bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermediate Clinical Outcome of Bryan Cervical Disc Replacement for Degenerative Disk Disease and Its Effect on Adjacent Segment Disks
Authors: Ding Chen , Hong Ying , Liu Hao , Shi Rui , Hu Tao , Li Tao
Published: June 2012

The purpose of this study was to determine the intermediate clinical and radiographic outcomes of Bryan Cervical Disc (Medtronic Sofamor Danek, Inc, Memphis, Tennessee) replacement for the treatment of cervical degenerative disk disease and its effect on adjacent levels. Between November 2004 and December 2007, thirty-four patients (38 disks) underwent Bryan Cervical Disc replacement in the authors’ hospital. The authors retrospectively analyzed the records of 32 patients who completed follow-up. Outcome data were collected preoperatively; at 3, 12, 24 months postoperatively; and at last follow-up, which ranged from 32 to 69 months (average, 49.4 months). Clinical outcome, radiographic outcome, adjacent segment degeneration, complications, and reoperations were evaluated. The SF-36 physical component, SF-36 mental component, Neck Disability Index, Japanese Orthopaedic Association score, and neck/arm pain visual analog pain scale scores were all improved significantly at each postoperative time point compared with preoperative values (
P
<.05), but no statistically significant differences were noted between postoperative time points (
P
>.05). The postoperative flexion–extension range of motion of the operative site and adjacent segments were not significantly different from the preoperative values (
P
>.05) and were approximately the same for each postoperative time point (
P
>.05). A new degeneration scoring system demonstrated that approximately 23% of the adjacent levels displayed mild degeneration at last follow-up. However, degeneration did not affect the clinical outcomes. Prosthesis-related complications were rare, and no reoperations were performed. Bryan Cervical Disc replacement achieves satisfactory mid-term clinical and radiographic outcomes. The authors observed the progression of adjacent segment degeneration postoperatively, although no degradation of clinical outcomes occurred.
Rivaroxaban, an Oral, Direct Factor Xa Inhibitor: A New Option for Thromboprophylaxis
Authors: Kwong Louis M.
Published: June 2012

Patients undergoing major orthopedic surgery, including total hip arthroplasty (THA) and total knee arthroplasty (TKA), are at high risk for developing venous thromboembolism (VTE). Although largely a preventable complication, VTE develops in a significant proportion of patients, highlighting the need for improved methods of VTE prevention. Current thromboprophylactic options are limited by unpredictable pharmacokinetics and pharmacodynamics (vitamin K antagonists), parenteral/subcutaneous administration (heparin and low-molecular-weight heparins), complicated dosing, and increased risk of bleeding.

Rivaroxaban is an oral, direct Factor Xa inhibitor that has recently received marketing authorization in the United States for prophylaxis of deep vein thrombosis in patients undergoing hip or knee replacement surgery. The clinical pharmacology of rivaroxaban supports a convenient, oral, once-daily dosing regimen without the need for routine coagulation monitoring after THA or TKA. A comprehensive phase II and III study program supports its safety and efficacy for VTE prevention after THA or TKA. Phase III results have demonstrated the superior efficacy of rivaroxaban regimens compared with enoxaparin regimens, with similar rates of major bleeding. This article provides an overview of the phase II and III results that support the use of this agent for the prevention of VTE after elective total hip or knee replacement.
All-arthroscopic Anatomic Repair of an Avulsed Popliteus Tendon in a Multiple Ligament–injured Knee
Authors: Salzler Matthew J. , Martin Scott D.
Published: June 2012

Multiple ligament–injured knees are a heterogeneous group of knee injuries that lack a clear consensus on optimal treatment. Current areas of controversy include optimal timing of surgery, ligamentous repair vs reconstruction, and combined vs staged procedures. In addition, multiple open, arthroscopic, and arthroscopic-assisted techniques exist for repair and reconstruction of the injured stabilizers of the knee.

Many open posterolateral corner reconstruction techniques have been described, and this article represents the first description of an arthroscopic technique for repair of an avulsed popliteus tendon. This was performed with a standard anterolateral portal in addition to anterior and posterior superolateral portals. Nonabsorbable sutures were passed through the avulsed popliteus tendon in an outside-in technique using a suture shuttle. The nonabsorbable sutures were threaded though a tibial Beath pin, which was then passed through the prepared popliteus footprint and brought out medially. The final position of the popliteus was confirmed arthroscopically, and the sutures were tied medially over a screw post with a washer.

Arthroscopic popliteus repair has many possible advantages. Because the popliteus tendon insertion is intracapsular, open repair necessitates a capsulotomy, with the potential for complications such as postoperative wound drainage, intra-articular sinus formation, infection, and stiffness. Arthroscopic repair may avoid these complications. The current case was performed in conjunction with an open but extracapsular posterolateral corner repair. Further experience with this technique is required to determine its safety and efficacy.
Effect of Topographic Cone Location on Outcomes of Corneal Collagen Cross-linking for Keratoconus and Corneal Ectasia
Authors: Greenstein Steven A. , Fry Kristen L. , Hersh Peter S.
Published: June 2012

PURPOSE:

To assess the effect of preoperative topographic cone location on 1-year outcomes of corneal collagen cross-linking (CXL).

METHODS:

In this prospective, randomized, controlled clinical trial, 99 eyes (66 keratoconus, 33 ectasia) from 76 patients underwent CXL. Cone location was defined by the coordinates of preoperative maximum keratometry (maximum K) using the anterior sagittal curvature topography map (Pentacam, Oculus Optikgeräte GmbH). Patients were divided into three groups: those with a maximum K located within the central 3-mm (central cone group), 3- to 5-mm (paracentral cone group), and outside the 5-mm (peripheral cone group) optical zones. Topography and visual acuity data were obtained preoperatively and at 1 year.

RESULTS:

In the combined cohort, maximum K and uncorrected and corrected distance visual acuity significantly improved by −1.60±3.40 diopters (D) (
P
<.001), −0.08±0.25 logMAR (
P
=.001), and −0.10±0.18 log-MAR (
P
<.001), respectively. Comparing cone groups, maximum K decreased by 2.60±4.50 D (
P
<.001) in the central cone group, 1.10±2.50 D (
P
=.02) in the paracentral cone group, and 0.40±1.20 D (
P
=.08) in the peripheral cone group. Differences among groups were statistically significant (
P
<.001). Uncorrected distance visual acuity improved by −0.07±0.3 logMAR (
P
=.1) (central cone group), −0.1±0.17 logMAR (
P
=.004) (paracentral cone group), and −0.1±0.25 logMAR (
P
=.04) (peripheral cone group). Corrected distance visual acuity improved by −0.14±0.21 logMAR (
P
<.001) (central cone group), −0.08±0.17 logMAR (
P
=.01) (paracentral cone group), and −0.08±0.12 logMAR (
P
=.002) (peripheral cone group). For both UDVA and CDVA outcomes, these differences among groups were not statistically significant.

CONCLUSIONS:

After CXL, more topographic flattening occurs in eyes with centrally located cones and the least flattening effect occurs when the cone is located peripherally. This cone-location effect is found in eyes with both keratoconus and ectasia.
Depth of Focus Through Different Intraocular Lenses in Patients With Different Corneal Profiles Using Adaptive Optics Visual Simulation
Authors: Ruiz-Alcocer Javier , Pérez-Vives Cari , Madrid-Costa David , García-Lázaro Santiago , Montés-Micó Robert
Published: June 2012

PURPOSE:

To evaluate the depth of focus with monofocal intraocular lenses (IOLs) in patients with different corneal profiles using adaptive optics (AO) visual simulation.

METHODS:

An AO visual simulator (crx1, Imagine Eyes) was used to simulate the aberration pattern of three monofocal IOLs (Acrysof IQ SN60WF [Alcon Laboratories Inc]; Akreos Adapt AO [Bausch & Lomb]; and Triplato [AJL Ophthalmic]) of different optic designs. Five groups were considered: patients without any corneal refractive surgery (normal cornea group) and with prior low and high myopic and hyperopic ablations (low myopic ablation, high myopic ablation, low hyperopic ablation, and high hyperopic ablation groups). Defocus curves for all situations were measured, with the target being moved from −5.00 to +2.50 diopters (D) in 0.25-D steps, and visual acuity was measured at all vergences.

RESULTS:

Ten eyes from 10 patients were evaluated. The higher residual spherical aberration (SA) for all IOLs was obtained for the high myopic ablation group and the most negative residual SA was obtained for the high hyperopic ablation group. The best compromise between distance visual and depth of focus for the normal cornea, low myopic ablation, and high myopic ablation groups was obtained with the aspheric designs, whereas the best results for the low hyperopic and high hyperopic ablation groups were obtained with the spherical IOL.

CONCLUSIONS:

The results of this study suggest that the better compromise between distance visual acuity and depth of focus with the three IOLs and the different corneal profiles relies on a certain amount of positive SA. Above a certain limit of residual SA (positive or negative), visual acuity decreases at all vergences, worsening the depth of focus.
EWI-2 Association with α-Actinin Regulates T Cell Immune Synapses and HIV Viral Infection
Authors: Gordón-Alonso Mónica , Sala-Valdés Mónica , Rocha-Perugini Vera , Pérez-Hernández Daniel , López-Martín Soraya , Ursa Angeles , Álvarez Susana , Kolesnikova Tatiana V. , Vázquez Jesús , Sánchez-Madrid Francisco , Yáñez-Mó María
Published: June 2012

EWI motif-containing protein 2 (EWI-2) is a member of the Ig superfamily that links tetraspanin-enriched microdomains to the actin cytoskeleton. We found that EWI-2 colocalizes with CD3 and CD81 at the central supramolecular activation cluster of the T cell immune synapse. Silencing of the endogenous expression or overexpression of a cytoplasmic truncated mutant of EWI-2 in T cells increases IL-2 secretion upon Ag stimulation. Mass spectrometry experiments of pull-downs with the C-term intracellular domain of EWI-2 revealed the specific association of EWI-2 with the actin-binding protein α-actinin; this association was regulated by PIP2. α-Actinin regulates the immune synapse formation and is required for efficient T cell activation. We extended these observations to virological synapses induced by HIV and found that silencing of either EWI-2 or α-actinin-4 increased cell infectivity. Our data suggest that the EWI-2–α-actinin complex is involved in the regulation of the actin cytoskeleton at T cell immune and virological synapses, providing a link between membrane microdomains and the formation of polarized membrane structures involved in T cell recognition.
Omalizumab: Clinical Use for the Management of Asthma
Authors: Thomson Neil C. , Chaudhuri Rekha
Published: June 2012

Omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, is a treatment option for patients with moderate to severe allergic asthma whose asthma is poorly controlled with inhaled corticosteroids and inhaled long-acting β2agonist bronchodilators. This review considers the mechanism of action, pharmacokinetics, efficacy, safety and place in management of omalizumab in asthma and focuses particularly on key articles published over the last three years. Omalizumab reduces IgE mediated airway inflammation and its effect on airway remodeling is under investigation. Recent long-term clinical trials confirm the benefits of omalizumab in reducing exacerbations and symptoms in adults and in children with moderate to severe allergic asthma. No clinical or immunological factor consistently predicts a good therapeutic response to omalizumab in allergic asthma. In responders, the duration of treatment is unclear. The main adverse effect of omalizumab is anaphylaxis, although this occurs infrequently. Preliminary data from a five-year safety study has raised concerns about increased cardiovascular events and a final report is awaited. Clinical trials are in progress to determine whether omalizumab has efficacy in the treatment of non-allergic asthma.
Usability of optical spectrum analyzer in measuring atmospheric CO2 and CH4 column densities: substantiation with FTS and aircraft profiles in situ
Authors: Kawasaki M. , Yoshioka H. , Jones N. B. , Macatangay R. , Griffith D. W. T. , Kawakami S. , Ohyama H. , Tanaka T. , Morino I. , Uchino O. , Ibuki T.
Published: June 2012

Abstract. The practical usefulness of a desktop optical spectrum analyzer (OSA) for measuring atmospheric CO2 and CH4 column densities at surface sites was examined in two separate measurement campaigns. The first involved a long term measurement in parallel with a high resolution Fourier transform spectroscopy (FTS) studies at the University of Wollongong in Australia. Scale factors of the OSA were assigned for the column average volume mixing ratios of xCO2 and xCH4 by comparing with the well-studied FTS. The second method is a calibration against aircraft CO2 profiles in situ over Tsukuba in Japan obtained during a GOSAT validation campaign carried out from 28 January to 7 February 2011. The xCO2 values in the campaign, deduced by use of a derived OSA scale factor, were in excellent agreement with the integrated aircraft profiles.
A Proposed Instructional Theory for Integer Addition and Subtraction
Authors: Stephan Michelle , Akyuz Didem
Published: June 2012

This article presents the results of a 7th-grade classroom teaching experiment that supported students' understanding of integer addition and subtraction. The experiment was conducted to test and revise a hypothetical learning trajectory so as to propose a potential instructional theory for integer addition and subtraction. The instructional sequence, which was based on a financial context, was designed using the Realistic Mathematics Education theory. Additionally, an empty, vertical number line (VNL) is posited as a potentially viable model to support students' organizing their addition and subtraction strategies. Particular emphasis is placed on the mathematical practices that were established in this setting. These practices indicate that students can successfully draw on their experiences with assets, debts, and net worths to create meaning for integer addition and subtraction.
Effect of home‐based HIV counselling and testing on stigma and risky sexual behaviours: serial cross‐sectional studies in Uganda
Authors: Nuwaha Fred , Kasasa Simon , Wana Godwill , Muganzi Elly , Tumwesigye Elioda
Published: June 2012

Background

A large, district‐wide, home‐based HIV counselling and testing (HBHCT) programme was implemented in Bushenyi district of Uganda from 2004 to 2007. This programme provided free HBHCT services to all consenting adults of Bushenyi district and had a very high uptake and acceptability. We measured population‐level changes in knowledge of HIV status, stigma and HIV‐risk behaviours before and after HBHCT to assess whether widespread HBHCT had an effect on trends of risky sexual behaviours and on stigma and discrimination towards HIV.

Methods

Serial cross‐sectional surveys were carried out before and after the implementation of HBHCT programme in Bushenyi district of Uganda. A total of 1402 randomly selected adults (18 to 49 years) were interviewed in the baseline survey. After the implementation, a different set of randomly selected 1562 adults was interviewed using the same questionnaire. Data was collected on socio‐demographic characteristics, sexual behaviour, whether respondents had ever tested for HIV and stigma and discrimination towards HIV/AIDS.

Results

The proportion of people who had ever tested for HIV increased from 18.6% to 62% (p<0.001). Among people who had ever tested, the proportion of people who shared HIV test result with a sexual partner increased from 41% to 57% (p<0.001). The proportion of persons who wanted infection status of a family member not to be revealed decreased from 68% to 57% (p<0.001). Indicators of risk behaviour also improved; the proportion of people who exchanged money for sex reduced from 12% to 4% (p<0.001), who used a condom when money was exchanged during a sexual act increased from 39% to 80% (p<0.001) and who reported genital ulcer/discharge decreased from 22% to 10% (p<0.001).

Conclusion

These data suggest that HBHCT rapidly increased the uptake of HCT and may have led to reduction in high‐risk behaviours at population level as well as reduction in stigma and discrimination. Because HBCT programmes are cost‐effective, they should be considered for implementation in delivery of HIV services especially in areas where access to HCT is low.
Multivalent Porous Silicon Nanoparticles Enhance the Immune Activation Potency of Agonistic CD40 Antibody
Authors: Gu Luo , Ruff Laura E. , Qin Zhengtao , Corr Maripat , Hedrick Stephen M. , Sailor Michael J.
Published: June 2012

One of the fundamental paradigms in the use of nanoparticles to treat disease is to evade or suppress the immune system in order to minimize systemic side effects and deliver sufficient nanoparticle quantities to the intended tissues. However, the immune system is the body's most important and effective defense against diseases. It protects the host by identifying and eliminating foreign pathogens as well as self‐malignancies. Here we report a nanoparticle engineered to work with the immune system, enhancing the intended activation of antigen presenting cells (APCs). We show that luminescent porous silicon nanoparticles (LPSiNPs), each containing multiple copies of an agonistic antibody (FGK45) to the APC receptor CD40, greatly enhance activation of B cells. The cellular response to the nanoparticle‐based stimulators is equivalent to a 30–40 fold larger concentration of free FGK45. The intrinsic near‐infrared photoluminescence of LPSiNPs is used to monitor degradation and track the nanoparticles inside APCs.
A carbonium pseudo ionic liquid with excellent extractive desulfurization performance
Authors: Gao Jiajun , Meng Hong , Lu Yingzhou , Zhang Hongxing , Li Chunxi
Published: June 2012

Lewis hard acid AlCl3 was softened by some butyl halides forming highly polarized liquids. These liquids are similar to the ionic liquids (ILs) with metallic complex anion and varying composition, and thus termed here as carbonium pseudo ILs (CPILs). The CPILs, that is, t‐C4H9Cl‐AlCl3, n‐C4H9Cl‐AlCl3, and t‐C4H9Br‐AlCl3, show very strong desulfurization activity for various thiophenic compounds like 3‐methylthiophene, benzothiophene, and dibenzothiophene. The above thiophenic compounds can be removed completely from model oils within 20 min by a very small amount of CPILs reactive extractant. The extractive mechanism is deemed as an acid–base complexation along with alkylation of the thiophenic compounds, and the Lewis acidity comes from both carbonium ion (borderline acid) and the dissolved AlCl3 (hard acid). The t‐C4H9Cl‐AlCl3 shows good selectivity for three thiophenic compounds even in toluene‐containing system. Further, some CPILs show satisfactory desulfurization performance for the model gasoline that mimics the composition of real one. © 2012 American Institute of Chemical Engineers AIChE J, 59: 948–958, 2013
An algorithm to determine sample sizes for optimization with artificial neural networks
Authors: Nuchitprasittichai Aroonsri , Cremaschi Selen
Published: June 2012

This article presents an algorithm developed to determine the appropriate sample size for constructing accurate artificial neural networks as surrogate models in optimization problems. In the algorithm, two model evaluation methods—cross‐validation and/or bootstrapping—are used to estimate the performance of various networks constructed with different sample sizes. The optimization of a CO2 capture process with aqueous amines is used as the case study to illustrate the application of the algorithm. The output of the algorithm—the network constructed using the appropriate sample size—is used in a process synthesis optimization problem to test its accuracy. The results show that the model evaluation methods are successful in identifying the general trends of the underlying model and that objective function value of the optimum solution calculated using the surrogate model is within 1% of the actual value. © 2012 American Institute of Chemical Engineers AIChE J, 59: 805–812, 2013
Pattern formation during vasculogenesis
Authors: Czirok Andras , Little Charles D.
Published: June 2012

Vasculogenesis, the assembly of the first vascular network, is an intriguing developmental process that yields the first functional organ system of the embryo. In addition to being a fundamental part of embryonic development, vasculogenic processes also have medical importance. To explain the organizational principles behind vascular patterning, we must understand how morphogenesis of tissue level structures can be controlled through cell behavior patterns that, in turn, are determined by biochemical signal transduction processes. Mathematical analyses and computer simulations can help conceptualize how to bridge organizational levels and thus help in evaluating hypotheses regarding the formation of vascular networks. Here, we discuss the ideas that have been proposed to explain the formation of the first vascular pattern: cell motility guided by extracellular matrix alignment (contact guidance), chemotaxis guided by paracrine and autocrine morphogens, and sprouting guided by cell–cell contacts. Birth Defects Research (Part C) 96:153–162, 2012. © 2012 Wiley Periodicals, Inc.
New Ruthenium(II) Complexes Functionalized with Coumarin Derivatives: Synthesis, Energy‐Transfer‐Based Sensing of Esterase, Cytotoxicity, and Imaging Studies
Authors: Li Mei‐Jin , Wong Keith Man‐Chung , Yi Changqing , Yam Vivian Wing‐Wah
Published: June 2012

Two new bichromophoric ruthenium(II) complexes, [Ru(bpy)2(bpy‐CM)](PF6)2 and [Ru(bpy)2(bpy‐CM343)](PF6)2 (bpy=2,2′‐bipyridine, CM=coumarin) with appended coumarin ligands have been designed and synthesized. The energy‐transfer‐based sensing of esterase by the complexes has been studied by using UV/Vis and luminescence spectroscopic methods. The cytotoxicity and the cellular uptake of one of the complexes have also been investigated.
Reactivity of the 4,5‐Didehydroisoquinolinium Cation
Authors: Vinueza Nelson R. , Archibold Enada F. , Jankiewicz Bartłomiej J. , Gallardo Vanessa A. , Habicht Steven C. , Aqueel Mohammad Sabir , Nash John J. , Kenttämaa Hilkka I.
Published: June 2012

The chemical properties of a 1,8‐didehydronaphthalene derivative, the 4,5‐didehydroisoquinolinium cation, were examined in the gas phase in a dual‐cell Fourier‐transform ion cyclotron resonance (FT‐ICR) mass spectrometer. This is an interesting biradical because it has two radical sites in close proximity, yet their coupling is very weak. In fact, the biradical is calculated to have approximately degenerate singlet and triplet states. This biradical was found to exclusively undergo radical reactions, as opposed to other related biradicals with nearby radical sites. The first bond formation occurs at the radical site in the 4‐position, followed by that in the 5‐position. The proximity of the radical sites leads to reactions that have not been observed for related mono‐ or biradicals. Interestingly, some ortho‐benzynes have been found to yield similar products. Since ortho‐benzynes do not react via radical mechanisms, these products must be especially favorable thermodynamically.
Synthesis, Crystal Structures, and Properties of 6,12‐Diaryl‐Substituted Indeno[1,2‐b]fluorenes
Authors: Nishida Jun‐ichi , Tsukaguchi Shingo , Yamashita Yoshiro
Published: June 2012

Fused polycyclic indeno[1,2‐b]fluorene derivatives with aryl substituents at the 6,12‐positions have been prepared as a potential antiaromatic 20π electronic system. They showed strong absorptions in the visible region and amphoteric redox properties. The quinoid‐type molecular structures were revealed by X‐ray crystal‐structure analysis, which indicated that the bond lengths of the quinoid unit depend on the aryl substituents. Whereas nucleus‐independent chemical shift NICS(1) calculations indicate the antiaromatic nature of the s‐indacene core, they have higher stability than substituted acene derivatives. The derivatives with difluorophenyl or anthryl groups were stable in solution. Vapor‐deposited thin films showed ambipolar carrier transportation in the field‐effect transistor devices.
Full Exploration of the Diels–Alder Cycloaddition on Metallofullerenes M3N@C80 (M=Sc, Lu, Gd): The D5h versus Ih Isomer and the Influence of the Metal Cluster
Authors: Osuna Sílvia , Valencia Ramón , Rodríguez‐Fortea Antonio , Swart Marcel , Solà Miquel , Poblet Josep M.
Published: June 2012

In this work a detailed investigation of the exohedral reactivity of the most important and abundant endohedral metallofullerene (EMF) is provided, that is, Sc3N@Ih‐C80 and its D5h counterpart Sc3N@D5h‐C80, and the (bio)chemically relevant lutetium‐ and gadolinium‐based M3N@Ih/D5h‐C80 EMFs (M=Sc, Lu, Gd). In particular, we analyze the thermodynamics and kinetics of the Diels–Alder cycloaddition of s‐cis‐1,3‐butadiene on all the different bonds of the Ih‐C80 and D5h‐C80 cages and their endohedral derivatives. First, we discuss the thermodynamic and kinetic aspects of the cycloaddition reaction on the hollow fullerenes and the two isomers of Sc3N@C80. Afterwards, the effect of the nature of the metal nitride is analyzed in detail. In general, our BP86/TZP//BP86/DZP calculations indicate that [5,6] bonds are more reactive than [6,6] bonds for the two isomers. The [5,6] bond D5h‐b, which is the most similar to the unique [5,6] bond type in the icosahedral cage, Ih‐a, is the most reactive bond in M3N@D5h‐C80 regardless of M. Sc3N@C80 and Lu3N@C80 give similar results; the regioselectivity is, however, significantly reduced for the larger and more electropositive M=Gd, as previously found in similar metallofullerenes. Calculations also show that the D5h isomer is more reactive from the kinetic point of view than the Ih one in all cases which is in good agreement with experiments.
Soluble CD40 ligand (sCD40L) provides a new delivery system for targeted treatment
Authors: Kedar Rotem , Sabag Ofra , Licthenstein Michal , Lorberboum‐Galski Haya
Published: June 2012

BACKGROUND:

A wide range of hematologic malignancies arises from numerous cell types. In an attempt to offer a new target for treating B‐cell malignancies, in this study, the authors tested the possibility of using the CD40/CD40L system as a common targeting system for the various malignancies in this group.

METHODS:

Two chimeric proteins, soluble CD40 ligand (sCD40L)‐caspase 3 (sCD40L‐l‐Caspase3) and sCD40L‐pseudomonas exotoxin 38 (PE38) (sCD40L‐l‐PE38), were constructed, expressed, and partially purified. The ability of the chimeric proteins to kill tumor cells that expressed CD40 was tested by using proliferation assays. In addition, the induction of apoptosis in treated cells was followed by measuring expression levels of apoptotic proteins using real‐time polymerases chain reaction analysis, caspase 3 enzymatic activity, and tracking changes in the cell cycle with fluorescence‐activated cell‐sorting analysis.

RESULTS:

The chimeric proteins exhibited concentration‐dependent and time‐dependent killing ability. The new chimeric proteins had no effect in several carcinoma cell lines that did not express the CD40 receptor. Treating tumor cells with sCD40L‐based chimeric proteins led to internalization of the fusion proteins into the cell cytoplasm of B cells. Shortly after treatment, a sharp rise in B‐cell chronic lymphocytic leukemia/lymphoma 2 (Bcl2) expression levels occurred. Approximately 36 hours after the initiation of treatment, Bcl2 levels dropped, whereas Bcl2‐associated X protein (Bax) expression levels rose, pushing the cells toward apoptosis. Concomitantly, caspase 3 RNA levels rose.

CONCLUSIONS:

sCD40L‐based chimeric proteins were able to bind and internalize into B cells that expressed the CD40 receptor and specifically and efficiently induced apoptotic death. Moreover, the current results validated for the first time the ability of sCD40L to serve as a direct delivery system for targeted molecules. sCD40L‐based chimeric cytotoxic proteins offer a new weapon in the everlasting war against cancer. Cancer 2012. © 2012 American Cancer Society.
Adherence to practice guidelines for atypical glandular cells on cervical cytology
Authors: Sharpless Kathryn E. , King Cara R. , Schnatz Peter F.
Published: June 2012

BACKGROUND:

Atypical glandular cells (AGC) on cervical cytology are high–risk, requiring an extensive evaluation. Compliance with practice guidelines for AGC, however, has been low. Some AGC cytology reports contain cytopathologist recommendations for evaluation. This study determines whether evaluation rates for AGC have improved over time, and whether cytopathologists' recommendations correlate with the types of evaluation women receive.

METHODS:

Evaluation rates from 284 women with AGC (2004‐2007) were compared with findings from 1998‐2001. Rates of evaluations were compared based on cytology report recommendations.

RESULTS:

A total of 76.1% of the AGC cases had histologic sampling, and 58.8% had a comprehensive evaluation. These rates are higher than those from 1998‐2001 (63.5% and 35.8%, respectively; P<.01). Rates of evaluations of women with AGC “favor neoplasia” did not increase between the 2 time periods. Between 2004‐2005 and 2006‐2007, rates of comprehensive initial evaluations and endometrial sampling in women ≥35 years of age did not increase. Of the AGC reports that did contain cytopathologist recommendations, 28% were consistent with practice guidelines, 26% recommended an incomplete histologic evaluation, and 46% recommended repeat cytology. Women whose AGC report recommended a comprehensive evaluation or any histologic evaluation were more likely to have a comprehensive work–up (79%) than those whose reports did not contain recommendations (55%, P <0.01) or recommended repeat cytology (51%, P<0.02).

CONCLUSIONS:

Adherence to practice guidelines for the evaluation of women with AGC has improved but continues to be suboptimal. Our findings suggest that continuing education and including practice guidelines on AGC cytology reports may improve compliance. Cancer (Cancer Cytopathol) 2013;121:47–53 © 2012 American Cancer Society.
Disordered eating following exposure to television and internet coverage of the March 2011 japan earthquake
Authors: Rodgers Rachel F. , Franko Debra L. , Brunet Alain , Herbert Christophe F. , Bui Eric
Published: June 2012

Objective:

To prospectively explore the relationship between exposure to potentially distressing news content and disordered eating.

Method:

Within 2 weeks of the March 3, 2011 Japan earthquake, an online survey was conducted among non‐Japanese adults in distant countries (N = 698) assessing time spent on TV and the internet watching the news as well as peritraumatic reactions to the news and sleep disturbance. Participants were invited to complete a followup survey two months later [n = 113, mean age (SD) = 38.8 (11.91), 73% female] reporting on eating disorder symptoms.

Results:

Exposure to TV and, to a lesser extent, internet coverage of the Japan disaster were associated with disordered eating, in particular dieting and oral control, as measured by the eating attitudes test. Peritraumatic reactions and sleep disturbance displayed specific patterns of association with disordered eating.

Discussion:

Exposure to media coverage of distant disasters may be associated with increased disordered eating. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012;45:845–849)
Applications of NMR metabolomics to the study of foodstuffs: Truffle, kiwifruit, lettuce, and sea bass
Authors: Mannina Luisa , Sobolev Anatoly P. , Capitani Donatella
Published: June 2012

In this review, four examples of the NMR metabolomic approach to foodstuff investigation are reported. Different types of foodstuff of different origin (namely truffle, kiwifruit, lettuce, and sea bass), with different metabolite composition, processing, and storage procedures have been chosen to demonstrate the versatility and potentiality of NMR in the foodstuff analysis. Fundamental aspects of NMR methodology such as sample preparation, metabolites extraction, quantitative elaboration of spectral data, and statistical analysis have been described. Metabolic profilings of aqueous and/or organic extracts as obtained by one‐ and two‐dimensional NMR experiments have been reported together with the results obtained from their statistical elaboration. Discrimination between wild and farmed sea bass and between genetically modified and wild lettuces as well as changes in the kiwifruit metabolic profiles monitored over the season have been investigated. For each foodstuff, some complementary findings provided by other analytical methods are also described to underline the importance of different analytical approaches to explore specific aspects related to foodstuff.
Nutritional genomics for the characterization of the effect of bioactive molecules in lipid metabolism and related pathways
Authors: Daimiel Lidia , Vargas Teodoro , Ramírez de Molina Ana
Published: June 2012

Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Thus, investigators have focused their efforts on gaining insight into understanding the mechanisms involved in the development and evolution of these diseases. In the past decade, and with the contribution of the ‐omics technologies, strong evidence has supported an essential role of gene–nutrient interactions in these processes, pointing at natural bioactive molecules as promising complementary agents that are useful in preventing or mitigating these diseases. In addition, alterations in lipid metabolism have recently gained strong interest since they have been described as a common event required for the progression of both diseases. In the present review, we give an overview of lipid metabolism, mainly focusing on lipoprotein metabolism and the mechanisms controlling lipid homeostasis. In addition, we review the modulation of lipid metabolism by bioactive molecules, highlighting their potential use as therapeutic agents in preventing, and treating chronic diseases such as cardiovascular disease and cancer. Finally, we report the usefulness of the ‐omics technologies in nutritional research, focusing on recent findings, within nutritional genomics, in the interaction of bioactive components from foods with several genes that are involved in the development and progression of these diseases.
The role of CXCR3 and CXCR4 in colorectal cancer metastasis
Authors: Murakami Teppei , Kawada Kenji , Iwamoto Masayoshi , Akagami Masatoshi , Hida Koya , Nakanishi Yuki , Kanda Keitaro , Kawada Mayumi , Seno Hiroshi , Taketo Makoto Mark , Sakai Yoshiharu
Published: June 2012

Chemokines and their receptors play key roles in leukocyte trafficking and are also implicated in cancer metastasis. We previously demonstrated that forced expression of CXCR3 promotes colon cancer metastasis preferentially to the draining lymph nodes (LNs), with poor prognosis. Using clinical colorectal cancer (CRC) samples, here, we show that expressions of CXCR3 and CXCR4 are significantly higher in metastatic foci within LNs and liver compared to primary tumors, whereas ligands for CXCR3 and CXCR4 are not. We also have demonstrated that some human CRC cell lines constitutively express both CXCR3 and CXCR4, and that activation of CXCR3 strengthens the CXCR4‐mediated cell migration in vitro in a synergistic manner. By constructing SW620 cell lines with reduced expression of CXCR3 and/or CXCR4 using microRNA, we investigated in vivo metastatic activities in a mouse rectal transplantation model. Six weeks after inoculation, CXCR3‐, CXCR4‐, and CXCR3/CXCR4 double‐knockdowns significantly reduced metastasis to LNs, liver and lungs, compared to the control (p < 0.05). Importantly, its suppressive effect on LN metastasis was significantly stronger in CXCR3‐ and CXCR3/CXCR4 double‐knockdowns. In addition, CXCR3‐ and CXCR3/CXCR4 double‐knockdowns significantly decreased the dissemination of cancer cells to liver and lungs, even after 2 weeks. These results indicate that targeting CXCR3 and CXCR4 can be a promising therapy against CRC metastasis.
Fibrin chain cross‐linking, fibrinolysis, and in vivo sealing efficacy of differently structured fibrin sealants
Authors: Hedrich Hans Christian , Simunek Manuela , Reisinger Sonja , Ferguson James , Gulle Heinz , Goppelt Andreas , Redl Heinz
Published: June 2012

In this study, we compared the sealing characteristics and efficacy of a fibrin sealant with reduced plasminogen (FS‐rplg) and a fibrin sealant with aprotinin as a fibrinolysis inhibitor (FS‐apr). The relevant sealing characteristics including clot structure, fibrin chain cross‐linking, and clot lysis were tested in the laboratory. The sealing efficacy was then investigated in a follow‐up animal model to determine differences in the in vivo sealing properties. A total of 46 animals were available for the final analysis with 23 animals in each treatment arm. In conclusion, we saw differences in vitro between FS‐rplg and FS‐apr in ultrastructure and α‐chain cross‐linking rates as well as in the rate of fibrinolysis. These differences may explain the significantly enhanced sealing efficacy in FS‐apr compared to FS‐rplg shown in vivo in a rabbit intestinal model. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 1507–1512, 2012.
Synthesis and characterization of Mg‐Ca‐Sr alloys for biodegradable orthopedic implant applications
Authors: Berglund Ida S. , Brar Harpreet S. , Dolgova Natalia , Acharya Abhinav P. , Keselowsky Benjamin G. , Sarntinoranont Malisa , Manuel Michele V.
Published: June 2012

Magnesium has recently received an increased amount of interest due to its potential use in biodegradable implant applications. The rapid degradation of conventional Mg is, however, a major limitation that needs to be addressed in the design of these materials, along with consideration of toxicity in selection of alloying elements. In this study, five alloys in the Mg‐xCa‐ySr system (x= 0.5–7.0 wt %;y= 0.5–3.5 wt %) were prepared and characterized for their suitability as degradable orthopedic implant materials. The alloys were characterized using optical microscopy, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, X‐ray diffraction, degradation measurements in Hanks' solution at 37°C, compression testing, andin vitrocytotoxicity testing with a mouse osteoblastic cell line. The results indicate that the Mg‐1.0Ca‐0.5Sr alloy is the most promising alloy for orthopedic implant applications since it showed the lowest degradation rate in Hanks' solution (0.01 mL cm−2h−1) along with no significant toxicity to MC3T3‐E1 osteoblasts and a compressive strength of 274 ± 4 MPa. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 1524–1534, 2012.
Microstructure and biological properties of micro‐arc oxidation coatings on ZK60 magnesium alloy
Authors: Pan Y. K. , Chen C. Z. , Wang D. G. , Yu X.
Published: June 2012

Ceramic coatings were prepared on ZK60 magnesium alloy in electrolyte with different concentration ratio of calcium and phosphorus (Ca/P) by micro‐arc oxidation (MAO) technique at constant voltage. The microstructure, phase composition, elemental distribution, corrosion resistance, and adhesion of the coatings were investigated by scanning electron microscope (SEM), X‐ray diffractometer (XRD), energy‐dispersive X‐ray spectrometry (EDS), electrochemical workstation, and scratch spectrometer, respectively. The coating biocompatibility was evaluated by in vitro cytotoxicity tests and systemic toxicity tests, and the bioactivity and degradability were evaluated by simulation body fluid (SBF) immersion tests. SEM shows that pores with different shapes distribute all over the coating surface. The adhesion and thickness of the coatings increases with increasing Ca/P ratio of electrolyte. The in vitro cytotoxicity tests and systemic toxicity texts demonstrate that the coatings have no toxicity to cell and living animal, which show that the coatings have excellent biocompatibility. XRD analysis shows that bioactive calciumphosphate (CaP) phases such as hydroxyapatite (HA, Ca10(PO4)6(OH)2) and calcium pyrophosphate (CPP, Ca2P2O7) are induced in the immersed coatings, indicating that the MAO coatings have excellent bioactivity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 1574–1586, 2012.
Vitamin K, vertebral fractures, vascular calcifications, and mortality: VItamin K Italian (VIKI) dialysis study
Authors: Fusaro Maria , Noale Marianna , Viola Valentina , Galli Francesco , Tripepi Giovanni , Vajente Nicola , Plebani Mario , Zaninotto Martina , Guglielmi Giuseppe , Miotto Diego , Dalle Carbonare Luca , D'Angelo Angela , Naso Agostino , Grimaldi Cristina , Miozzo Davide , Giannini Sandro , Gallieni Maurizio ,   for the VItamin K Italian (VIKI) Dialysis Study Investigators
Published: June 2012

Vitamin K (vitamin K1 or phylloquinone and vitamin K2, a series of menaquinones [MKs]) is involved in the production of bone and matrix amino acid γ-carboxy-glutamic acid (Gla) proteins, regulating bone and vascular calcification. Low vitamin K concentrations are associated with increased risks of fractures and vascular calcification, and frequent complications in hemodialysis patients. We carried out an observational study to establish the prevalence of vitamin K deficiency and to assess the relationship between vitamin K status, vertebral fractures, vascular calcification, and survival in 387 patients on hemodialysis for ≥1 year. We determined plasma levels of vitamin K compound, bone-Gla-protein, matrix-Gla-protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by ≥20%) and aortic and iliac calcifications were also investigated in a spine (D5–L4) radiograph. Three-year patient survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%), and MK4 (14.5%). A total of 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification, and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest predictor of vertebral fractures (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.38–6.26). MK4 deficiency was a predictor of aortic calcification (OR, 2.82; 95% CI, 1.14–7.01), whereas MK5 deficiency actually protected against it (OR, 0.38; 95% CI, 0.15–0.95). MK7 deficiency was a predictor of iliac calcification (OR, 1.64; 95% CI, 1.03–2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR, 1.76; 95% CI, 1.00–3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, and cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification. © 2012 American Society for Bone and Mineral Research.
Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: A study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry
Authors: Khan Aneal , Hangartner Thomas , Weinreb Neal J , Taylor John S , Mistry Pramod K
Published: June 2012

We hypothesized that overall disease activity or the severity of involvement of individual disease compartments, as measured by clinical and surrogate markers, predict the risk of avascular osteonecrosis (AVN) or fractures in type 1 Gaucher disease (GD1). We applied our risk-set matched case-control method to identify four patient groups within the International Collaborative Gaucher Group (ICGG) Gaucher Registry based on the presence and absence of AVN and fractures. Characteristics of GD1 were examined by comparing the distributions of each risk factor in cases versus matched controls using conditional logistic regression to calculate adjusted odds ratios (OR). Potential risk factors included hematological and visceral parameters, GD1 biomarkers, white blood cells, GBA1 genotype, and spine and femur dual-energy X-ray absorptiometry (DXA) Z-scores. In the total population of 5894 ICGG Gaucher Registry patients, 544 experienced at least one episode of AVN; 2008 reported no history of AVN. Clinical and surrogate markers of disease activity were similar in patients with and without AVN; patients with AVN were 1.6 times more likely to be anemic compared to matched controls (OR = 1.59; 95% confidence interval [CI], 1.06–2.38, p < 0.05). For fractures, 319 patients suffered fractures and 1233 had no prior history of fractures. Clinical and surrogate markers of disease in patients with and without fractures were similar, except for mean lumbar spine DXA Z-scores. Among patients with fractures, 49.3% had DXA Z-scores ≤ −1 compared to 31.0% in the control group. Compared to controls with Z-scores > −1.0, GD1 patients exhibiting Z-scores ≤ −1 had an OR of 5.55 (95% CI, 1.81–17.02, p < 0.01) for fracture. In GD1, after controlling for gender, year of birth, treatment status, and splenectomy status, we identified new risk factors for AVN and fractures. Concurrent anemia was associated with an increased risk for AVN. Low bone mineral density of the lumbar spine was a strong risk factor for fractures of the spine and femur in GD1. © 2012 American Society for Bone and Mineral Research.
A controlled register-based study of 460 neurofibromatosis 1 patients: Increased fracture risk in children and adults over 41 years of age
Authors: Heervä Eetu , Koffert Anna , Jokinen Elina , Kuorilehto Tommi , Peltonen Sirkku , Aro Hannu T , Peltonen Juha
Published: June 2012

Neurofibromatosis 1 (NF1, von Recklinghausen's disease) is an autosomal dominant neurocutaneous-skeletal syndrome in which low bone mineral density (BMD) and osteoporosis are common. Low BMD is, however, not the sole component of fracture risk. In the current study, 460 Finnish patients with NF1 were identified from the hospital medical records and their fracture risk was evaluated. The control population included 3988 appendectomy patients whose age and gender distribution was similar to that of the NF1 patients. Medical records of NF1 and control cohorts were screened for fractures according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) between January 2000 and October 2011. The results show that patients with NF1 had increased age-dependent fracture risk compared to controls. Specifically, patients with NF1 aged 41 years and older had a risk ratio of ×5.2 for fractures compared to controls, and children with NF1 had a ×3.4 risk ratio for fractures compared to children without NF1. In contrast, the fracture risk was not increased in NF1 patients aged 17 to 40 years. When fractures not traditionally related to osteoporosis such as fractures of fingers, toes, and skull were excluded, the results were essentially the same. No gender related differences were observed. In conclusion, patients with NF1 have increased fracture risk depending on age. We recommend considering prophylactic measures, such as lifestyle advice, to prevent fractures from occurring. © 2012 American Society for Bone and Mineral Research.