bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of immunity-supported senescence enhances susceptibility to hepatocellular carcinogenesis and progression in Toll-like receptor 2-deficient mice
Authors: Lin Heng , Yan Jun , Wang Ziyan , Hua Fang , Yu Jiaojiao , Sun Wei , Li Ke , Liu Hong , Yang Hongzhen , Lv Qi , Xue Jianfei , Hu Zhuo-Wei
Published: August 2012

Hepatocellular carcinoma (HCC) is a complication at the endstage of chronic inflammatory liver diseases with dismal prognosis. Targeting of Toll-like receptor (TLR) 2 attenuates tumor metastases; we hypothesized that blocking TLR2 might also play a crucial role in reducing hepatocarcinogenesis. Surprisingly, we found that the genetic deletion of TLR2 increased susceptibility to diethylnitrosamine (DEN), a genotoxic carcinogen that can induce HCC. Indeed, TLR2-deficient mice showed a significant increase in carcinogenesis and progression of HCC as indicated by increases in tumor nodule size, tumor volume, and animal death. The enhanced susceptibility to DEN-induced HCC was associated with a broad-spectrum reduction in the immune response to DEN-induced liver injury. We found that TLR2 deficiency caused a decrease in the infiltration of macrophages and an attenuation of apoptosis signal regulating kinase 1 (ASK1) / p38 mitogen-activated protein kinase (p38 MAPK) / nuclear factor kappa B (NF-κB) signaling, which led to a decrease in the expression of interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1α/β, IL-6, and Cxcl-2 as well as suppression of autophagy flux and increases in oxidative stress and p62 aggregation in liver tissue. The defects in immune networks resulted in suppressed p21- and p16/pRb-dependent senescence, which caused an increase in proliferation and a decrease in apoptotic and autophagy-associated cell death in mouse livers. Restoring cellular senescence and autophagy flux by treating TLR2-deficient mice with IFN-γ, a T helper 1 (Th1) cytokine and positive modulator of senescence and autophagy, could attenuate the carcinogenesis and progression of HCC associated with TLR2-deficient animals. Conclusion: The loss of immune networks supporting cellular senescence and autophagy flux is attributed to enhanced susceptibility to DEN-induced hepatocellular carcinogenesis and progression in TLR2-deficient mice. These findings may be used to prevent the development of liver cancer. (Hepatology 2013)
α5β1-integrins are sensors for tauroursodeoxycholic acid in hepatocytes
Authors: Gohlke Holger , Schmitz Birte , Sommerfeld Annika , Reinehr Roland , Häussinger Dieter
Published: August 2012

Ursodeoxycholic acid, which

in vivo

is converted to its taurine conjugate tauroursodeoxycholic acid (TUDC), is a mainstay for the treatment of cholestatic liver disease. Earlier work showed that TUDC exerts its choleretic properties in the perfused rat liver in an α5β1 integrin-mediated way. However, the molecular basis of TUDC-sensing in the liver is unknown. We herein show that TUDC (20 μmol/L) induces in perfused rat liver and human HepG2 cells the rapid appearance of the active conformation of the β1 subunit of α5β1 integrins, followed by an activating phosphorylation of extracellular signal-regulated kinases. TUDC-induced kinase activation was no longer observed after β1 integrin knockdown in isolated rat hepatocytes or in the presence of an integrin-antagonistic hexapeptide in perfused rat liver. TUDC-induced β1 integrin activation occurred predominantly inside the hepatocyte and required TUDC uptake by way of the Na+/taurocholate cotransporting peptide. Molecular dynamics simulations of a 3D model of α5β1 integrin with TUDC bound revealed significant conformational changes within the head region that have been linked to integrin activation before.

Conclusions:

TUDC can directly activate intrahepatocytic β1 integrins, which trigger signal transduction pathways toward choleresis. (Hepatology 2013)
Diffusion of new technology, health services and information after a crisis: a focus group study of the Sichuan “5.12” Earthquake
Authors: Zhou Hong , Shi Lu , Mao Yuping , Tang Juan , Zeng Yu
Published: August 2012

Introduction

The Sichuan “5.12” Earthquake in 2008 occurred in a relatively underdeveloped area in China. The rainy weather, the mountainous environment and the local languages all posed major challenges to the dissemination of information and services after the disaster. By adopting a communication perspective, this study applies the diffusion of innovations theory to investigate how healthcare professionals diffused health technologies, health information and services during the rescue and relief operation.

Method

The authors conducted three focus group sessions with the health professionals who had attended to the rescue and relief work of the Sichuan “5.12” Earthquake in 2008. A range of questions regarding the diffusion of innovations were asked during these sessions.

Results

The health professionals used their cell phones to communicate with other healthcare providers, disseminated knowledge of health risks and injuries to affected residents with pamphlets and posters and attended daily meetings at the local government offices. They reported on the shortage of maritime satellite cell phones and large‐size tents for medical use, and the absence of fully equipped ambulances. Volunteers, local health professionals and local officials provided health information and services in different ways. However, the diffusion of health information and services was less likely to reach those living next to transportation centers, in remote areas and in disaster areas neglected by the media.

Discussion

New communication devices such as cell phones and the mobile Internet enabled medical professionals to coordinate the rescue and relief work after this major natural disaster, at a time when the country's emergency response system still had plenty of room for improvement. In future, the mobile Internet should be used as a means of collecting bottom‐up disaster reports so that the media will not neglect any disaster areas as they did during the Sichuan Earthquake. Rescue relief work would have been substantially easier if medical teams had been equipped with advanced appliances such as maritime satellite cell phones. “Disaster medicine” should be treated as a separate discipline in medical schools and receive more investment. Moreover, a stronger public health emergency response system is needed for more efficient dispatch and coordination. Copyright © 2012 John Wiley & Sons, Ltd.
An association between clock genes and clock‐controlled cell cycle genes in murine colorectal tumors
Authors: Soták Matúš , Polidarová Lenka , Ergang Peter , Sumová Alena , Pácha Jiří
Published: August 2012

Disruption of circadian machinery appears to be associated with the acceleration of tumor development. To evaluate the function of the circadian clock during neoplastic transformation, the daily profiles of the core clock genes Per1, Per2, Rev‐Erbα and Bmal1, the clock‐controlled gene Dbp and the clock‐controlled cell cycle genes Wee1, c‐Myc and p21 were detected by real‐time RT‐PCR in chemically induced primary colorectal tumors, the surrounding normal tissue and in the liver. The circadian rhythmicity of Per1, Per2, Rev‐Erbα and Dbp was significantly reduced in tumor compared with healthy colon and the rhythmicity of Bmal1 was completely abolished. Interestingly, the circadian expression of Per1, Per2, Rev‐Erbα and Dbp persisted in the colonic tissue surrounding the tumor but the rhythmic expression of Bmal1 was also abolished. Daily profiles of Wee1, c‐Myc and p21 did not exhibit any rhythmicity either in tumors or in the colon of healthy animals. The absence of diurnal rhythmicity of cell cycle genes was partially associated with ageing, because young healthy mice showed rhythmicity in the core clock genes as well as in the Wee1 and p21. In the liver of tumor‐bearing mice the clock gene rhythms were temporally shifted. The data suggest that the circadian regulation is distorted in colonic neoplastic tissue and that the gene‐specific disruption may be also observed in the non‐neoplastic tissues. These findings reinforce the role of peripheral circadian clockwork disruption for carcinogenesis and tumor progression.
Role of GRB2‐associated binder 1 in epidermal growth factor receptor‐induced signaling in head and neck squamous cell carcinoma
Authors: Hoeben A. , Martin D. , Clement P.M. , Cools J. , Gutkind J.S.
Published: August 2012

The epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Despite the high expression of EGFR in HNSCC, EGFR inhibitors have only limited success as monotherapy. The Grb2‐associated binder (GAB) family of adaptor proteins acts as docking/scaffolding molecules downstream of tyrosine kinase receptors. We hypothesized that GAB1 may amplify EGFR‐induced signaling in HNSCCs and therefore could play a role in the reduced sensitivity of HNSCC to EGFR inhibitors. We used representative human HNSCC cell lines overexpressing wild type EGFR, and expressing GAB1 but not GAB2. We demonstrated that baseline Akt and MAPK signaling were reduced in HNSCC cells in which GAB1 expression was reduced. Furthermore, the maximal EGF‐induced activation of the Akt and MAPK pathway was reduced and delayed, and the duration of the EGF‐induced activation of these pathways was reduced in cells with GAB1 knock‐down. In agreement with this, HNSCC cells in which GAB1 levels were reduced showed an increased sensitivity to the EGFR inhibitor gefitinib. Our work demonstrates that GAB1 plays an important role as part of the mechanism of by which EGFR induces induced activation of the MAPK and AKT pathway. Our results identify GAB1 as an amplifier of the EGFR‐initiated signaling, which may also interfere with EGFR degradation. These findings support the emerging notion that reducing GAB1 function may sensitize HNSCC to EGFR inhibitors, hence representing a new therapeutic target HNSCC treatment in combination with EGFR targeting agents.
P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury
Authors: Ito G. , Suekawa Y. , Watanabe M. , Takahashi K. , Inubushi T. , Murasaki K. , Hirose N. , Hiyama S. , Uchida T. , Tanne K.
Published: August 2012

Background

The present study directly addresses the roles of the P2X7 receptor (P2X7R), an ionotropic adenosine triphosphate (ATP) receptor, and cytokines in the induction of orofacial pain following chronic constriction injury (CCI) of the infraorbital nerve (IoN).

Methods

Rats were anesthetized, and ligatures of 4‐0 chromic gut were tied around the IoN. A438079, a P2X7R antagonist or SB203580, a phosphorylated (p)‐p38 mitogen‐activated protein kinase (MAPK) inhibitor, was infused intrathecally into CCI‐treated rats. In another group of rats, 3′‐O‐(4‐benzoylbenzoyl) adenosine 5′‐triphosphate (BzATP), a P2X7R agonist, was infused intrathecally with A438079, SB203580 or etanercept, a tumor necrosis factor (TNF)‐α receptor‐binding recombinant drug.

Results

CCI of the IoN induced tactile allodynia/hyperalgesia and up‐regulation of P2X7R, membrane‐bound TNF‐α (mTNF‐α) and soluble TNF‐α (sTNF‐α) in the trigeminal sensory nuclear complex (TNC). Tactile allodynia/hyperalgesia or up‐regulation of mTNF‐α and sTNF‐α in the TNC following CCI of the IoN was inhibited by A438079. SB203580 also attenuated tactile allodynia/hyperalgesia or up‐regulation of mTNF‐α, but not the up‐regulation of sTNF‐α in the TNC. Treatment of rats with BzATP induced tactile allodynia/hyperalgesia and up‐regulation of sTNF‐α and p‐p38 in the TNC. Tactile allodynia/hyperalgesia or up‐regulation of sTNF‐α following BzATP treatment was inhibited by SB203580 and etanercept.

Conclusions

Based on these findings, phosphorylation of p38 MAPK via P2X7R may induce tactile allodynia/hyperalgesia, which is most likely mediated by sTNF‐α released by microglia.
Multi‐site pain and working conditions as predictors of work ability in a 4‐year follow‐up among food industry employees
Authors: Neupane S. , Virtanen P. , Leino‐Arjas P. , Miranda H. , Siukola A. , Nygård C.‐H.
Published: August 2012

Background

We investigated the separate and joint effects of multi‐site musculoskeletal pain and physical and psychosocial exposures at work on future work ability.

Methods

A survey was conducted among employees of a Finnish food industry company in 2005 (n = 1201) and a follow‐up survey in 2009 (n = 734). Information on self‐assessed work ability (current work ability on a scale from 0 to 10; 7 = poor work ability), multi‐site musculoskeletal pain (pain in at least two anatomical areas of four), leisure‐time physical activity, body mass index and physical and psychosocial exposures was obtained by questionnaire. The separate and joint effects of multi‐site pain and work exposures on work ability at follow‐up, among subjects with good work ability at baseline, were assessed by logistic regression, and p‐values for the interaction derived.

Results

Compared with subjects with neither multi‐site pain nor adverse work exposure, multi‐site pain at baseline increased the risk of poor work ability at follow‐up, allowing for age, gender, occupational class, body mass index and leisure‐time physical activity. The separate effects of the work exposures on work ability were somewhat smaller than those of multi‐site pain. Multi‐site pain had an interactive effect with work environment and awkward postures, such that no association of multi‐site pain with poor work ability was seen when work environment was poor or awkward postures present.

Conclusions

The decline in work ability connected with multi‐site pain was not increased by exposure to adverse physical or psychosocial factors at work.
Wrapping and dispersion of multiwalled carbon nanotubes improves electrical conductivity of protein–nanotube composite biomaterials
Authors: Voge Christopher M. , Johns Jeremy , Raghavan Mekhala , Morris Michael D. , Stegemann Jan P.
Published: August 2012

Composites of extracellular matrix proteins reinforced with carbon nanotubes have the potential to be used as conductive biopolymers in a variety of biomaterial applications. In this study, the effect of functionalization and polymer wrapping on the dispersion of multiwalled carbon nanotubes (MWCNT) in aqueous media was examined. Carboxylated MWCNT were wrapped in either Pluronic® F127 or gelatin. Raman spectroscopy and X‐ray photoelectron spectroscopy showed that covalent functionalization of the pristine nanotubes disrupted the carbon lattice and added carboxyl groups. Polymer and gelatin wrapping resulted in increased surface adsorbed oxygen and nitrogen, respectively. Wrapping also markedly increased the stability of MWCNT suspensions in water as measured by settling time and zeta potential, with Pluronic®‐wrapped nanotubes showing the greatest effect. Treated MWCNT were used to make 3D collagen–fibrin–MWCNT composite materials. Carboxylated MWCNT resulted in a decrease in construct impedance by an order of magnitude, and wrapping with Pluronic® resulted in a further order of magnitude decrease. Functionalization and wrapping also were associated with maintenance of fibroblast function within protein–MWCNT materials. These data show that increased dispersion of nanotubes in protein–MWCNT composites leads to higher conductivity and improved cytocompatibility. Understanding how nanotubes interact with biological systems is important in enabling the development of new biomedical technologies. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:231–238, 2013.
Self‐assembled smooth muscle cell tissue rings exhibit greater tensile strength than cell‐seeded fibrin or collagen gel rings
Authors: Adebayo Olufunmilayo , Hookway Tracy A. , Hu Jason Z. , Billiar Kristen L. , Rolle Marsha W.
Published: August 2012

In this study, we created self‐assembled smooth muscle cell (SMC) tissue rings (comprised entirely of cells and cell‐derived matrix; CDM) and compared their structure and material properties with tissue rings created from SMC‐seeded fibrin or collagen gels. All tissue rings were cultured statically for 7 days in supplemented growth medium (with ε‐amino caproic acid, ascorbic acid, and insulin‐transferrin‐selenium), prior to uniaxial tensile testing and histology. Self‐assembled CDM rings exhibited ultimate tensile strength and stiffness values that were two‐fold higher than fibrin gel and collagen gel rings. Tensile testing of CDM, fibrin gel and collagen gel rings treated with deionized water to lyse cells showed little to no change in mechanical properties relative to untreated ring samples, indicating that the ECM dominates the measured ring mechanics. In addition, CDM rings cultured in supplemented growth medium were significantly stronger than CDM rings cultured in standard, unsupplemented growth medium. These results illustrate the potential utility of self‐assembled cell rings as model CDM constructs for tissue engineering and biomechanical analysis of ECM material properties. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Silk fibroin particles as templates for mineralization of calcium‐deficient hydroxyapatite
Authors: Choi Youngeun , Cho Se Youn , Park Doo Jin , Park Hyun Ho , Heo Semi , Jin Hyoung‐Joon
Published: August 2012

Silk fibroin particles prepared by phase separation with polyethylene oxide were coated with calcium‐deficient hydroxyapatite (CDHA) crystals under various pH conditions. For different pH values, the growth and the morphology of CDHA crystals on the surface of silk fibroin particles were investigated in detail by zeta potential analysis, scanning electron microscopy, transmission electron microscopy, and X‐ray diffraction techniques. Negative charges formed by deprotonation of the functional groups on the surface of silk fibroin particles at high pH lead to an increase of binding affinity between the calcium ions of the CDHA crystals and the functional groups of the silk fibroin particles. Consequently, the generation of many CDHA crystals was promoted to deposit on the surface of silk fibroin particles at a high pH value. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
The R740S mutation in the V-ATPase a3 subunit increases lysosomal pH, impairs NFATc1 translocation, and decreases in vitro osteoclastogenesis
Authors: Voronov Irina , Ochotny Noelle , Jaumouillé Valentin , Owen Celeste , Manolson Morris F , Aubin Jane E
Published: August 2012

Vacuolar H+-ATPase (V-ATPase), a multisubunit enzyme located at the ruffled border and in lysosomes of osteoclasts, is necessary for bone resorption. We previously showed that heterozygous mice with an R740S mutation in the a3 subunit of V-ATPase (+/R740S) have mild osteopetrosis resulting from an ∼90% reduction in proton translocation across osteoclast membranes. Here we show that lysosomal pH is also higher in +/R740S compared with wild-type (+/+) osteoclasts. Both osteoclast number and size were decreased in cultures of +/R740S compared with +/+ bone marrow cells, with concomitant decreased expression of key osteoclast markers (TRAP, cathepsin K, OSCAR, DC-STAMP, and NFATc1), suggesting that low lysosomal pH plays an important role in osteoclastogenesis. To elucidate the molecular mechanism of this inhibition, NFATc1 activation was assessed. NFATc1 nuclear translocation was significantly reduced in +/R740S compared with +/+ cells; however, this was not because of impaired enzymatic activity of calcineurin, the phosphatase responsible for NFATc1 dephosphorylation. Protein and RNA expression levels of regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of NFATc1 activation and a protein degraded in lysosomes, were not significantly different between +/R740S and +/+ osteoclasts, but the RCAN1/NFATc1 ratio was significantly higher in +/R740S versus +/+ cells. The lysosomal inhibitor chloroquine significantly increased RCAN1 accumulation in +/+ cells, consistent with the hypothesis that higher lysosomal pH impairs RCAN1 degradation, leading to a higher RCAN1/NFATc1 ratio and consequently NFATc1 inhibition. Our data indicate that increased lysosomal pH in osteoclasts leads to decreased NFATc1 signaling and nuclear translocation, resulting in a cell autonomous impairment of osteoclastogenesis in vitro. © 2013 American Society for Bone and Mineral Research
Electronic fluxes during diels‐alder reactions involving 1,2‐benzoquinones: mechanistic insights from the analysis of electron localization function and catastrophe theory
Authors: González‐Navarrete Patricio , Domingo Luis R. , Andrés Juan , Berski Slawomir , Silvi Bernard
Published: August 2012

By means of the joint use of electron localization function (ELF) and Thom's catastrophe theory, a theoretical analysis of the energy profile for the hetero‐Diels‐Alder reaction of 4‐methoxy‐1,2‐benzoquinone1and methoxyethylene2has been carried out. The 12 different structural stability domains obtained by the bonding evolution theory have been identified as well as the bifurcation catastrophes (fold and cusp) responsible for the changes in the topology of the system. This analysis permits finding a relationship between the ELF topology and the evolution of the bond breaking/forming processes and electron pair rearrangements through the reaction progress in terms of the different ways of pairing up the electrons. The reaction mechanism corresponds to an asynchronous electronic flux; first, the O1C5 bond is formed by the nucleophilic attack of the C5 carbon of the electron rich ethylene2on the most electrophilically activated carbonyl O1 oxygen of1, and once the σ bond has been completed, the formation process of the second O4C6 bond takes place. In addition, the values of the local electrophilicity and local nucleophilcity indices in the framework of conceptual density functional theory accounts for the asychronicity of the process as well as for the observed regioselectivity. © 2012 Wiley Periodicals, Inc.
Nickel removal characteristics of an immobilized macro fungus: equilibrium, kinetic and mechanism analysis of the biosorption
Authors: Akar Tamer , Celik Sema , Gorgulu Ari Asli , Tunali Akar Sibel
Published: August 2012

BACKGROUND: An immobilized new biosorbent was prepared from macro fungi Lactarius salmonicolor for the effective removal of nickel ions from aqueous media. Operating conditions were optimized as functions of initial pH, agitation time, sorbent amount and dynamic flow rate. Immobilization and biosorption mechanism were examined and the developed biosorbent was tested for the removal of nickel ions from real wastewater.

RESULTS: Biosorption performance of the biomass continuously increased in the pH range 2.0–8.0. The coverage of the biosorbent surface by silica gel resulted in a significant increase in biosorption yield of nickel ions. The highest nickel loading capacity was obtained as 114.44 mg g−1 using a relatively small amount of immobilized biosorbent. Biosorption equilibrium time was recorded as 5 min. Experimental data were analyzed by different isotherm and kinetic models. Infrared spectroscopy, scanning electron microscopy and X‐ray energy dispersive analysis confirmed the process. The sorbent exhibited relatively good recovery potential in dynamic flow mode studies. Biosorption capacity of immobilized biosorbent was noted as 14.90 mg g−1 in real wastewater.

CONCLUSION: Silica gel immobilized biomass of L. salmonicolor is to be a low cost and potential biosorbent with high biosorption capacity for the removal of contaminating nickel from aqueous media. © 2012 Society of Chemical Industry
Benign enzymatic synthesis of multiwalled carbon nanotube composites uniformly coated with polypyrrole for supercapacitors
Authors: Ryu Keungarp , Xue Huahua , Park Junghee
Published: August 2012

BACKGROUND: Recently, various composites of carbon nanomaterials and conducting polymers have been actively investigated as potential electrode materials for supercapacitors which can store and deliver large amounts of electrical energy promptly. Harsh chemical or complex electrodeposition methods have been studied to prepare such composites. In this report, the mild and simple enzymatic catalysis of horseradish peroxidase (EC 1.11.1.7) in aqueous solutions (pH 4.0) was utilized for the first time to prepare composites of multiwalled carbon nanotubes and polypyrrole.

RESULTS: Electron micrographs show that in situ enzymatic reaction by horseradish peroxidase enables the uniform coating of multiwalled carbon nanotubes with polypyrrole without containing the polymer aggregates. The specific capacitance of the composites (46.2 F g−1) measured with a two‐electrode cell containing an electrolyte of 1 mol L−1 NaNO3 increased more than four‐fold compared with that obtained with bare multiwalled carbon nanotubes (10.8 F g−1).

CONCLUSIONS: Horseradish peroxidase‐catalyzed in situ synthesis of the composites of multiwalled carbon nanotubes and polypyrrole requires neither the derivatization of multiwalled carbon nanotubes and/or pyrrole monomers nor the post‐doping of the synthesized composites to enhance the capacitance of the composites. © 2012 Society of Chemical Industry
Remote sonographic interpretation: Comparison of standardized video clips to still images
Authors: Parsai Arman , Zerizer Imene , Hohmann Joachim , Bongartz Georg , Beglinger Christoph , Sperandeo Giuseppe
Published: August 2012

Objective.

The aim of our study was to evaluate the role of standardized video clips compared with still images in the diagnostic accuracy of remote sonographic interpretation.

Methods.

We compared the remote interpretation of sonographic examinations acquired with a standardized video clip approach to examinations performed with still images alone in 60 patients with various hepatic and extrahepatic pathologies.

Results.

The use of video clips improved the diagnostic accuracy of sonographic studies interpreted remotely compared with the use of still images (p < 0.0001). The sensitivity, specificity, and positive and negative predictive values increased from 47.3% to 68.3%, 81.8% to 87.8%, 71.5% to 81%, and 63.8% to 74.5%, respectively.

Conclusions.

Standardized video clips are easy to obtain, less operator‐dependent than still images, and can be transferred to remote sites without loss of important data. We recommend this method in remote interpretation (teleradiology and distant consultation) of sonographic examinations. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 40:495–501, 2012
Immunolocalization, gene expression, and enzymatic activity of cyclooxygenases, prostaglandin e2‐9‐ketoreductase, and nitric oxide synthases in mediterranean buffalo (bubalus bubalis) corpora lutea during diestrus
Authors: Parillo F. , Catone G. , Maranesi M. , Gobbetti A. , Gasparrini B. , Russo M. , Boiti C. , Zerani M.
Published: August 2012

Immunopresence, gene expression, and enzymatic activity of cyclooxygenase 1 (COX1), COX2, PGE2‐9‐ketoreductase (PGE2‐9‐K), endothelial (eNOS), and inducible nitric oxide synthases (iNOS), and hormone in vitro production were examined in early, mid, late, and regressive buffalo corpora lutea (CL). COX1 immunosignals were detected in the cytoplasm of small luteal cells, COX2 in large luteal cells, and PGE2‐9‐K in all luteal cells. COX2 and PGE2‐9‐K immunosignals were greater in late CL. Immunopresence of both NOS types were evidenced in the nuclei and cytoplasm of all luteal cells, as well as in the nuclei of endothelial cells, during all stages studied. The eNOS and iNOS immunosignals increased during the early stage. COX1 transcripts were lower in late and regressive CL, COX2 in late, PGE2‐9‐K higher in regressive, and iNOS higher in early and lower in regressive CL. COX1 enzymatic activity was lower in regressive CL, COX2 increased in mid and late stages, and PGE2‐9‐K was higher in late CL. Endothelial NOS activity was higher during mid and late stages and lower in regressive, whereas iNOS was greater in late and lower in early. Progesterone in vitro release was higher in mid and lower in late phase, while PGF2α synthesis was higher in late CL and lower in regressive, and PGE2 was higher during regressive stage. These results support the idea that COX, NOS, and PGE2‐9‐K regulate buffalo CL life span. In particular, regressive CL seems involved in the development of the contralateral early CL, through the production of the luteotrophic PGE2. Microsc. Res. Tech., 2012. © 2012 Wiley Periodicals, Inc.
Does sepsis treatment differ between primary and overflow intensive care units?
Authors: Vishnupriya Kittane , Falade Olufunmilayo , Workneh Addisu , Chandolu Satish , Landis Regina , Elizabeth Kaweesa , Iyengar Reethi , Wright Scott , Sevransky Jonathan
Published: August 2012

BACKGROUND:

Sepsis is a major cause of death in hospitalized patients. Early goal‐directed therapy is the standard of care. When primary intensive care units (ICUs) are full, sepsis patients are cared for in overflow ICUs.

OBJECTIVE:

To determine if process‐of‐care measures in the care of sepsis patients differed between primary and overflow ICUs at our institution.

DESIGN:

We conducted a retrospective study of all adult patients admitted with sepsis between July 2009 and February 2010 to either the primary ICU or the overflow ICU.

MEASUREMENTS:

Baseline patient characteristics and multiple process‐of‐care measures, including diagnostic and therapeutic interventions.

RESULTS:

There were 141 patients admitted with sepsis to our hospital; 100 were cared for in the primary ICU and 41 in the overflow ICU. Baseline acute physiology and chronic health evaluation (APACHE II) scores were similar. Patients received similar processes‐of‐care in the primary ICU and overflow ICU with the exception of deep vein thrombosis (DVT) and gastrointestinal (GI) prophylaxis within 24 hours of admission, which were better adhered to in the primary ICU (74% vs 49%, P = 0.004, and 68% vs 44%, P = 0.012, respectively). There were no significant differences in hospital and ICU length of stay between the 2 units (9.68 days vs 9.73 days, P = 0.98, and 4.78 days vs 4.92 days, P = 0.97, respectively).

CONCLUSIONS:

Patients with sepsis admitted to the primary ICU and overflow ICU at our institution were managed similarly. Overflowing sepsis patients to non‐primary intensive care units may not affect guideline‐concordant care delivery or length of stay. Journal of Hospital Medicine 2012; © 2012 Society of Hospital Medicine
Effects of increased overnight supervision on resident education, decision‐making, and autonomy
Authors: Haber Lawrence A. , Lau Catherine Y. , Sharpe Bradley A. , Arora Vineet M. , Farnan Jeanne M. , Ranji Sumant R.
Published: August 2012

BACKGROUND:

New supervisory regulations highlight the challenge of balancing housestaff supervision and autonomy. To better understand the impact of increased supervision on residency training, we investigated housestaff perceptions of education, autonomy, and clinical decision‐making before and after implementation of an in‐hospital, overnight attending physician (nocturnist).

METHODS:

We established a nocturnist program in July 2010 at our academic, tertiary care medical center. We administered pre‐surveys and post‐surveys of internal medicine residents on night float rotation during the 2010–2011 academic year. We surveyed residents before and after experiencing the nocturnist program.

RESULTS:

Housestaff reported an increase in the clinical value of the night float rotation (3.95 vs 4.27, P = 0.01) and the adequacy of overnight supervision (3.65 vs 4.30, P < 0.0001) without a change in decision‐making autonomy (4.35 vs 4.45, P = 0.44). Trainees agreed that nocturnist supervision positively impacted patient outcomes (3.79 vs 4.30, P = 0.002). Housestaff contacted attendings more frequently for transfers from outside facilities (2.00 vs 3.20, P = 0.006), during adverse events (2.51 vs 3.25, P = 0.04), prior to ordering invasive diagnostics (1.75 vs 2.76, P = 0.004), and prior to vasopressor use (1.52 vs 2.40, P = 0.004). Residents' fear of revealing knowledge gaps and desire to make decisions independently did not change.

CONCLUSIONS:

Increased overnight supervision enhanced the clinical value of the night float rotation, increased rates of attending contact during critical clinical decision‐making, and improved perception of patient care. These changes occurred without a decrease in housestaff's perceived decision‐making autonomy. Journal of Hospital Medicine 2012; © 2012 Society of Hospital Medicine
Correlations among risk‐standardized mortality rates and among risk‐standardized readmission rates within hospitals
Authors: Horwitz Leora I. , Wang Yongfei , Desai Mayur M. , Curry Leslie A. , Bradley Elizabeth H. , Drye Elizabeth E. , Krumholz Harlan M.
Published: August 2012

BACKGROUND:

Hospital‐level, 30‐day risk‐standardized mortality and readmission rates are publicly reported for Medicare patients admitted with acute myocardial infarction (AMI), heart failure (HF), and pneumonia, but the correlations among mortality rates and among readmission rates within US hospitals for these conditions are unknown. Correlation among measures within the same hospital would suggest that there are common hospital‐wide quality factors.

METHODS:

We designed a cross‐sectional study of US hospital 30‐day risk‐standardized mortality and readmission rates for Medicare fee‐for‐service beneficiaries from July 2007 to June 2009. We assessed the correlation between pairs of risk‐standardized mortality rates and pairs of risk‐standardized readmission rates for AMI, HF, and pneumonia.

RESULTS:

The mortality cohort included 4559 hospitals, and the readmission cohort included 4468 hospitals. Every mortality measure was significantly correlated with every other mortality measure (range of correlation coefficients, 0.27–0.41, P < 0.0001 for all correlations). Every readmission measure was significantly correlated with every other readmission measure (range of correlation coefficients, 0.32–0.47, P < 0.0001 for all correlations). For each condition pair and outcome, one‐third or more of hospitals were in the same quartile of performance. Correlations were highest within large, nonprofit, urban, and/or Council of Teaching Hospitals members. For any given condition pair, the correlation between readmission rates was significantly higher than the correlation between mortality rates (P < 0.01 for all pairs).

CONCLUSION:

Risk‐standardized readmission rates are moderately correlated with each other within hospitals, as are risk‐standardized mortality rates. This suggests that there may be common hospital‐wide factors affecting hospital outcomes. Journal of Hospital Medicine 2012. © 2012 Society of Hospital Medicine
Preparation of two D2 partial agonists in C‐14 and stable isotope labeled forms
Authors: Elmore Charles S. , Powell Mark E. , Xiong Hui , Wu Ye , Wang Lijuan , Saunders David , Urbanek Rebecca A.
Published: August 2012

In support of a program to develop a treatment for diseases resulting from an imbalance in dopamine levels, two drug candidates, 1 and 2, were prepared in stable isotope and C‐14 labeled forms. Both compounds contained an aminothiazole ring, and the C‐14 label was introduced into the ring using KS14CN. However, the use of KS14CN to form [14C]‐2 gave poor results; therefore, benzoyl [14C]isothiocyanate was used instead, which led to a much improved yield. The stable isotope labeled forms were prepared with the label in the side chain from [2H5]ethyl iodide for [2H5]‐1 and from 1‐[13C]methyl [15N2]pyrazole[13C]carboxaldehyde, which was prepared in turn from [carbonyl‐13C]DMF, [15N2]hydrazine sulfate, and [13C]methyliodide for [13C2, 15N2]‐2. Copyright © 2012 John Wiley & Sons, Ltd.
Subject‐specific models of susceptibility‐induced B0 field variations in breast MRI
Authors: Jordan Caroline D. , Daniel Bruce L. , Koch Kevin M. , Yu Huanzhou , Conolly Steve , Hargreaves Brian A.
Published: August 2012

Purpose:

To rapidly calculate and validate subject‐specific field maps based on the three‐dimensional shape of the bilateral breast volume.

Materials and Methods:

Ten healthy female volunteers were scanned at 3 Tesla using a multi‐echo sequence that provides water, fat, in‐phase, out‐of‐phase, and field map images. A shape‐specific binary mask was automatically generated to calculate a computed field map using a dipole field model. The measured and computed field maps were compared by visualizing the spatial distribution of the difference field map, the mean absolute error, and the 80% distribution widths of frequency histograms.

Results:

The 10 computed field maps had a mean absolute error of 38 Hz (0.29 ppm) compared with the measured field maps. The average 80% distribution widths for the histograms of all of the computed, measured, and difference field maps are 205 Hz, 233 Hz, and 120 Hz, respectively.

Conclusion:

The computed field maps had substantial overall agreement with the measured field maps, indicating that breast MRI field maps can be computed based on the air–tissue interfaces. These estimates may provide a predictive model for field variations and thus have the potential to improve applications in breast MRI. J. Magn. Reson. Imaging 2013;37:227–232. © 2012 Wiley Periodicals, Inc.
Accelerating three‐dimensional molecular cardiovascular MR imaging using compressed sensing
Authors: Prieto Claudia , Andia Marcelo E. , von Bary Christian , Onthank David C. , Schaeffter Tobias , Botnar Rene M.
Published: August 2012

Purpose:

To accelerate the acquisition of three‐dimensional (3D) high‐resolution cardiovascular molecular MRI by using Compressed Sensing (CS) reconstruction.

Materials and Methods:

Molecular MRI is an emerging technique for the early assessment of cardiovascular disease. This technique provides excellent soft tissue differentiation at a molecular and cellular level using target‐specific contrast agents (CAs). However, long scan times are required for 3D molecular MRI. Parallel imaging can be used to speed‐up these acquisitions, but hardware considerations limit the maximum acceleration factor. This limitation is important in small‐animal studies, where single‐coils are commonly used. Here we exploit the sparse nature of molecular MR images, which are characterized by localized and high‐contrast biological target‐enhancement, to accelerate data acquisition. CS was applied to detect: (a) venous thromboembolism and (b) coronary injury and aortic vessel wall in single‐ and multiple‐coils acquisitions, respectively.

Results:

Retrospective undersampling showed good overall image quality with accelerations up to four for thrombus and aortic images, and up to three for coronary artery images. For higher acceleration factors, features with high CA uptake were still well recovered while low affinity targets were less preserved with increased CS undersampling artifacts. Prospective undersampling was performed in an aortic image with acceleration of two, showing good contrast and well‐defined tissue boundaries in the contrast‐enhanced regions.

Conclusion:

We demonstrate the successful application of CS to preclinical molecular MR with target specific gadolinium‐based CAs using retrospective (accelerations up to four) and prospective (acceleration of two) undersampling. J. Magn. Reson. Imaging 2012; 36:1362–1371. © 2012 Wiley Periodicals, Inc.
Cervical muscle area measurements in whiplash patients: Acute, 3, and 6 months of follow‐up
Authors: Ulbrich Erika J. , Aeberhard Ramon , Wetli Sylvia , Busato Andre , Boesch Chris , Zimmermann Heinz , Hodler Juerg , Anderson Suzanne E. , Sturzenegger Matthias
Published: August 2012

Purpose:

To investigate the role of the cervical spine muscles in whiplash injury. We hypothesized that (i) cervical muscle hypotrophy would be evident after a 6‐month follow‐up and, (ii) cervical muscle hypotrophy would correlate with symptom persistence probably related to pain or inactivity.

Materials and Methods:

Ninety symptomatic patients (48 females) were recruited from our emergency department and examined within 48 h, and at 3, and 6 months after a motor vehicle accident. MRI cross‐sectional muscle area (CSA) measurements were performed bilaterally of the cervical extensor and sternocleidomastoid muscles using transverse STIR (Short Tau inversion Recovery) sequences at the C2 (deep and total dorsal cervical extensor muscles), C4 (sternocleidomastoid muscles) and C5 (deep and total dorsal cervical extensor muscles) levels. Two blinded raters independently performed the measurements at each time point. First, CSA changes over time were analyzed and, second, CSAs were correlated with clinical outcomes (EuroQuol, Whiplash Disability Score, neck pain intensity [VAS], cervical spine mobility).

Results:

There was a high agreement of CSA measurements between the two raters. Women consistently had smaller CSAs than men. There were no significant changes of CSAs over time at any of the three levels. There were no consistent significant correlations of CSA values with the clinical scores at all time points except with the body mass index.

Conclusion:

Our results do not support a major role of cervical muscle volume in the genesis of symptoms after whiplash injury. J. Magn. Reson. Imaging 2012; 36:1413–1420. © 2012 Wiley Periodicals, Inc.
Reduction of sodium and increment of calcium and ω‐3 polyunsaturated fatty acids in dry fermented sausages: effects on the mineral content, lipid profile and sensory quality
Authors: García‐Íñiguez de Ciriano Mikel , Berasategi Izaskun , Navarro‐Blasco Íñigo , Astiasarán Iciar , Ansorena Diana
Published: August 2012

BACKGROUND: A combined technological approach was applied in the development of healthier dry fermented sausages: a partial substitution of the pork back fat by pre‐emulsified linseed oil and a partial replacement of sodium chloride with calcium ascorbate at two different levels, leading to low amounts of salt (14gSalt and 10gSalt, with 14 g and 10 g NaCl per kg of mixture, respectively).

RESULTS: The developed products (14gSalt and 10gSalt) showed adequate results for aw (0.85 and 0.87) and pH (4.98 and 5.21), and low lipid oxidation values (1.4 × 10−4 and 1.5 × 10−5 g malondialdehyde (MDA) kg−1). The lipid modification led to a significantly higher supply of ω‐3 (23.3 g kg−1) compared to the control (3.2 g kg−1). Simultaneously, reductions of 38% and 50% in sodium content and a calcium supply of 4 and 5.2 g kg−1 were achieved in the 14gSalt and 10gSalt formulations, respectively, compared to the control products (26 g salt and 0.87 g kg−1 Ca). Instrumental analysis of colour and texture and sensory studies demonstrated that the organoleptic quality of the new formulations was similar to that of traditional products.

CONCLUSIONS: The developed dry fermented sausages showed healthier properties than traditional ones owing to their reduced sodium and higher calcium content and a significant supply of ω‐3 fatty acids. © 2012 Society of Chemical Industry
A new strategy for improved glutathione production from Saccharomyces cerevisiae: use of cysteine‐ and glycine‐rich chicken feather protein hydrolysate as a new cheap substrate
Authors: Taskin Mesut
Published: August 2012

BACKGROUND: Glutathione (GSH) is composed of the amino acids glutamic acid, cysteine and glycine. This study investigated the usability of chicken feather protein hydrolysate (chicken feather peptone, CFP) as a substrate for GSH production from Saccharomyces cerevisiae.

RESULTS: CFP was found to be rich in ash (36.7 g per 100 g), protein (61.1 g per 100 g) and minerals (S, P, K, Ca, Fe, Na and Mg). It also had high contents of cysteine and glycine. CFP augmented biomass and GSH production by 53 and 115% respectively compared with the control medium. The highest biomass (17.4 g l−1) and GSH (271 mg L−1) concentrations were attained in CFP medium. The second highest biomass (16.8 g l−1) and GSH (255 mg L−1) concentrations were obtained in fish peptone medium. It was assumed that the high mineral, cysteine and glycine contents of CFP were related to cell growth and GSH synthesis in S. cerevisiae.

CONCLUSION: This is the first report on the effect of cysteine‐ and glycine‐rich protein hydrolysates on GSH production from S. cerevisiae. In this regard, CFP was tested for the first time as a GSH production substrate. As an additional contribution, a new hydrolysis process was developed for the preparation of protein hydrolysates. © 2012 Society of Chemical Industry
Multi‐method comparison of carrot quality from a conventional and three organic cropping systems with increasing levels of nutrient recycling
Authors: Paoletti Flavio , Raffo Antonio , Kristensen Hanne L , Thorup‐Kristensen Kristian , Seljåsen Randi , Torp Torfinn , Busscher Nicolaas , Ploeger Angelica , Kahl Johannes
Published: August 2012

BACKGROUND: There is a need to advance the study of the effects of organic and conventional systems on product quality. In particular, little is known about the importance of different farming practices concerning nutrient cycling and the use of external inputs within organic farming for the quality characteristics of the products. In this study the quality characteristics of carrot grown under different farming practices (conventional and three organic cropping systems) over a two‐year period were analysed with the aim of discriminating between organic and conventional and investigating the effect of different organic farming practices concerning nutrient recycling and use of external nutrient input.

RESULTS: All quality characteristics measured did not give a clear differentiation between the carrots from the different growing systems, even when multivariate statistical evaluation (principal component analysis) was applied, because of the significance of the differences between the field replicates within each management system and of the seasonality. Only some tendencies were emphasised over the two years that could be related to the fertilisation practices and the external inputs used.

CONCLUSION: The results indicated that it was not possible to discriminate over the years between carrots from conventional and different organic cropping systems even though controlled conditions and a multi‐method approach of analysis were adopted. Copyright © 2012 Society of Chemical Industry
Method to improve color reproduction on a 120‐Hz two‐field color‐sequential LCD
Authors: Hammer Martin , Baar Teun , Zhang Yuning , Hinnen Karel J. G. , Langendijk Erno H. A.
Published: August 2012

Conventional displays use at least three primaries for full‐color image reproduction. In this contribution, the reproduction of color images using an LCD system with two local dynamic primaries, based on a segmented backlight, will be discussed. The two primaries are chosen to minimize color error by means of total least squares. Simulation results indicate quite good color reproduction for a large set of video data even with a limited number of backlight segments. A statistical analysis of this video content shows that excellent color reproduction (∆u′v′ < 0.020 for more than 99.0% of the pixels per frame) can be achieved for 74.2% of the frames using 9216 backlight segments.
Comparison of different imidazolium supported ionic liquid polymeric phases with strong anion‐exchange character for the extraction of acidic pharmaceuticals from complex environmental samples
Authors: Bratkowska Dominika , Fontanals Núria , Ronka Sylwia , Trochimczuk Andrzej W. , Borrull Francesc , Marcé Rosa M.
Published: August 2012

Two imidazolium supported ionic liquid phases (SILPs) containing different anions, trifluoromethanesulphonate [CF3SO3−], and tetrafluoroborate [BF4−], were synthesized and evaluated as solid‐phase extraction sorbents for extracting acidic pharmaceuticals from aqueous samples under strong anion‐exchange conditions, which include an effective cleanup of the sample. The best SILP material [MI+][CF3SO3−] was selected and successfully applied to the determination of acidic pharmaceuticals in different types of water samples (river water and effluent wastewater). The results were then compared to the previously synthesized SILP material based on [MI+][CF3COO−] and the commercially available Oasis MAX sorbent.