bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a method allowing preservation of fresh lymph nodes for flow cytometric immunophenotyping
Authors: Brincat Patricia , Degaetano James , Donaldson Craig
Published: April 2012

Background:

Flow cytometric immunophenotyping (FCI) of lymph nodes (LN) requires fresh unfixed tissue, with analysis being carried out within few hours post surgery. This study evaluated a novel method for fresh LN preservation, in order to allow histomorphology‐based FCI.

Methods:

This study was carried out prospectively on 30 LN with suspected involvement by haematolymphoid neoplasms (HLN). FCI was performed on each fresh and post cryopreserved LN cell suspension. Percentage positivities (PP) and mean fluorescent intensities (MFI) were calculated on both preparations for a combination of T and B‐lymphoid antigens together with viability.

Results:

The cryopreservation method applied in this study did not affect significantly PP and had minor impact on MFI of the tested antigens. Overall, there was minimal decrease in PP and MFI on the cryopreserved cells when compared with fresh cells, for most antigens with only a mild increase in apoptotic cells. However, these changes were not diagnostically significant, since both reactive processes and HLN present within analyzed LN could be identified and differentiated. Viability was more than 75% for all cryopreserved LN composed of haematolymphoid cells.

Conclusion:

The method presented in this study confers the possibility of storing fresh LN biopsies for later FCI, thus allowing a morphology‐based immunophenotypic approach. This would allow a more sensitive, specific, and cost‐effective management of LN specimens, whilst maintaining the important benefits provided by FCI. © 2012 International Clinical Cytometry Society
A Quantitative Systems Pharmacology Computer Model for Schizophrenia Efficacy and Extrapyramidal Side Effects
Authors: Spiros Athan , Roberts Patrick , Geerts Hugo
Published: April 2012

Strategy, Management and Health Policy

Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I‐III Regulatory, Quality, Manufacturing
Postmarketing Phase IV

Despite tremendous advances in understanding the neurobiology of schizophrenia, no real therapeutic breakthrough in terms of novel antipsychotics has been made since the serendipitous discovery of chlorpromazine. We describe a computer‐based mechanistic disease simulation model of biophysically realistic neurons that captures most of the subcortical neuromodulatory processes important in the pathophysiology of schizophrenia and calibrate this with a large retrospective clinical database for Positive and Negative Symptoms Scale in Schizophrenia (PANSS total) and extrapyramidal symptoms (EPS) liability. Additionally we make this platform more actionable for practical use in central nervous system drug discovery by introducing a synaptic receptor competition model that accurately captures clinical target exposures. The model accounts for threefold more variance than the simple dopamine D2 receptor occupancy rule and is also superior in a number of independent clinical data sets. As such, the model is a first step in a better understanding of the human neurobiology of schizophrenia. Using human pharmacology and a positron emission tomography target engagement study as input, the model can estimate a value for the clinical efficacy on PANSS total and EPS side effect liability for the clinical doses of a new investigative compound. This Quantitative Systems Pharmacology platform, by simulating the effect of co‐medications and genotypes in a clinical setting, represents a useful addition to psychiatric drug discovery efforts.
Tris(phosphonomethyl)cyclen Derivatives: Thermodynamic Stability, Kinetics, Solution Structure, and Relaxivity of Ln3+ Complexes
Authors: Lima Luís M. P. , Delgado Rita , Hermann Petr , Ševčík Radek , Lubal Přemysl , Carvalho Henrique F. , Martins André F. , Tóth Éva , Geraldes Carlos F. G. C.
Published: April 2012

The lanthanide (Ln3+) complexes of three cyclen‐based ligands containing three methylphosphonate pendant arms were studied, the ligands being 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triyltris(methylphosphonic acid) (H6do3p), 3‐[4,7,10‐tris(phosphonomethyl)‐1,4,7,10‐tetraazacyclododec‐1‐yl]propanoic acid (H7do3p1pr), and 10‐(3‐hydroxypropyl)‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triyltris(methylphosphonic acid) (H6do3p1ol). The three macrocyclic ligands form complexes of very high thermodynamic stability with all studied Ln3+ ions. Kinetic studies showed that the acid‐assisted dissociation of Ce3+ complexes of these ligands is much faster than for the complex of the related ligand H8dotp [1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(methylphosphonic acid)]. The number of water molecules coordinated to the Eu3+ and Gd3+ complexes was estimated to be < 1 for the do3p1ol ligand but ca. 1 for the other two ligands, as obtained by time‐resolved luminescence spectroscopy and by 1H and 17O relaxometric measurements. The NMR spectroscopic data indicate the existence of a considerable contribution from second‐sphere water molecules to the relaxivity of all the Gd3+ complexes studied. The 1H and 31P NMR spectra of the Eu3+, Yb3+ and Lu3+ complexes showed that the propionate arm in the [Ln(do3p1pr)]4– complexes and the propanol arm in the [Ln(do3p1ol)]3– complexes are not bound to the Ln3+ ion. The [Ln(do3p)]3– and [Ln(do3p1pr)]4– complexes have a clear preference for the TSAP (twisted square antiprismatic) isomer, while both SAP (square antiprismatic) and TSAP isomers are present in solutions of the [Ln(do3p1ol)]3– complexes.
Biocatalytic Approaches to the Henry (Nitroaldol) Reaction
Authors: Milner Sinéad E. , Moody Thomas S. , Maguire Anita R.
Published: April 2012

Enantiopure β‐nitro alcohols are key chiral building blocks for the synthesis of bioactive pharmaceutical ingredients. The preparation of these target compounds in optically pure form has been the focus of much research and there has been an emergence of biocatalytic protocols in the past decade. For the first time, these biotransformations are the focus of this review. Herein, we describe two principal biocatalytic approaches to the Henry (nitroaldol) reaction. The first method is a direct enzyme‐catalysed carbon–carbon bond formation resulting in either an enantio‐enriched or enantiopure β‐nitro alcohol. The second approach describes the Henry reaction without stereocontrol followed by a biocatalytic resolution to yield the enantiopure β‐nitro alcohol.
Synthesis, Photophysical Properties, and Field‐Effect Characteristics of (Ethynylphenyl)benzimidazole‐Decorated Anthracene and Perylene Bisimide Derivatives
Authors: Lee I‐Lin , Li Sie‐Rong , Chen Kuan‐Fu , Ku Po‐Jen , Singh Ashutosh S. , Kuo Hui‐Tung , Wen Yuh‐Sheng , Chu Chi‐Wei , Sun Shih‐Sheng
Published: April 2012

A series of anthracene and perylene bisimide derivatives with electron‐withdrawing benzimidazole substituents has been designed and prepared. Detailed studies on the electrochemical and photophysical properties as well as the field‐effect mobilities of these new compounds were explored. The incorporation of electron‐withdrawing benzimidazole groups lowered the LUMO levels in both anthracene and perylene bisimide derivatives compared to those of the parent compounds. Strong emission was observed for all anthracene derivatives, but only weak emission was observed for perylene bisimide derivatives. The anthracene derivatives showed typical p‐type semiconducting character, even when the derivatives were substituted with electron‐withdrawing benzimidazole groups at the 9‐ and 10‐positions, which apparently does not lower the LUMO levels to transform them into electron‐transporting molecules. Perylene bisimide derivatives displayed typical n‐channel semiconducting properties with low threshold voltages and electron mobilities of ca. 5.2 × 10–5 cm2 V–1 s–1.
Preparation of (E)‐4‐Aryl‐1,1,1‐trifluoro‐3‐tosylbut‐3‐en‐2‐ones as Fluorinated Building Blocks and Their Application in Ready and Highly Stereoselective Routes to trans‐2,3‐Dihydrofurans Substituted with Trifluoromethyl and Sulfonyl Groups
Authors: Yu Haigang , Han Jing , Chen Jie , Deng Hongmei , Shao Min , Zhang Hui , Cao Weiguo
Published: April 2012

(E)‐4‐Aryl‐1,1,1‐trifluoro‐3‐tosylbut‐3‐en‐2‐one fluorinated building blocks were prepared through a two‐step process. Treatment of these (E)‐4‐aryl‐1,1,1‐trifluoro‐3‐tosylbut‐3‐en‐2‐ones with arsonium bromides in the presence of Cs2CO3 in CH2Cl2 at reflux resulted in highly stereoselective ring closure to provide 4‐tosyl‐5‐trifluoromethyl‐trans‐2,3‐dihydrofurans in good to excellent yields.
Obsidian Subsource Identification in the Sierra de Pachuca and Otumba Volcanic Regions, Central Mexico, by ICP‐MS and DBSCAN Statistical Analysis
Authors: Argote‐Espino Denisse , Solé Jesús , López‐García Pedro , Sterpone Osvaldo
Published: April 2012

Otumba and Sierra de Pachuca obsidian deposits in Central Mexico have been important sources of raw material since pre‐Hispanic times. Numerous archaeological investigations have suggested that the economical and political expansion of major Mesoamerican societies were linked to the control of obsidian sources and distribution of quarried material. Sierra de Pachuca contains several obsidian flows and numerous quarries throughout the region that were preferentially exploited by different cultures. The Otumba Volcanic Complex has four important obsidian domes, but three of them have not been studied in detail. A geochemical characterization of subsources from the Sierra de Pachuca and Otumba Volcanic Complex is an important step toward future sourcing of obsidian artifacts that would help provide insight into spheres of influence and trade by past cultures in Central Mexico. Having this purpose in mind, inductively coupled plasma mass spectrometry (ICP‐MS) was used to analyze obsidian samples collected from five separated locations at Sierra de Pachuca and four at Otumba, followed by statistical analysis (density‐based spatial clustering of applications with noise, DBSCAN). We were able to distinguish three chemically distinctive subsources in Sierra de Pachuca and three in Otumba. This study illustrates the importance of accurate characterization of obsidian raw material when attempting to define subsource usage.
Environmental Change and Terrestrial Resource Use by theThule andInuit ofLabrador,Canada
Authors: Roy Natasha , Bhiry Najat , Woollett James
Published: April 2012

The object of this study is to document how theInuit on the northern coast ofLabrador,Canada used terrestrial resources such as peat and wood during theLittleIceAge (LIA;A.D.1500–1870). Paleoecological investigations consisting of pollen and macrofossil analyses were undertaken in conjunction with archaeological excavations at theInuit winter settlement sites ofOakesBay 1, located in theNain region of north‐centralLabrador. Our data indicate that the major changes in terrestrial ecosystems of this coastal region were triggered by climate change. From ca. 5700 to 3000 cal. yrB.P., climatic conditions were relatively warm and moist. At ca. 3000 cal. yrB.P.conditions became significantly drier and colder, which corresponds to broader climatic trends during theNeoglacial period. At ca. 1000 cal. yrB.P., the reappearance of hygrophilic species and the establishment ofLarix laricinaprovide evidence of a return to more humid conditions that in turn triggered the onset of the paludification of sandy terraces in theDogIsland region. Peat accumulation persisted after ca. 580 cal. yrB.P.likely due to the elevation of the frost table during theLIA. Elevated frost tables contributed to water saturation of the surface during the spring, creating conditions that were conducive to the preservation of organic material. Natural resources such as trees and peat were therefore readily available and more abundant during theLIAand extensively used by theInuit for house construction and heating in theDogIsland region.
Functional impairment, illness burden, and depressive symptoms in older adults: does type of social relationship matter?
Authors: Hatfield Joshua P. , Hirsch Jameson K. , Lyness Jeffrey M.
Published: April 2012

Objective

The nature of interpersonal relationships, whether supportive or critical, may affect the association between health status and mental health outcomes. We examined the potential moderating effects of social support, as a buffer, and family criticism, as an exacerbating factor, on the association between illness burden, functional impairment and depressive symptoms.

Methods

Our sample of 735 older adults, 65 years and older, was recruited from internal and family medicine primary care offices. Trained interviewers administered the Hamilton Rating Scale for Depression, Duke Social Support Inventory, and Family Emotional Involvement and Criticism Scale. Physician‐rated assessments of health, including the Karnofsky Performance Status Scale and Cumulative Illness Rating Scale, were also completed.

Results

Linear multivariable hierarchical regression results indicate that social interaction was a significant buffer, weakening the association between illness burden and depressive symptoms, whereas perceived social support buffered the relationship between functional impairment and depressive symptoms. Family criticism and instrumental social support were not significant moderators.

Conclusions

Type of medical dysfunction, whether illness or impairment, may require different therapeutic and supportive approaches. Enhancement of perceived social support, for those who are impaired, and encouragement of social interactions, for those who are ill, may be important intervention targets for treatment of depressive symptoms in older adult primary care patients. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of epidermal growth factor receptor and insulin‐like growth factor 1 receptor inhibition on proliferation and intracellular signaling in cutaneous SCCHN: Potential for dual inhibition as a therapeutic modality
Authors: Clayburgh Daniel R. , Gross Neil D. , Proby Charlotte , Koide Jade , Wong Melissa H.
Published: April 2012

Background

Combined inhibition of epidermal growth factor receptor (EGFR) and insulin‐like growth factor‐1 receptor (IGF‐1R) has been proposed as a therapy for cutaneous squamous cell carcinoma of the head and neck (SCCHN).

Methods

Receptor expression and downstream signaling were assessed in cutaneous squamous cell carcinoma (SCC) cell lines and patient samples. EGFR and IGF‐1R signaling was inhibited in cutaneous SCC cell lines using erlotinib and/or picropodophyllin.

Results

EGFR and IGF‐1R were overexpressed in cutaneous SCCHN specimens relative to normal skin. Dual inhibition of both receptors prevented cell growth and decreased activation of Akt and p42/44 mitogen‐activated protein kinase (MAPK) more effectively than either inhibitor alone.

Conclusion

Dual inhibition of EGFR and IGF‐1R is effective at blocking cell growth, and is correlated with inhibition of Akt and p42/44 MAPK, suggesting that this may be a promising treatment for cutaneous SCCHN. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Interstitial brachytherapy for lower lip carcinoma: Global assessment in a retrospective study of 89 cases
Authors: Rio Emmanuel , Bardet Etienne , Mervoyer Augustin , Piot Benoit , Dreno Brigitte , Malard Olivier
Published: April 2012

Background

Infiltrating squamous cell carcinoma (SCC) of the lower lip is a highly curable cancer. We retrospectively analyzed oncologic, functional, and cosmetic outcomes after interstitial low‐dose rate brachytherapy at 58 Gy (50–62) of lower lip SCC treated in our institution.

Methods

There were 89 patients (44 T1, 33 T2, 2 T3, and 10 after wedge‐excision). All tumors were N0 at the time of treatment. We calculated survival rates and assessed functional and cosmetic results de visu.

Results

After a median follow‐up of 36 months (range, 9–127), 5‐year local control rate was 95% and 5‐year disease‐free survival was 82%. Only 6 patients (5 T2 and 1 T3) developed secondary cervical nodal involvement. Sixty‐one patients were reassessed and 11 patients presented mild functional troubles. Cosmetic results were good (77%) or fair (21%).

Conclusion

Brachytherapy provided a high local disease control rate, excellent functional results, and good cosmetic outcomes for SCCs of the lip. Risk of cervical node involvement was low with small tumors. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Comparison of total laryngectomy with surgical (cricohyoidopexy) and nonsurgical organ‐preservation modalities in advanced laryngeal squamous cell carcinomas: A multicenter retrospective analysis
Authors: Bussu Francesco , Paludetti Gaetano , Almadori Giovanni , De Virgilio Armando , Galli Jacopo , Miccichè Francesco , Tombolini Mario , Rizzo Davide , Gallo Andrea , Giglia Veronica , Greco Antonio , Valentini Vincenzo , De Vincentiis Marco
Published: April 2012

Background

Functional outcome and quality of life (QOL) have become relevant endpoints in the field of laryngeal oncology, leading to the emergence of organ‐preserving strategies.

Methods

The medical records of 166 patients with advanced (stages III and IV) laryngeal squamous cell carcinoma (SCC) who were treated with a total laryngectomy, radiochemotherapy, or cricohyoidopexy (CHP) were reviewed.

Results

In the whole series, no statistically significant differences among the 3 treatment arms with respect to the overall survival (OS) and disease‐specific survival (DSS) rates were observed. The organ‐preservation rate was 45% for radiotherapy and 76.7% for CHP (p = .0002). Among the cT4a cases, a longer survival was observed for the patients treated with total laryngectomy (3 yr‐OS = 78% vs 68% for CHP and 54% for radiochemotherapy, p = .031).

Conclusions

In advanced laryngeal SCC, CHP shows survival rates comparable to those of radiochemotherapy and a higher larynx‐preservation rate, although it may not replace radiochemotherapy because it can be recommended only in selected cases. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Evaluation of the climate prediction center (CPC) morphing technique (CMORPH) rainfall product on hourly time scales over the source of the Blue Nile River
Authors: Haile Alemseged Tamiru , Habib Emad , Rientjes Tom
Published: April 2012

Limited availability of surface‐based rainfall observations constrains the evaluation of satellite rainfall products over many regions. Observations are also often not available at time scales to allow evaluation of satellite products at their finest resolutions. In the present study, we utilized a 3‐month rainfall data set from an experimental network of eight automatic gauges in Gilgel Abbay watershed in Ethiopia to evaluate the 1‐hourly, 8 × 8‐km Climate Prediction Center morphing technique (CMORPH) rainfall product. The watershed is situated in the Lake Tana basin which is the source of the Blue Nile River. We applied a suite of statistical metrics that included mean difference, bias, standard deviation of differences and measures of association. Our results indicate that the accuracy of the CMORPH product shows a significant variation across the basin area. Its estimates are mostly within ±10 mm h−1 of the gauge rainfall observations; however, the product does not satisfactorily capture the rainfall temporal variability and is poorly correlated (<0.27) to gauge observations. Its poor rain detection capability led to significant underestimation of the seasonal rainfall depth (total bias reaches up to −52%) with large amounts of hit rain bias as well as missed rain and false rain biases. In the future refinement of CMORPH algorithm, more attention should be given to reducing missed rain bias over the mountains of Gilgel Abbay, whereas equal attention should be given to hit, missed rain and false rain biases over other parts of the watershed. Copyright © 2012 John Wiley & Sons, Ltd.
Annual Review: Practice and Research in Career Counseling and Development—1996
Authors: Niles Spencer G.
Published: April 2012

The National Career Development Association's (NCDA) Professional Standards Committee (1997) has recently identified 11 competency areas (career development theory, individual and group counseling skills, individual and group assessment, information resources, and program management and implementation, consultation, diverse populations, supervision, ethical legal issues, and research evaluation, and technology). These competencies were used as categories for classifying research on career development and counseling published in 1996. Two primary areas of research activity were identified: making career counseling theory useful for more clients, and emphasizing the role of contextual factors in shaping career development. Four competency areas not addressed sufficiently by researchers were also identified: consultation, supervision, technology, and ethics. Implications for practice and future research are discussed.
Caught in Two Worlds: Jessica Chang From a Cross‐Cultural Perspective
Authors: Fouad Nadya A. , Tang Mei
Published: April 2012

This article conceptualizes the case of Jessica Chang from a cross‐cultural perspective. The article also suggests additional readings in cross‐cultural counseling, and specifically focuses on cross‐cultural career counseling The case is examined from the viewpoint of Jessica Chang, her supervisor, and the that of her organization as a whole. Practical implications for each participant are discussed.
The Case of Jessica Chang: A Business and Industry Perspective
Authors: Shahnasarian Michael
Published: April 2012

This discussion presents a business and industry perspective on Jessica Chang's career. Jessica's career issues are analyzed from an organizational perspective and from a career counseling perspective, with attention to salient cross‐cultural counseling issues. The discussion emphasizes actions that organizations can take to anticipate similar situations, and explores how Jessica could have better managed her career development in view of the challenges she encountered.
Efficacy and Outcome Expectations Influence Career Exploration and Decidedness
Authors: Betz Nancy E. , Voyten Karla Klein
Published: April 2012

In this multiple regression model, self‐efficacy beliefs are the best predictor of career indecision, and outcome expectations are the best predictor of exploration intentions. When indecision was entered as a predictor, it also was a significant predictor of exploration intentions—students who were less decided were also more likely to plan career exploration. Career efficacy and outcome expectations relate significantly more strongly within the group of college men than within the group of college women. Implications for social cognitive career theory and practice are discussed.
Experiential Training in Group Counseling: Humanistic Processes in Practice
Authors: OSBORN CYNTHIA J. , DANINHIRSCH CARRIE L. , PAGE BETSY J.
Published: April 2012

D. A. Kolb's (1984) 4 processes of experiential education are presented as guidelines for humanistically based training in group counseling. Specific training activities are described, and recommendations for improving training methods are outlined. The authors present qualitative data obtained from graduate counseling students who participated in these activities and provide recommendations for research.
Counseling Women With Severe Dis/Abilities: A Semiotic Perspective
Authors: STOCKALL NANCY , STICKELS DENA
Published: April 2012

This illustrative article describes how a semiotic perspective can illuminate and transcend traditional views of women with severe dis/abilities. A critical reading of signs within particular contexts can help position counselors and clients in a relationship that enhances mutual growth and development.
Career Paths of Professional Leaders in Counseling: Plans, Opportunities, and Happenstance
Authors: MAGNUSON SANDY , WILCOXON S. ALLEN , NOREM KEN
Published: April 2012

The authors conducted qualitative analyses of 10 counseling leaders' accounts of turning points in their professional development, turning points that led them to become leaders. The participants' explanations provided support for applying the planned happenstance theory of career development to leadership development.
Fabrication and characterization of novel nano hydroxyapatite/β‐tricalcium phosphate scaffolds in three different composition ratios
Authors: Ebrahimi Mehdi , Pripatnanont Prisana , Monmaturapoj Naruporn , Suttapreyasri Srisurang
Published: April 2012

The biphasic calcium phosphate (BCP) concept was introduced to overcome disadvantages of single phase biomaterials. Different composition ratios of BCP bioceramics have been studied, yet controversies regarding the effects of ratio on biomaterial behavior still exist. In this study, BCP scaffolds were prepared from nano hydroxyapatite (HA) and β‐tricalcium phosphate (β‐TCP) that were synthesized via a solid state reaction. Three different composition ratios of pure BCP and collagen‐based BCP scaffolds (%HA/%β‐TCP; 30/70, 40/60, and 50/50) were produced using a polymeric sponge method. Physical and mechanical properties of all materials and scaffolds were investigated. SEM showed overall distribution of both macropores (80–200 μm) and micropores (0.5–2 μm) with high interconnected porosities. Total porosity of pure BCP (90% ± 3%) was found to be higher than collagen‐based BCP (85% ± 2%). It was observed that following sintering process, dimensional shrinkage of large scaffolds (39% ± 4%) was lower than small ones (42% ± 5%) and scaffolds with high HA ratios (50%) experienced higher dimensional changes than those with higher β‐TCP (70%) ratios (45% ± 3% and 36% ± 1%, respectively). Compressive strength of both groups was less than 0.1 MPa and collagen coating had almost no influence on mechanical behavior. Further studies may improve the physical properties of these scaffolds and investigate their exact biological behaviors. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2260–2268, 2012.
The in vivo osteogenesis of Mg or Zr‐modified silicate‐based bioceramic spheres
Authors: Luo Tao , Wu Chengtie , Zhang Yufeng
Published: April 2012

The use of bioactive microspheres as bone filling materials has received much attention due to their ability to fill the bone defects with irregular and complex shapes and sizes. Divalent Mg2+ modified silicate‐based diopside (DIOP: CaMgSi2O6) and tetravalent Zr4+ modified silicate‐based baghdadite (BAGD: Ca3ZrSi2O9) ceramics have shown excellent in vitro bioactivity for potential bone repair application. However, their in vivo osteogenesis has not been systematically investigated. The aim of this study is to prepare DIOP and BAGD ceramic microspheres and investigate their in vivo osteogenesis. DIOP and BAGD ceramic spheres with loose microstructure were successfully prepared. The dissolution ability of two silicate‐based bioceramics was investigated by testing the release of SiO ions after soaking them in phosphate buffered saline. The ceramic spheres were implanted into supracondylar site of the femur defects in Wistar rats and the degree of in vivo osteogenesis was evaluated by hematoxylin and eosin (H and E), Safranin O staining, tartrate‐resistant acid phosphatase (TRAP) staining, and immunohistochemistry (type I collagen: Col I, osteopontin: OPN) analyses. The results have shown that BAGD spheres induced a higher rate of new bone formation in the defects than did DIOP and β‐tricalcium phosphate (β‐TCP) spheres. Immunohistochemical analysis showed greater expression of Col I and OPN in BAGD group compared to DIOP and β‐TCP groups. The study indicates different ion modification playing an important role to regulate the in vivo osteogenesis of silicate‐based bioceramics. BAGD spheres are a promising bone filler material due to their significantly enhanced osteogenesis, compared to β‐TCP spheres. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2269–2277, 2012.
The controlled release of vancomycin in gelatin/β‐TCP composite scaffolds
Authors: Zhou Jian , Fang Taolin , Wang Yichao , Dong Jian
Published: April 2012

Osteomyelitis remains a difficult infection to treat for orthopaedic surgeons regardless of the continuous advances in surgical techniques and antimicrobial agents. The controlled release of vancomycin from local delivery system is a promising method for eliminating infection. In this study, biodegradable gelatin sponge containing different contents of β‐tricalcium phosphate ceramic (β‐TCP) was prepared for the controlled‐release of vancomycin. We aimed to confirm the composite scaffolds could be used as a vancomycin sustained‐release system. Examinations of scanning electron microscopy, Fourier transform infrared spectroscopy, mechanical properties, and in vivo drug release were performed. The results showed that the composite scaffolds could achieve local therapeutic drug levels over an extended duration. Taking consideration of porosity, interconnection, mechanical properties, and controlled release performance, the composite gelatin scaffold containing 30% β‐TCP granules may be a good candidate for the controlled release of vancomycin in the treatment of chronic osteomyelitis. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2295–2301, 2012.
Effect of interprotein polarization on protein–protein binding energy
Authors: Ji Chang G. , Zhang John Z. H.
Published: April 2012

Molecular dynamics simulation in explicit water for the binding of the benchmark barnase‐barstar complex was carried out to investigate the effect polarization of interprotein hydrogen bonds on its binding free energy. Our study is based on the AMBER force field but with polarized atomic charges derived from fragment quantum mechanical calculation for the protein complex. The quantum‐derived atomic charges include the effect of polarization of interprotein hydrogen bonds, which was absent in the standard force fields that were used in previous theoretical calculations of barnase‐barstar binding energy. This study shows that this polarization effect impacts both the static (electronic) and dynamic interprotein electrostatic interactions and significantly lowers the free energy of the barnase‐barstar complex. © 2012 Wiley Periodicals, Inc.
Couple Therapy for Depression
Authors: Whisman Mark A. , Beach Steven R. H.
Published: April 2012

Relationship problems and depression often influence one another in a bidirectional, recursive fashion. Results from several clinical trials have demonstrated that couple therapy is effective in improving depression and reducing relationship problems. In this article, we describe an approach to working with depression in partnered individuals who are also unhappy in their relationship. This cognitive‐behavior approach strives to (a) eliminate major stressors and reestablish positive activities in the relationship, (b) improve communication and problem solving in the relationship, and (c) solidify gains made in therapy and prevent relapse. The typical course of therapy is described and demonstrated in a case illustration. Couple therapy is a promising treatment for depressed individuals in distressed relationships.
Percentage of gutta‐percha in mesial canals of mandibular molars obturated by lateral compaction or single cone techniques
Authors: Rodrigues Amanda , Bonetti‐Filho Idomeo , Faria Gisele , Andolfatto Carolina , Camargo Vilella Berbert Fábio Luiz , Kuga Milton Carlos
Published: April 2012

The aim of this study was to compare the percentage of gutta‐percha (PGP) in mesial root canals of mandibular molars obturated with LC (Lateral Compaction) or SC (Single Cone) ProTaper Universal System techniques at different levels of the root. Mesial root canals of 20 human permanent molars with similar anatomical characteristics were instrumented using the ProTaper Universal rotary system technique until the F2 instrument, with 20 canals filled by SC ProTaper Universal technique and 20 canals by the LC technique. The mesial roots were sectioned transversely to 3, 5, and 7 mm from the root apex. Digital images of specimens were obtained at MIC‐D digital microscope in increases of 30 to 35X. The gutta‐percha area was measured using ImageTool software. Data were analyzed using two‐way ANOVA and Bonferroni test (α = 0.05). The SC technique provided greater PGP than the LC technique in the apical third (3 mm) (P < 0.001). In the other thirds (5 and 7 mm) there was no statistical difference between the two techniques regarding the PGP (P > 0.05). There was no statistically significant difference between thirds of the root canal for both techniques (P > 0.05). It was concluded that SC technique provided greater PGP than the LC technique in the apical third of mesial root canals of mandibular molars. There was no difference between the two techniques regarding the PGP in the cervical and middle thirds. Microsc. Res. Tech. 75:1229–1232, 2012. © 2012 Wiley Periodicals, Inc.
Lentiviral vectors encoding short hairpin RNAs efficiently transduce and knockdown LINGO‐1 but induce an interferon response and cytotoxicity in central nervous system neurones
Authors: Hutson Thomas H. , Foster Edmund , Dawes John M. , Hindges Robert , Yáñez‐Muñoz Rafael J. , Moon Lawrence D. F.
Published: April 2012

Background

Knocking down neuronal LINGO‐1 using short hairpin RNAs (shRNAs) might enhance axon regeneration in the central nervous system (CNS). Integration‐deficient lentiviral vectors have great potential as a therapeutic delivery system for CNS injuries. However, recent studies have revealed that shRNAs can induce an interferon response resulting in off‐target effects and cytotoxicity.

Methods

CNS neurones were transduced with integration‐deficient lentiviral vectors in vitro. The transcriptional effect of shRNA expression was analysed using quantitative real time‐polymerase chain reaction and northern blots were used to assess shRNA production.

Results

Integration‐deficient lentiviral vectors efficiently transduced CNS neurones and knocked down LINGO‐1 mRNA in vitro. However, an increase in cell death was observed when lentiviral vectors encoding an shRNA were applied or when high vector concentrations were used. We demonstrate that high doses of vector or the use of vectors encoding shRNAs can induce an up‐regulation of interferon‐stimulated genes (2′,5′‐oligoadenylate synthase 1 and protein kinase R although not myxovirus resistance 1) and a down‐regulation of off‐target genes (including p75NTR and Nogo receptor 1). Furthermore, the northern blot demonstrated that these negative consequences occur even when lentiviral vectors express low levels of shRNAs. Taken together, these results may explain why neurite outgrowth was not enhanced on an inhibitory substrate following transduction with lentiviral vectors encoding an shRNA targeting LINGO‐1.

Conclusions

These findings highlight the importance of including appropriate controls to verify silencing specificity and the requirement to check for an interferon response when conducting RNA interference experiments. However, the potential benefits that RNA interference and viral vectors offer to gene‐based therapies to CNS injuries cannot be overlooked and demand further investigation. Copyright © 2012 John Wiley & Sons, Ltd.
Broad respiratory virus detection in infants hospitalized for bronchiolitis by use of a multiplex RT‐PCR DNA microarray system
Authors: Huguenin Antoine , Moutte Lauryane , Renois Fanny , Leveque Nicolas , Talmud Deborah , Abely Michel , Nguyen Yohan , Carrat Fabrice , Andreoletti Laurent
Published: April 2012

Newly available molecular tools allow a sensitive detection of a broad panel of viruses in respiratory tract specimens. In the present study, the application of a multiplex RT‐PCR DNA microarray in diagnosis and epidemiological survey of viral infections in infants hospitalized for bronchiolitis was assessed. One hundred and thirty‐eight nasopharyngeal aspirates collected from October 2007 to September 2008 were tested by direct immunofluorescence and viral culture, a combination of referenced RT‐PCRs and the DNA microarray. One or more viruses were detected in 96, 126 and 126 of the specimens by direct immunofluorescence and viral culture, RT‐PCRs and DNA microarray, respectively (70 vs. 91 vs. 91%, P < 10−3). The RT‐PCRs and the DNA microarray yielded concordant results for 99% of specimens and identified mixed viral infections in 85 (62%). The most common associations were: human bocavirus and respiratory syncytial virus (32%), adenovirus and respiratory syncytial virus (30%), and parainfluenza virus type 3 and respiratory syncytial virus (23%). None of the bronchiolitis severity parameters including intensive care unit admission, O2 supply, O2 saturation percentage, O2 length and length of stay at the hospital appeared to be significantly increased in multiple viral infections compared to single viral infections (P > 0.1). In conclusion, the use of this DNA microarray in clinical virology practice allows rapid and accurate identification of common and uncommon viral respiratory pathogens in infants hospitalized for bronchiolitis. It should improve the clinical management, the epidemiological survey, and the prevention of the nosocomial transmission of respiratory viruses in pediatric wards. J. Med. Virol. 84:979–985, 2012. © 2012 Wiley Periodicals, Inc.
Two years outcome of women infected with high risk HPV having normal colposcopy following low‐grade or equivocal cytological abnormalities: Are HPV16 and 18 viral load clinically useful predictive markers?
Authors: Carcopino Xavier , Henry Mireille , Mancini Julien , Giusiano Sophie , Boubli Léon , Olive Daniel , Tamalet Catherine
Published: April 2012

Management of patients infected with high‐risk HPV (hrHPV) despite normal colposcopy following abnormal cytology remains a clinical challenge. The aim of this study was to evaluate if, in that specific population, initial HPV 16 and HPV 18 viral loads are predictive of infection clearance over a 24‐month follow‐up. A total of 67 women infected with hrHPV having normal colposcopy following equivocal or low‐grade cytological abnormalities were recruited and attended regular follow‐ups based on repeat colposcopies and HPV testing. HPV16 and HPV18 infection were diagnosed in 36 (53.7%) and 7 (10.4%) cases, respectively. Viral load was quantified using the quantitative duplex real‐time PCR method. Although this was not observed for HPV 18, initial HPV 16 viral load was highly associated to HPV 16 infection outcome (receiver operating characteristic curve analysis, area under curve: 0.90). Thus, women who had cleared their HPV 16 infection had significantly lower median initial HPV 16 viral load than those with persistent HPV 16 infection: 1.5 × 103 copies per million cells (CPMC) versus 3.8 × 106 CPMC, respectively (P = 0.006). The best prediction of HPV 16 clearance was obtained with an initial HPV 16 viral load of <7.5 × 104 CPMC: 86.7% specificity and 85.7% sensitivity. Finally, six patients were diagnosed with grade 2 or 3 cervical or vaginal intraepithelial neoplasia. Although all had a persistent hrHPV infection, neither HPV 16 nor 18 viral loads were found to be predictive of the risk of cervical or vaginal intraepithelial neoplasia. HPV16 viral load quantitation could represent a clinically useful marker in that very specific population. J. Med. Virol. 84:964–972, 2012. © 2012 Wiley Periodicals, Inc.
Prevalence of hepatitis B virus infection in a highly endemic area of southern China after catch‐up immunization
Authors: Fang Zhong‐Liao , Harrison Tim J. , Yang Jin‐Ye , Chen Qin‐Yan , Wang Xue‐Yan , Mo Jian‐Jun
Published: April 2012

The Chinese national goals for control of hepatitis B virus (HBV) infection were to achieve a prevalence of HBsAg below 7% for the entire population, and 1% for children under 5‐year old, by 2010. To determine whether Guangxi, a multi‐minority province with a low socio‐economic status and a very high prevalence of HBV, achieved this goal, a seroepidemiological survey of HBV infection was carried out using stratified, random cluster sampling. The results show that the overall prevalence of HBsAg is 9.16% [95% confidence interval (CI) = 8.32–10%]. The prevalence in males (10.96%, 95% CI = 9.64–12.28%) is significantly higher than in females (7.71%, 95% CI = 6.64–8.78%; χ2 = 10.5923, P < 0.05). The prevalence in children under 5‐year old is 3.62% (95% CI = 0.60–6.64%) and increases with age. The prevalence of HBsAg in non‐immunized individuals is significantly higher than in those immunized completely, although not within 24 hr of birth (χ2 = 31.426, P < 0.05); a significant difference was found in those below the age of 20 years but not in older persons. Gender, age, immunization history, and familial HBsAg carriers are risk factors for infection. In conclusion, this study indicates that Guangxi has not reached the goal for the control of HBV infection. Catch‐up HBV immunization may not protect adults effectively against infection in highly endemic regions. J. Med. Virol. 84:878–884, 2012. © 2012 Wiley Periodicals, Inc.
Case Report: Risk of virus infection after accidental blood inoculation from a multi‐infected AIDS patient
Authors: Berger Annemarie , Stürmer M. , Doerr H.W.
Published: April 2012

Infections caused by blood‐borne viruses such as hepatitis B and C and the human immunodeficiency virus (HIV) are associated commonly with needlestick injuries, especially in a hospital setting. A prospective investigation was conducted on a medical doctor who suffered an accidental needlestick injury during blood collection from a patient with AIDS.

The patient's blood contained 195,000 copies of HIV RNA, 1 × 106 IU hepatitis C virus (HCV) RNA, and >107 copies of parvovirus B19 DNA per 1 ml plasma. It was positive for cytomegalovirus virus and evidence of a resolved hepatitis B virus (HBV) infection was found. HCV viremia was detected in the physician 15 days later and was not resolved by seroconversion after 57 days. HIV infection was not transmitted, possibly because of the immediate use of anti‐HIV prophylactic drugs after exposure. Parvovirus B19 infection was presumably prevented by pre‐existing specific antibodies in the patient.

Considering that many HIV carriers are coinfected with hepatitis B and C viruses, this case report support the knowledge that the risk of HCV transmission from a patient with AIDS is greater than that of HIV. J. Med. Virol. 84:897–900, 2012. © 2012 Wiley Periodicals, Inc.
Valuing Tourist Destinations: an Oaxaca‐Blinder Approach
Authors: Vilchez Josep Raya
Published: April 2012

Destination branding influences destination selection process and future tourist behaviors. However, measuring brand equity is difficult in the case of tourist destinations. The aim of this paper is to determine which part of the price of a tourist service can be explained by differences in characteristics and which part can be explained by differences in destination branding. Data from Catalonia, Valencia, the Balearic Islands and Languedoc‐Roussillon are used as well as the Oaxaca‐Blinder decomposition method. More than a half of the gap (between prices paid by French and Spanish tourists for an equivalent hotel) can be attributed to destination branding. Copyright © 2012 John Wiley & Sons, Ltd.
Disease‐specific quality of life outcomes in functional rhinoplasty
Authors: Lindsay Robin W.
Published: April 2012

Objectives/Hypothesis:

The goal of this study was to assess disease‐specific quality of life as well as cosmetic outcomes following functional rhinoplasty in adults with nasal obstruction.

Study Design:

Prospective observational outcomes study.

Methods:

Disease‐specific quality of life determinations and cosmetic outcome assessments were performed using the Nasal Obstruction Symptom Evaluation scale (NOSE), the Sleep Outcomes Survey (SOS), and a cosmetic outcomes scale. Ratings were ascertained preoperatively and postoperatively at 1 to 3 and at 6 to 12 months for patients with internal nasal valve dysfunction, external nasal valve dysfunction, and both (groups 1, 2, and 3, respectively).

Results:

All groups showed a significant improvement in NOSE scores at the early and the late time points (P < .0005). SOS scores significantly improved from baseline to 1–3 months after surgery (P < .0005) and to 6–12 months (P < .0005). Snoring cessation was reported in 30% of patients who snored preoperatively. The cosmetic appearance of the nose significantly improved after surgery (P < .0005).

Conclusions:

This study utilized standardized terminology to diagnosis and treat nasal valve dysfunction, and validated disease‐specific quality of life measures to quantify the improvements made with specific techniques. In particular, this study showed improvement in nasal obstruction and snoring in patients with nasal valve dysfunction treated surgically, without negatively impacting nasal cosmesis. Studies utilizing consistent methods of assessment and analysis will allow for future meta‐analysis, increasing the level of evidence available in the field of functional rhinoplasty, and facilitate the creation of evidence‐based management algorithms. Laryngoscope, 2012
Radiographic enhancement of the nasoseptal flap does not predict postoperative cerebrospinal fluid leaks in endoscopic skull base reconstruction
Authors: Adappa Nithin D. , Learned Kim O. , Palmer James N. , Newman Jason G. , Lee John Y. K.
Published: April 2012

Objectives/Hypothesis:

Cerebrospinal fluid (CSF) leaks continue to be the most common postoperative complication in expanded endonasal skull base procedures. Currently, a multilayer closure using a vascularized nasoseptal flap is most commonly performed for large ventral skull base defects in an effort to avoid postoperative CSF leaks. We correlated nasoseptal flap enhancement with postoperative CSF leak rates in a group of skull base reconstruction patients. The nasoseptal flap enhancement was determined by immediate postoperative gadolinium‐enhanced magnetic resonance imaging (MRI), which allowed for imaging of the flap's vascular pedicle. Our aim was to identify whether nasoseptal flap enhancement contributed to reduction of postoperative CSF leak rates.

Study Design:

Retrospective cohort study.

Methods:

We reviewed 19 patients who underwent expanded endoscopic resections of skull base lesions of advanced complexity. We calculated the incidence of CSF leaks and measured the presence of nasoseptal flap enhancement.

Results:

Of the 19 patients with immediate postoperative MRIs, three developed postoperative CSF leaks. All three CSF leaks were in cases with enhancing vascular pedicles. In contrast, we had three patients without evidence of flap enhancement, none of whom developed a postoperative CSF leak (Fisher exact test, P = 1.0). CSF leak was associated with posterior fossa lesions (P = .25). Nasoseptal flap enhancement was associated with younger age (P = .15).

Conclusions:

This retrospective cohort study demonstrates that although the vascularized pedicled nasoseptal flap is effective for closure of expanded endonasal skull base procedures, our experience found the actual enhancement of the flap itself does not appear to effect postoperative CSF leak rates. Laryngoscope, 2012
Synthesis and Characterization of Monodisperse Thermosensitive Dumbbell‐Shaped Microgels
Authors: Chu Fangfang , Siebenbürger Miriam , Polzer Frank , Stolze Carmen , Kaiser Julian , Hoffmann Martin , Heptner Nils , Dzubiella Joachim , Drechsler Markus , Lu Yan , Ballauff Matthias
Published: April 2012

Monodisperse thermosensitive dumbbell‐shaped core‐shell microgels are fabricated, which consist of a polystyrene core with a cross‐linked poly (N‐isopropylacrylamide) shell. The morphology of the microgels was investigated through cryogenic transmission electron microscopy and depolarized dynamic light scattering. The effective volume fraction and aspect ratio of the system could be adjusted through the swelling of the thermosensitive shell. We observe a phase transition of the microgels to an ordered, crystal‐like state, which is apparent through Bragg‐reflections in the visible range. These observations are further supported by rheological measurements where the shear‐melting of the crystal phase is clearly detected.