progression is accompanied by accumulation of genetic changes. Here we searched for copy number variations in melanoma and asked whether homozygous losses always cumulate during tumor cell progression. Therefore we investigated either melanoma cell lines or tissue derived from the primary lesion and from the lymph node metastasis of the same individual patient. In vitro studies of melanoma cell lines revealed high migratory and anchorage independent growth of metastasis‐derived cells. Surprisingly, whole genome DNA analysis of a primum‐derived cell line revealed a total of 10 homozygous losses, whereas the matched metastasis‐derived cell line only shared five of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis‐derived cell line and no growth of primum‐derived cells. Additionally, we screened matched pairs of patient‐derived melanoma primum and metastasis samples and we could also identify a case with homozygous deletions exclusively present in the primary lesion. Therefore, we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. We propose that for mutation‐targeted therapy genotyping should be performed not only from primary, but also from metastatic melanoma. © 2011 Wiley‐Liss, Inc.
Chromosomal copy number alterations are associated with tumor response to chemoradiation in locally advanced rectal cancer
Authors: Chen Zhenbin , Liu Zheng , Li Wenyan , Qu Kun , Deng Xutao , Varma Madhulika G. , Fichera Alessandro , Pigazzi Alessio , Garcia‐Aguilar Julio
Published: May 2011

Rectal cancer response to chemoradiation (CRT) varies from no response to a pathologic complete response (pCR). Identifying predictive biomarkers of response would therefore be useful. We assessed whether chromosomal copy number alterations (CNAs) can assist in predicting pCR. Pretreatment tumor biopsies and paired normal surgical tissues from the proximal resection margin were collected from 95 rectal cancer patients treated with preoperative CRT and total mesorectal excision in a prospective Phase II study. Tumor and control DNA were extracted, and oligonucleotide array‐based comparative genomic hybridization (aCGH) was used to identify CNAs, which were correlated with pCR. Ingenuity pathway analysis (IPA) was then used to identify functionally relevant genes in aberrant regions. Finally, a predictive model for pCR was built using support vector machine (SVM), and leave‐one‐out cross validation assessed the accuracy of aCGH. Chromosomal regions most commonly affected by gains were 20q11.21‐q13.33, 13q11.32‐23, 7p22.3‐p22.2, and 8q23.3‐q24.3, and losses were present at 18q11.32‐q23, 17p13.3‐q11.1, 10q23.1, and 4q32.1‐q32.3. The 25 (26%) patients who achieved a pCR had significantly fewer high copy gains overall than non‐pCR patients (P = 0.01). Loss of chromosomal region 15q11.1‐q26.3 was significantly associated with non‐pCR (P < 0.00002; Q‐bound < 0.0391), while loss of 12p13.31 was significantly associated with pCR (P < 0.0003; Q‐bound < 0.097). IPA identified eight genes in the imbalanced chromosomal regions that associated with tumor response. SVM identified 58 probes that predict pCR with 76% sensitivity, 97% specificity, and positive and negative predictive values of 91% and 92%. Our data indicate that chromosomal CNAs can help identify rectal cancer patients more likely to develop a pCR to CRT. © 2011 Wiley‐Liss,Inc.
The evolutionary origins of glia
Authors: Hartline Daniel K.
Published: May 2011

The evolutionary origins of glia are lost in time, as soft tissues rarely leave behind fossil footprints, and any molecular footprints they might have been left we have yet to decipher. Nevertheless, because of the growing realization of the importance glia plays in the development and functioning of the nervous system, lessons we can draw about commonalities among different taxa (including vertebrates) brought about either from a common origin, or from common adaptational pressures, shed light on the roles glia play in all nervous systems. The Acoelomorpha, primitive interstitial flatworms with very simple cellular organization and currently at the base of the bilaterian phylogeny, possess glia‐like cells. If they indeed represent the ancestors of all other Bilateria, then it is possible that all glias derive from a common ancestor. However, basal taxa lacking convincing glia are found in most major phyletic lines: urochordates, hemichordates, bryozoans, rotifers, and basal platyhelminths. With deep phylogenies currently in flux, it is equally possible that glia in several lines had different origins. If developmental patterns are any indication, glia evolved from ectodermal cells, possibly from a mobile lineage, and even possibly independently in different regions of the body. As to what functions might have brought about the evolution of glia, by‐product removal, structural support, phagocytic needs, developmental programming, and circuit modulation may be the more likely. Explaining possible cases of glial loss is more difficult, as once evolved, glia appears to keep inventing new functions, giving it continued value even after the original generative need becomes obsolete. Among all the uncertainties regarding the origin of glia, one thing is certain: that our ideas about those origins will change with every rearrangement in deep phylogeny and with continued advances in invertebrate molecular and developmental areas. © 2011 Wiley‐Liss, Inc.
Endonasal transpterygoid approach to the infratemporal fossa: Correlation of endoscopic and multiplanar CT anatomy
Authors: Mousa Sadr Hosseini Seid , Razfar Ali , Carrau Ricardo L. , Prevedello Daniel M. , Fernandez–Miranda Juan , Zanation Adam , Kassam Amin B.
Published: May 2011

Background

The infratemporal fossa anatomy, from an endoscopic standpoint, is poorly understood. Our purpose was to design an anatomic model that illustrates the anatomy of the infratemporal fossa from the endoscopic standpoint and serves as a training model for surgeons interested in pursuing this endeavor.

Methods

Red and blue silicone dyes were respectively injected into the great vessels of the neck. Digital data acquired from a high resolution CT scan was imported to a navigational system. An endoscopic endonasal dissection of the infratemporal fossa was completed under conditions that mimicked our operating suite.

Results

A detailed anatomic dissection of the infratemporal fossa was correlated to the image guidance (navigation) system. This provided a surgical map highlighting critical neurovascular structures and illustrating the potential surgical corridors.

Conclusion

A thorough understanding of the anatomy of infratemporal fossa from the endoscopic perspective allows the surgeon to plan an adequate corridor. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Modulation of the opioid growth factor ([Met5]‐enkephalin)–opioid growth factor receptor axis: Novel therapies for squamous cell carcinoma of the head and neck
Authors: McLaughlin Patricia J. , Stucki Jaimon K. , Zagon Ian S.
Published: May 2011

Background

The opioid growth factor (OGF)–OGF receptor (OGFr) axis is a constitutively expressed biologic pathway regulating cell proliferation of squamous cell carcinoma of the head and neck (SCCHN). This study investigated modulation of the OGF–OGFr system by (1) exogenous OGF, (2) upregulation of OGFr using imiquimod, or (3) intermittent opioid receptor blockade with a low dose of naltrexone on progression of established SCCHN.

Methods

Nude mice with visible human SCCHN SCC‐1 tumors received (1) OGF or low‐dose naltrexone either 1, 3, or 7 times/week or (2) imiquimod 1 or 3 times/week. Tumor growth and DNA synthesis were monitored.

Results

OGF and low‐dose naltrexone increased the latency from visible to measurable tumors up to 1.6‐fold. OGF, low‐dose naltrexone, and imiquimod treatment markedly reduced tumor volume and weight, and decreased DNA synthesis in tumors.

Conclusions

Modulation of the native OGF–OGFr regulatory network in SCCHN represents a novel nontoxic and highly efficacious approach for treatment of SCCHN. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Craniopharyngioma: A pathologic, clinical, and surgical review
Authors: Fernandez‐Miranda Juan C. , Gardner Paul A. , Snyderman Carl H. , Devaney Kenneth O. , Strojan Primož , Suárez Carlos , Genden Eric M. , Rinaldo Alessandra , Ferlito Alfio
Published: May 2011

Craniopharyngioma is a rare and mostly benign epithelial tumor of the sellar and suprasellar region. Two principal patterns of craniopharyngioma are recognized: papillary and adamantinomatous. Papillary craniopharyngiomas are encountered in adults and may lack the cystic spaces filled with “motor oil” as well as the palisading peripheral rows of epithelial cells, keratinization, or calcification typical of pediatric adamantinomatous craniopharyngioma. Secondary to their anatomic location, craniopharyngiomas may present with endocrinologic dysfunction and visual disturbances. Differential diagnosis includes Rathke's cleft cyst, pituitary adenoma, dermoid/epidermoid cysts, and other rare sellar/suprasellar lesions as pituicytomas. Many controversies exist concerning the preferred surgical approach for these tumors. Endoscopic endonasal surgery is no longer reserved only for sellar or small cystic suprasellar lesions. Prechiasmatic/preinfundibular lesions are effectively removed using an endonasal transtuberculum/transplanum approach; subchiasmatic/transinfundibular tumors require the addition of a transellar approach with inferior pituitary transposition; and retrochiasmatic/retroinfundibular lesions are better accessed performing an endonasal superior pituitary transposition. Compared with well‐established trancranial approaches (pterional, subfrontal, presigmoid), endoscopic endonasal surgery combines the virtues of the caudocranial and midline approaches, allowing for appropriate infrachiasmatic exposure without the need for manipulation of surrounding neurovascular structures to access the tumor. This anatomic advantage, combined with high‐definition wide‐angle visualization, exquisite endonasal microsurgical techniques, and devoted instrumentation facilitates a high rate of endocrine function preservation and visual improvement, while concurrently achieving comparable resections. Endoscopic skull base reconstruction with the vascularized nasoseptal flap has dramatically reduced the incidence of cerebrospinal fluid leak, consolidating endoscopic endonasal surgery as an effective and safe alternative for the treatment of these challenging tumors. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
The hippocampus is involved in mental navigation for a recently learned, but not a highly familiar environment: A longitudinal fMRI study
Authors: Hirshhorn Marnie , Grady Cheryl , Rosenbaum R.Shayna , Winocur Gordon , Moscovitch Morris
Published: May 2011

Functional magnetic resonance imaging (MRI) was used to investigate the hypothesis that memory for a large‐scale environment is initially dependent on the hippocampus but is later supported by extra‐hippocampal structures (e.g., precuneus, posterior parahippocampal cortex, and lingual gyrus) once the environment is well‐learned. Participants were scanned during mental navigation tasks initially when they were newly arrived to the city of Toronto, and later after having lived and navigated within the city for 1 yr. In the first session, activation was observed in the right hippocampus, left precuneus, and postcentral gyrus. The second session revealed activation in the caudate and lateral temporal cortex, but not in the right hippocampus; additional activation was instead observed in the posterior parahippocampal cortex, lingual gyrus, and precuneus. These findings suggest that the right hippocampus is required for the acquisition of new spatial information but is not needed to represent this information when the environment is highly familiar. © 2011 Wiley Periodicals, Inc.
Impact of Chaoborus flavicans ‐Predation on the Zooplankton in a Mesotrophic Lake – a Three Year Study
Authors: Jäger Ines S. , Hölker Franz , Flöder Sabine , Walz Norbert
Published: May 2011

The predatory impact of Chaoborus flavicans on zooplankton, especially on daphniids, is often regarded as a crucial factor in the propagation or repeal of top‐down effects in lakes. Therefore consumption rates and prey selectivity of C. flavicans were determined in mesotrophic Lake Großer Vätersee, where cladocerans were the dominant zooplankton prey and the predatory impact of fish towards C. flavicans and cladocerans was low. Two generations of the main predatory instar IV of C. flavicans appeared in the pelagial, the first in autumn and the second in spring after having over wintered in the sediment. In discrepancy to the abundances, only the autumn generation showed high peaks of consumption. C. flavicans fed preferentially on medium‐sized cladocerans, but mostly disregarded daphniids and rotifers. Copepods were only selected when cladocerans were not present. The highest losses due to Chaoborus predation were found in Bosmina longirostris, Bosmina coregoni and Chydorus sphaericus. There was no evidence that the predatory impact of C. flavicans on daphniids substantially influenced lower trophic levels. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Contrasting Zooplankton Assemblages in Two Oxbow Lakes with Low Transparencies and Narrow Emergent Macrophyte Belts (Krapina River, Croatia)
Authors: Špoljar Maria , Dražina Tvrtko , Habdija Ivan , Meseljević Matija , Grčić Zlatko
Published: May 2011

The aim of this study was to examine the combined effect of water transparency and narrow macrophyte belts on zooplankton assemblages in two oxbow lakes (Krapina River, Croatia). Samples were collected in open water and among helophytes in the littoral zone from April until September 2008. Rotifers were the most abundant group of zooplankton in both lakes, and dominated in the Krapina oxbow lake 1 (KO1). Lake KO1 had significantly lower transparency, lower percentage macrophyte cover and higher chlorophyll a concentration than Krapina oxbow lake 2 (KO2). In lake KO1, variation in the horizontal distribution of cladocerans and rotifers in terms of their abundance seemed to be determined by competition between Bosmina longirostris and Keratella cochlearis, initiated by oscillation in transparency and detritus availability. In lake KO2, with higher transparency and higher percentage macrophyte cover, the abundance of small‐ and large‐bodied cladocerans increased in the littoral zone simultaneously with higher transparency, suggesting fish predation. Results of this study indicated that small differences in transparencies between the two lakes caused significant differences in horizontal distribution of the zooplankton assemblage. Even narrow helophyte belts offered a refuge to zooplankton, although lower transparencies reduced the effectiveness of macrophytes as a refuge from predators. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Distribution of Herbaceous Species in the Soil Seed Bank of a Flood Seasonality Area, Northern Pantanal, Brazil
Authors: Alves Pagotto Mariana , de Moraes Lima Silveira Roberto , Nunes da Cunha Cátia , Fantin‐Cruz Ibraim
Published: May 2011

To identify factors affecting the spatial distribution of soil seed banks of herbaceous species in the Pantanal floodplain, Brazil, the aims of this study were: to characterize the seed bank in terms of the abundance, richness and composition of germinated seeds; to relate these characteristics to flood duration, elevation, chemical and physical properties of the soil and to examine the seed bank’s spatial pattern. Soil samples were collected at 14 points and were then placed in a greenhouse to allow germination to occur. Each sample point had the flood level monitored, the elevation measured and the soil properties identified. A total of 1710 seedlings from 26 species were recorded, of which Echinodorus tenelus was the most abundant (24.9%). Cyperaceae and Poaceae were the richest floristic families (5 species each), with Alismataceae the most represented in terms of number of individuals (36% of the total). Duration of flooding plays an important role in determining Pantanal soil seed banks. The flood pulse influences the abundance (r = 0.79; P = 0.006; partial), richness (r = 0.61; P = 0.02; partial) and composition of the soil seed bank (Pillai trace = 0.552; P = 0.027), carrying the seeds to areas where the duration of flood is longer. Except for aluminium, the soil characteristics expressed by the first principal component of PCA exert indirect positive effects on the seed bank. This is because this component was correlated with the duration of inundation (r = 0.76). Elevation and the toxic effect of aluminium do not vary sufficiently to be able to influence seed bank characteristics. The correlograms show that soil seed banks have no discernible spatial pattern, even though most species are dispersed hydrochorically. This suggests that, at the scale of the study, the tendency for flooding to cause homogeneous dispersion has no influence on seed‐bank spatial structure, because of the complexity of flood‐plain geomorphology. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Phylogenetic, Spatial, and Species‐Trait Patterns across Environmental Gradients: the Case of Hydropsyche (Trichoptera) along the Loire River
Authors: Statzner Bernhard , Dolédec Sylvain
Published: May 2011

When Illies published his concept on the longitudinal zonation of lotic invertebrates five decades ago (Illies, J., 1961: Internat. Rev. ges. Hydrobiol. 46: 205–213), he defined a research topic that currently interests many ecologists because he linked speciation and phylogeny with spatial distribution and trait adaptation to environmental conditions prevailing along rivers. We tested these ideas analyzing nine species of the caddisfly genus Hydropsyche from the Loire River (France). A morphology‐based phylogeny illustrated that the oldest of our species occurred in the headwater and that specific phylogenetic distances from the root location in the tree were significantly related to the specific longitudinal occurrences in the Loire. Furthermore, traits such as oxygen consumption, optimal velocity for filter‐net‐building, and larval size were significantly related to the specific phylogenetic distances, indicating meaningful, gradual adaptations to environmental gradients prevailing along European rivers (particularly in water temperature, near‐bottom flow, sediment porosity). Thus, joining phylogeny, spatial distribution, and species traits provided insights into a central topic of contemporary ecology, the spatial patterns of speciation, taxonomic community structure (species distributions), and niche adaptation (traits). (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
DXA measurements in rett syndrome reveal small bones with low bone mass
Authors: Roende Gitte , Ravn Kirstine , Fuglsang Kathrine , Andersen Henrik , Bieber Nielsen Jytte , Brøndum-Nielsen Karen , Jensen Jens-Erik Beck
Published: May 2011

Low bone mass is reported in growth-retarded patients harboring mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene causing Rett syndrome (RTT). We present the first study addressing both bone mineral density (BMD) and bone size in RTT. Our object was to determine whether patients with RTT do have low BMD when correcting for smaller bones by examination with dual-energy X-ray absorptiometry (DXA). We compared areal BMD (aBMDspine and aBMDtotal hip) and volumetric bone mineral apparent density (vBMADspine and vBMADneck) in 61 patients and 122 matched healthy controls. Further, spine and hip aBMD and vBMAD of patients were associated with clinical risk factors of low BMD, low-energy fractures, MECP2 mutation groups, and X chromosome inactivation (XCI). Patients with RTT had reduced bone size on the order of 10% and showed lower values of spine and hip aBMD and vBMAD (p < .001) adjusted for age, pubertal status, and body mass index (BMI). aBMDspine, vBMADspine, and aBMDtotal hip were associated with low-energy fractures (p < .05). Walking was significantly associated to aBMDtotal hip and vBMADneck adjusted for age and body mass index (BMI). Further, vBMADneck was significantly associated to a diagnosis of epilepsy, antiepileptic treatment, and MECP2 mutation group, but none of the associations with vBMADneck remained clinically significant in a multiple adjusted model including age and BMI. Neither aBMDspine, vBMADspine, nor aBMDtotal hip were significantly associated with epilepsy, antiepileptic treatment, MECP2 mutation group, XCI, or vitamin D status. Low bone mass and small bones are evident in RTT, indicating an apparent low-bone-formation phenotype. © 2011 American Society for Bone and Mineral Research
Adenosine receptor subtype expression and activation influence the differentiation of mesenchymal stem cells to osteoblasts and adipocytes
Authors: Gharibi Borzo , Abraham Anju A , Ham Jack , Evans Bronwen AJ
Published: May 2011

Osteoblasts and adipocytes differentiate from a common precursor cell, the mesenchymal stem cell (MSC). Adenosine is known to signal via four adenosine receptor subtypes, and significantly, recent findings indicate that these may play a role in MSC differentiation. We therefore investigated adenosine receptor expression and activation during the differentiation of MSCs to osteoblasts and adipocytes. The A2BR was dominant in MSCs, and its expression and activity were transiently upregulated at early stages of osteoblastic differentiation. Both activation and overexpression of A2BR induced the expression of osteoblast-related genes [Runx2 and alkaline phosphatase (ALP)], as well as ALP activity, and stimulation increased osteoblast mineralization. The expression of A2AR was upregulated during later stages of osteoblastic differentiation, when its activation stimulated ALP activity. Differentiation of MSCs to adipocytes was accompanied by significant increases in A1R and A2AR expression, and their activation was associated with increased adipogenesis. Enhanced A2AR expression was sufficient to promote expression of adipocyte-related genes (PPARγ and C/EBPα), and its activation resulted in increased adipocytic differentiation and lipid accumulation. In contrast, the A1R was involved mainly in lipogenic activity of adipocytes rather than in their differentiation. These results show that adenosine receptors are differentially expressed and involved in lineage-specific differentiation of MSCs. We conclude, therefore, that fruitful strategies for treating diseases associated with an imbalance in the differentiation and function of these lineages should include targeting adenosine receptor signal pathways. Specifically, these research avenues will be useful in preventing or treating conditions with insufficient bone or excessive adipocyte formation. © 2011 American Society for Bone and Mineral Research
Connexin43 deficiency reduces the sensitivity of cortical bone to the effects of muscle paralysis
Authors: Grimston Susan K , Goldberg Daniel B , Watkins Marcus , Brodt Michael D , Silva Matthew J , Civitelli Roberto
Published: May 2011

We have shown previously that the effect of mechanical loading on bone depends in part on connexin43 (Cx43). To determine whether Cx43 is also involved in the effect of mechanical unloading, we have used botulinum toxin A (BtxA) to induce reversible muscle paralysis in mice with a conditional deletion of the Cx43 gene in osteoblasts and osteocytes (cKO). BtxA injection in hind limb muscles of wild-type (WT) mice resulted in significant muscle atrophy and rapid loss of trabecular bone. Bone loss reached a nadir of about 40% at 3 weeks after injection, followed by a slow recovery. A similar degree of trabecular bone loss was observed in cKO mice. By contrast, BtxA injection in WT mice significantly increased marrow area and endocortical osteoclast number and decreased cortical thickness and bone strength. These changes did not occur in cKO mice, whose marrow area is larger, osteoclast number higher, and cortical thickness and bone strength lower relative to WT mice in basal conditions. Changes in cortical structure occurring in WT mice had not recovered 19 weeks after BtxA injection despite correction of the early osteoclast activation and a modest increase in periosteal bone formation. Thus BtxA-induced muscle paralysis leads to rapid loss of trabecular bone and to changes in structural and biomechanical properties of cortical bone, neither of which are fully reversed after 19 weeks. Osteoblast/osteocyte Cx43 is involved in the adaptive responses to skeletal unloading selectively in the cortical bone via modulation of osteoclastogenesis on the endocortical surface. © 2011 American Society for Bone and Mineral Research
Histone deacetylase inhibitor MS-275 stimulates bone formation in part by enhancing Dhx36-mediated TNAP transcription
Authors: Kim Ha-Neui , Lee Jong-Ho , Bae Suk-Chul , Ryoo Hyun-Mo , Kim Hong-Hee , Ha Hyunil , Lee Zang Hee
Published: May 2011

Histone deacetylases (HDACs) deacetylate both histones and nonhistone proteins and play a key role in the regulation of physiologic and aberrant gene expression. Inhibition of HDACs has emerged as a promising therapeutic target for cancer and neurologic diseases. In this study we investigated the osteogenic effect and mechanism of action of MS-275, a class I HDAC inhibitor with preference for HDAC1. Both local and systemic administration of MS-275 stimulated bone regeneration in animal models. MS-275 stimulated mRNA expression and activity of the early osteogenic marker tissue-nonspecific alkaline phosphatase (TNAP) in bone tissue and osteogenic cells. By using a series of TNAP promoter deletion constructs and a DNA affinity precipitation assay, we identified DExH-box helicase Dhx36 as a factor that binds to the MS-275 response element in the TNAP promoter. We also found that Dhx36 binding to the MS-275 response element is crucial for MS-275 induction of TNAP transcription. Dhx36 physically interacted with a subset of HDACs (HDAC1 and -4) whose protein levels were downregulated by MS-275, and forced expression of these HDACs blunted the stimulatory effects of MS-275 by a deacetylase activity–independent mechanism(s). Taken together, the results of our study show that MS-275 induces TNAP transcription by decreasing the interaction of HDAC1/4 with Dhx36, which can at least in part contribute to the bone anabolic effects of MS-275. © 2011 American Society for Bone and Mineral Research
Volumetric bone mineral density and bone structure in childhood chronic kidney disease
Authors: Wetzsteon Rachel J , Kalkwarf Heidi J , Shults Justine , Zemel Babette S , Foster Bethany J , Griffin Lindsay , Strife C Frederic , Foerster Debbie L , Jean-Pierre Darlene K , Leonard Mary B
Published: May 2011

Chronic kidney disease (CKD) is associated with increased fracture risk and skeletal deformities. The impact of CKD on volumetric bone mineral density (vBMD) and cortical dimensions during growth is unknown. Tibia quantitative computed tomographic scans were obtained in 156 children with CKD [69 stages 2 to 3, 51 stages 4 to 5, and 36 stage 5D (dialysis)] and 831 healthy participants aged 5 to 21 years. Sex-, race-, and age- or tibia length–specific Z-scores were generated for trabecular BMD (TrabBMD), cortical BMD (CortBMD), cortical area (CortArea) and endosteal circumference (EndoC). Greater CKD severity was associated with a higher TrabBMD Z-score in younger participants (p < .001) compared with healthy children; this association was attenuated in older participants (interaction p < .001). Mean CortArea Z-score was lower (p < .01) in CKD 4–5 [−0.49, 95% confidence interval (CI) −0.80, −0.18)] and CKD 5D (−0.49, 95% CI −0.83, −0.15) compared with healthy children. Among CKD participants, parathyroid hormone (PTH) levels were positively associated with TrabBMD Z-score (p < .01), and this association was significantly attenuated in older participants (interaction p < .05). Higher levels of PTH and biomarkers of bone formation (bone-specific alkaline phosphatase) and resorption (serum C-terminal telopeptide of type 1 collagen) were associated with lower CortBMD and CortArea Z-scores and greater EndoC Z-score (r = 0.18–0.36, all p ≤ .02). CortBMD Z-score was significantly lower in CKD participants with PTH levels above versus below the upper limit of the Kidney Disease Outcome Quality Initiative (KDOQI) CKD stage-specific target range: −0.46 ± 1.29 versus 0.12 ± 1.14 (p < .01). In summary, childhood CKD and secondary hyperparathyroidism were associated with significant reductions in cortical area and CortBMD and greater TrabBMD in younger children. Future studies are needed to establish the fracture implications of these alterations and to determine if cortical and trabecular abnormalities are reversible. © 2011 American Society for Bone and Mineral Research