bluuebunny/crossref_metadata_2025 huggingface dataset:
Organization of the posterior parietal cortex in galagos: I. Functional zones identified by microstimulation
Authors: Stepniewska Iwona , Fang Pei‐Chun Y. , Kaas Jon H.
Published: August 2009

We used half‐second trains of intracortical microstimulation to study the functional organization of the posterior parietal cortex (PPC) in prosimian galagos. These trains of current pulses evoked meaningful behaviors from the anterior, but not posterior, half of PPC. Stimulation of dorsal PPC caused contralateral forelimb movements, including defensive, hand‐to‐mouth, and reaching movements. Defensive and hand‐to‐mouth movement territories overlapped, although hand‐to‐mouth movements were usually evoked from more rostrolateral sites than defensive movements. Reaching movement sites were typically more caudal than defensive or hand‐to‐mouth movement sites. Stimulation of the most medial PPC sites evoked complex movements of forelimbs and hindlimbs. Ventral PPC commonly represented defensive face movements. Similar defensive movements, with the addition of widely opening the mouth to expose the teeth, were elicited from a small area in front of the PPC defensive face zone. Sometimes defensive face movements occurred with forelimb movements. Thus, subregions of PPC relate to different ethologically relevant categories of behavior. Most movements were initiated within 33–100 msec after stimulus onset. Face, eye blink, and ear movements were generally less delayed than forelimb movements. The present results in galagos, together with those obtained from macaque monkeys by Graziano and coworkers (Graziano et al. [2002a] Neuron 34:841–851; Cooke et al., [2003] Proc. Natl. Acad. Sci. U.S.A. 100:6163–6168), suggest that the functional involvement of the PPC in specific types of sensorimotor behavior evolved early in the course of primate evolution and that networks for complex movements involving motor and posterior parietal areas are characteristic of all primate brains. J. Comp. Neurol. 517:765–782, 2009. © 2009 Wiley‐Liss, Inc.
Two novel neuropeptides in innervation of the salivary glands of the black‐legged tick,Ixodes scapularis: Myoinhibitory peptide and SIFamide
Authors: Šimo Ladislav , Itňan Dušan Žitňan , Park Yoonseong
Published: August 2009

The peptidergic signaling system is an ancient cell–cell communication mechanism that is involved in numerous behavioral and physiological events in multicellular organisms. We identified two novel neuropeptides in the neuronal projections innervating the salivary glands of the black‐legged tick,Ixodes scapularis(Say, 1821). Myoinhibitory peptide (MIP) and SIFamide immunoreactivities were colocalized in the protocerebral cells and their projections terminating on specific cells of salivary gland acini (types II and III). Immunoreactive substances were identified by matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF) analysis: a 1,321.6‐Da peptide with the sequence typical for MIP (ASDWNRLSGMWamide) and a 1,395.7‐Da SIFamide (AYRKPPFNGSIFamide), which are highly conserved among arthropods. Genes encoding these peptides were identified in the availableIxodesgenome and expressed sequence tag (EST) database. In addition, the cDNA encoding the MIP prepropeptide was isolated by rapid amplification of cDNA ends (RACE). In this report, we describe the anatomical structure of specific central neurons innervating salivary gland acini and identify different neuropeptides and their precursors expressed by these neurons. Our data provide evidence for neural control of salivary gland by MIP and SIFamide from the synganglion, thus leading a basis for functional studies of these two distinct classes of neuropeptides. J. Comp. Neurol. 517:551–563, 2009. © 2009 Wiley‐Liss, Inc.
Synaptic inputs onto small bistratified (blue‐ON/yellow‐OFF) ganglion cells in marmoset retina
Authors: Percival Kumiko A. , Jusuf Patricia R. , Martin Paul R. , Grünert Ulrike
Published: August 2009

The inner plexiform layer of the retina contains functional subdivisions, which segregate ON and OFF type light responses. Here, we studied quantitatively the ON and OFF synaptic input to small bistratified (blue‐ON/yellow‐OFF) ganglion cells in marmosets (Callithrix jacchus). Small bistratified cells display an extensive inner dendritic tier that receives blue‐ON input from short‐wavelength‐sensitive (S) cones via blue cone bipolar cells. The outer dendritic tier is sparse and is thought to receive yellow‐OFF input from medium (M)‐ and long (L)‐wavelength‐sensitive cones via OFF diffuse bipolar cells. In total, 14 small bistratified cells from different eccentricities were analyzed. The cells were retrogradely labeled from the koniocellular layers of the lateral geniculate nucleus and subsequently photofilled. Retinal preparations were processed with antibodies against the C‐terminal binding protein 2, the AMPA receptor subunit GluR4, and/or gephyrin to identify bipolar and/or amacrine input. The results show that the synaptic input is evenly distributed across the dendritic tree, with a density similar to that reported previously for other ganglion cell types. The population of cells showed a consistent pattern, where bipolar input to the inner tier is about fourfold greater than bipolar input to the outer tier. This structural asymmetry of bipolar input may help to balance the weight of cone signals from the sparse S cone array against inputs from the much denser M/L cone array. J. Comp. Neurol. 517:655–669, 2009. © 2009 Wiley‐Liss, Inc.
SynCAM1 expression correlates with restoration of central synapses on spinal motoneurons after two different models of peripheral nerve injury
Authors: Zelano Johan , Berg Alexander , Thams Sebastian , Hailer Nils P. , Cullheim Staffan
Published: August 2009

SynCAM1 and neuroligins (NLGs) are adhesion molecules that govern synapse formation in vitro. In vivo, the molecules are expressed during synaptogenesis, and altered NLG function is linked to synapse dysfunction in autism. Less is known about SynCAM1 and NLGs in adult synapse remodeling. CNS synapse elimination occurs after peripheral nerve injury, which causes a transient decrease in synapse number on spinal motoneurons. Here we have studied the expression of SynCAM1 and NLGs in relation to changes in synaptic covering on spinal motoneurons. We performed sciatic nerve transection (SNT) or crush (SNC), axotomy models that result in poor or good conditions for axon regeneration, respectively. The two lesions resulted in similar synapse elimination and in poor (SNT) and good (SNC) return of synapses after 70 days. Functional recovery was good after SNC but absent after SNT. SynCAM1 mRNA decreased after 14 days in both models and was restored 70 days after SNC, but not after SNT. NLG2 and ‐3 mRNAs decreased to a smaller degree after SNC than after SNT. Synaptophysin immunoreactivity correlated with SynCAM1 mRNA 70 days after SNT and NLG2 mRNA 70 days after SNC. Surprisingly, an inverse correlation was seen between NLG3 mRNA and Vglut2, a marker for excitatory synapses, 70 days after SNT. We conclude that 1) SynCAM1 mRNA levels seem to reflect the loss and restoration of synapses on motoneurons, 2) down‐regulation of NLGs is not a prerequisite for synapse elimination, and 3) expression of SynCAM1 and NLGs is regulated by different mechanisms during regeneration. J. Comp. Neurol. 517:670–682, 2009. © 2009 Wiley‐Liss, Inc.
In vivo depletion of DC impairs the anti‐tumor effect of agonistic anti‐CD137 mAb
Authors: Murillo Oihana , Dubrot Juan , Palazón Asís , Arina Ainhoa , Azpilikueta Arantza , Alfaro Carlos , Solano Sarai , Ochoa María C. , Berasain Carmen , Gabari Izaskun , Pérez‐Gracia José. L. , Berraondo Pedro , Hervás‐Stubbs Sandra , Melero Ignacio
Published: August 2009

Anti‐CD137 mAb are capable of inducing tumor rejection in several syngeneic murine tumor models and are undergoing clinical trials for cancer. The anti‐tumor effect involves co‐stimulation of tumor‐specific CD8+ T cells. Whether antigen cross‐presenting DC are required for the efficacy of anti‐CD137 mAb treatment has never been examined. Here we show that the administration of anti‐CD137 mAb eradicates EG7‐OVA tumors by a strictly CD8β+ T‐cell‐dependent mechanism that correlates with increased CTL activity. Ex vivo analyses to determine the identity of the draining lymph node cell type responsible for tumor antigen cross‐presentation revealed that CD11c+ cells, most likely DC, are the main players in this tumor model. A minute number of tumor cells, revealed by the presence of OVA cDNA, reach tumor‐draining lymph nodes. Direct antigen presentation by tumor cells themselves also participates in anti‐OVA CTL induction. Using CD11c diphtheria toxin receptor‐green fluorescent protein→C57BL/6 BM chimeric mice, which allow for sustained ablation of DC with diphtheria toxin, we confirmed the involvement of DC in tumor antigen cross‐presentation in CTL induction against OVA257–264 epitope and in the antitumor efficacy induced by anti‐CD137 mAb.
The Synthesis, Structure, and FTIR Spectroelectrochemistry of W(CO)5 Complexes of 4‐Oxo‐4‐(2,5‐dimethylazaferrocen‐1′‐yl)butanoic and 5‐Oxo‐5‐(2,5‐dimethylazaferrocen‐1′‐yl)pentanoic Acids
Authors: Kowalski Konrad , Winter Rainer F. , Makal Anna , Pazio Aleksandra , Woźniak Krzysztof
Published: August 2009

With the aim of developing new IR‐detectable metal–carbonyl tracers for the amino function, we have synthesized W(CO)5 complexes of 4‐oxo‐4‐(2,5‐dimethylazaferrocen‐1′‐yl)butanoic acid (2) and 5‐oxo‐5‐(2,5‐dimethylazaferrocen‐1′‐yl)pentanoic acid (3) by AlCl3‐catalyzed Friedel–Crafts reaction of W(CO)5–2,5‐dimethylazaferrocene (1) with succinic or glutaric anhydride. Complexes 2 and 3 are thermally stable and display sharp, intense absorption bands of tungsten‐coordinated CO ligands at ca. 1923 cm–1. In the crystalline state, molecules of 2 and 3 are stabilized by a network of intra‐ and intermolecular hydrogen bonds, as shown by single‐crystal X‐ray structure analysis. Complex 2 was transformed into the corresponding N‐succinimidyl ester 4. Its utility toward labeling of amino acids was tested in its reaction with glycine methyl ester. Corresponding glycine amide 5 was obtained in 82 % yield and is an air/thermally stable bioconjugate exhibiting intense sharp absorption bands of the W–CO reporting group at ca. 1923 cm–1. Cyclic voltammetry of 1, 2, 3, and acetyl derivative 6 shows the presence of two redox events in each case. The first redox couple is ascribed as an azaferrocene‐centered oxidation–reduction, whereas the second, irreversible process at higher potential originates from a W(CO)5‐centered oxidation. FTIR spectroelectrochemistry allowed us to monitor the spectroscopic changes accompanying the 1/1·+, 2/2·+, and 6/6·+ redox transformations. Significant W–CO absorption band shifts were recorded in the course of these experiments.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
An Economical Access to 3,4‐Diaryl‐2(5H)‐furanones and 4‐Aryl‐6‐methyl‐2(2H)‐pyranones by Pd‐Catalyzed Suzuki‐Type Arylation of 3‐Aryl‐4‐tosyloxy‐2(5H)‐furanones and 6‐Methyl‐4‐tosyloxy‐2(2H)‐pyranones, Respectively
Authors: Bellina Fabio , Marchetti Chiara , Rossi Renzo
Published: August 2009

Both symmetrical and unsymmetrical 3,4‐diaryl‐substituted 2(5H)‐furanones have been efficiently synthesized using an inexpensive procedure involving the Pd(OAc)2/PCy3‐catalyzed Suzuki‐type arylation of readily available 3‐aryl‐4‐tosyloxy‐2(5H)‐furanones as the key step. The mild conditions of this arylation protocol have also been used for the high yielding synthesis of 4‐aryl‐6‐methyl‐2(2H)‐pyranones from 6‐methyl‐4‐tosyloxy‐2(2H)‐pyranone. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Small molecule antagonists of Tcf4/β‐catenin complex inhibit the growth of HCC cells in vitro and in vivo
Authors: Wei Wei , Chua Mei‐Sze , Grepper Susan , So Samuel
Published: August 2009

Hepatocellular carcinoma (HCC) is the 5th most common cancer worldwide. It is intrinsically resistant toward standard chemotherapy, making it imperative to develop novel selective chemotherapeutic agents. The Wnt/β‐catenin pathway plays critical roles in development and oncogenesis, and is dysregulated in HCC. Our study aims to evaluate the activity of 3 small molecule antagonists of the Tcf4/β‐catenin complex (PKF118‐310, PKF115‐584 and CGP049090) on HCC cell lines in vitro and in vivo. All 3 chemicals displayed dose‐dependent cytotoxicity in vitro against all 3 HCC cell lines (HepG2, Hep40 and Huh7), but were at least 10 times less cytotoxic to normal hepatocytes (from 3 donors) by using ATP assay. In HepG2 and Huh7 cells, treatment with the antagonists decreased Tcf4/β‐catenin binding capability and transcriptional activity, associated with downregulation of the endogenous Tcf4/ β‐catenin target genes c‐Myc, cyclin D1 and survivin. In HepG2 and Huh7 cells, treatment with the antagonists induced apoptosis and cell cycle arrest at the G1/S phase. All antagonists suppressed in vivo tumor growth in a HepG2 xenograft model, associated with apoptosis and reduced c‐Myc, cyclin D1 and survivin expressions. Our results suggest that these 3 antagonists of the Tcf4/β‐catenin complex are potential chemotherapeutic agents which may offer a pathway specific option for the clinical management of HCC.
Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients
Authors: Lu Janice , Fan Tina , Zhao Qiang , Zeng Wei , Zaslavsky Eva , Chen John J. , Frohman Michael A. , Golightly Marc G. , Madajewicz Stefan , Chen Wen‐Tien
Published: August 2009

Recent research advances show that tumor cell intravasation (entry into the circulation) and metastasis occur very early in breast cancer progression. Clinical studies also illustrate the potential importance of detection of circulating tumor cells (CTCs) in outcomes of patients with metastatic breast cancer. Whether these cells exhibit the invasiveness and express tumor stem or progenitor markers, hallmark of the metastatic phenotype, is less well characterized. To detect CTCs with the invasive phenotype and to explore their molecular features, we applied a functional cell separation method, called collagen adhesion matrix (CAM) assay, as enrichment and identification steps. The CAM‐coated device successfully recovered tumor cells spiked in 1 ml of blood with a 54% ± 9% (n = 18) recovery rate and 0.5–35% purity, and detected invasive tumor cells in 10/10 blood samples (100% yield) from patients with metastatic breast cancer with a range of 18–256 CTCs/ml and average of 126 ± 25 (mean ± SD) CTCs/ml. CTCs were detected in blood samples of 28/54 (52%) Stage I–III breast cancer patients with a mean count of 61 CTCs/ml. Furthermore, the relative frequency of these cells correlated to the staging, lymph node‐status and survival of patients with early stage breast cancer. CAM‐captured cells were capable of propagation in culture. Gene expression and multiplex flow cytometric analyses on CAM‐captured cells demonstrated the existence of distinct populations of CTCs including these of epithelial lineage and stem or progenitor cells. Thus, CAM‐initiated CTC detection provides advantages for examining invasiveness and tumor progenitor phenotypes.
A highly stable whole‐cell biocatalyst for the enantioselective synthesis of optically active alpha‐hydroxy acids
Authors: Guo Jinling , Mu Xiaoqing , Zheng Changge , Xu Yan
Published: August 2009

BACKGROUND: Biocatalysts have gained increasing attention because of their inherent advantages over chemical catalysts. However, the poor operational stability has always prevented their broad application. In this study, (R)‐mandelic acid was chosen as a model compound of alpha‐hydroxy acids. The objective was to obtain a new biocatalyst with desired operational stability for the preparation of (R)‐mandelic acid as well as other optically pure alpha‐hydroxy acids of pharmaceutical importance.

RESULTS: Using a two‐step screening strategy, Saccharomyces ellipsoideus GIM2.105 was selected as an effective biocatalyst with high enantioselectivity and remarkable operational stability. After 20 cycles of reuse, whole cells of S. ellipsoideus GIM2.105 maintained its activity, and no obvious decrease in conversion or enantiomeric excess (ee) was observed. Furthermore, effects of various reaction parameters, including pH, temperature, co‐substrate (type, concentration), substrate concentration and reaction time, on the bioreduction were studied. Under optimal conditions, (R)‐mandelic acid and four substituted aromatic (R)‐alpha‐hydroxy acids were prepared in high ee (95–>99%) and good conversion (>90%).

CONCLUSION: The high enantioselectivity, remarkable operational stability and mild reaction conditions showed S. ellipsoideus GIM2.105 to be an economical biocatalyst with great industrial application potential for the production of optically active alpha‐hydroxy acids. Copyright © 2009 Society of Chemical Industry
Tip‐induced heating in apertureless near‐field optics
Authors: Malkovskiy A. V. , Malkovsky V. I. , Kisliuk A. M. , Barrios C. A. , Foster M. D. , Sokolov A. P.
Published: August 2009

Tip‐enhanced Raman spectroscopy is considered a promising technique for imaging with nanoscale lateral resolution. However, its developments and use face many problems. In this paper we provide insight into the level of sample heating by the laser light in the presence of a metal‐coated atomic force microscope (AFM) tip. The heating is attributed to the presence of an optical field enhanced by the tip. Sample temperatures were estimated using measurements of the ratio of the Stokes and anti‐Stokes signals from a thin 50‐nm sample on an Al substrate. A correlation between the heating and optical properties of the tips is established. The results demonstrate significant tip‐induced heating (100 K and more) even at very low laser power. Copyright © 2009 John Wiley & Sons, Ltd.
Global benefit–risk analysis of adjunctive aripiprazole in the treatment of patients with major depressive disorder
Authors: Wisniewski, PhD Stephen R. , Chen, PhD Chi‐Chang , Kim, MD, MBA Edward , Kan, PhD Hong J. , Guo, PhD Zhenchao , Carlson, PhD Berit X. , Tran, Pharm D, BCPP Quynh‐Van , Pikalov, MD, PhD Andrei
Published: August 2009

Objective

This study quantified the overall merit of adjunctive aripiprazole in major depressive disorder (MDD).

Methods

Global benefit–risk (GBR) analysis quantified the benefit and risk differences between adjunctive aripiprazole and antidepressant (ADT) monotherapy. Three hundred and fifty six patients receiving ADT monotherapy and 366 patients receiving ADT and adjunctive aripiprazole (2–20 mg/day) were included. Efficacy measures included the Montgomery–Åsberg depression rating scale (MADRS) Total score response (≥50% reduction) and remission (response plus Total score ≤ 10). Treatment‐emergent adverse events were classified by severity. GBR ratio measures evaluated the relative benefit of adjunctive aripiprazole. Logistic regression models tested the effect of adjunctive aripiprazole on GBR and were used to identify predictors of net benefit and potential factors affecting the adjunctive aripiprazole treatment effect.

Results

For MADRS‐defined response and remission, the relative gain of adjunctive aripiprazole versus ADT monotherapy was 1.46 (p = 0.044) and 1.43 (p = 0.085), respectively. Gender, current escitalopram, duration of current episode, and baseline body mass index are potential factors affecting the adjunctive aripiprazole treatment effect.

Conclusions

Compared with ADT monotherapy, adjunctive aripiprazole was associated with an improved benefit–risk profile in MDD. Copyright © 2009 John Wiley & Sons, Ltd.
Temporal trends in anti‐diabetes drug use in tricare following safety warnings in 2007 about rosiglitazone
Authors: Stewart Kate A. , Natzke Brenda M. , Williams Thomas , Granger Elder , Casscells S. Ward , Croghan Thomas W.
Published: August 2009

Purpose

To describe utilization patterns for anti‐diabetes medications among a cohort of diabetes patients in the Military Health System (MHS) before and after warnings about rosiglitazone issued in May 2007.

Methods

We used segmented regression analysis to compare changes in the level and trend of rosiglitazone utilization and use of other anti‐diabetes therapies in the period prior to the drug warnings (between April 2006 and May 2007) and the period after the warnings were issued (between October 2007 and May 2008).

Results

The level and trend of rosiglitazone use changed after the highly publicized warnings. The number of prescriptions filled fell by almost 7000 after the warning (p < 0.001). The number of prescriptions filled for pioglitazone, sulfonylureas, and other diabetes drugs increased significantly after the warnings (p < 0.05 in all models). Overall, the level and trend of filled prescriptions per month for all anti‐diabetic drugs did not significantly change after the warnings.

Conclusions

Utilization patterns changed in response to warnings about rosiglitazone. While overall utilization of anti‐diabetic drugs did not change, further study is needed to determine the associated health outcomes. Copyright © 2009 John Wiley & Sons, Ltd.
Differential expression of cell surface proteins in human bone marrow mesenchymal stem cells cultured with or without basic fibroblast growth factor containing medium
Authors: Lee Sang Kwang , Kim Yongtae , Kim Sung‐Soo , Lee Jeong Hwa , Cho Kun , Lee Sang Sook , Lee Zee‐Won , Kwon Kyung‐Hoon , Kim Young Hye , Suh‐Kim Haeyoung , Yoo Jong Shin , Park Young Mok
Published: August 2009

Mesenchymal stem cells (MSCs) are multipotent cells, which have the capability to differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle, and marrow stroma. However, they lose the capability of multi‐lineage differentiation after several passages. It is known that basic fibroblast growth factor (bFGF) increases growth rate, differentiation potential, and morphological changes of MSCs in vitro. In this report, we have used 2‐DE coupled to MS to identify differentially expressed proteins at the cell membrane level in MSCs growing in bFGF containing medium. The cell surface proteins isolated by the biotin–avidin affinity column were separated by 2‐DE in triplicate experiments. A total of 15 differentially expressed proteins were identified by quadrupole‐time of flight tandem MS. Nine of the proteins were upregulated and six proteins were downregulated in the MSCs cultured with bFGF containing medium. The expression level of three actin‐related proteins, F‐actin‐capping protein subunit alpha‐1, actin‐related protein 2/3 complex subunit 2, and myosin regulatory light chain 2, was confirmed by Western blot analysis. The results indicate that the expression levels of F‐actin‐capping protein subunit alpha‐1, actin‐related protein 2/3 complex subunit 2, and myosin regulatory light chain 2 are important in bFGF‐induced morphological change of MSCs.
Reverse‐phase protein arrays for application‐orientated cancer research
Authors: Korf Ulrike , Löbke Christian , Sahin Özgür , Haller Florian , Sültmann Holger , Arlt Dorit , Poustka Annemarie
Published: August 2009

A detailed and quantitative analysis of disease‐relevant signaling will greatly contribute to our understanding of tumorigenesis and cancer progression, and thus open new strategies for drug discovery. However, throughput and sensitivity of currently established methods available for proteome profiling do not comply with the needs of clinical research such as high sample capacity and low sample consumption. Protein microarrays emerged as a promising alternative to analyze the abundance of proteins and their phosphorylation status on a high‐throughput level. Here we summarize recent methodological advancements in the field of reverse‐phase protein arrays and demonstrate their potential for clinical research as well as for in vitro applications.
Fabrication of Flexible Metal‐Nanoparticle Films Using Graphene Oxide Sheets as Substrates
Authors: Xu Chao , Wang Xin
Published: August 2009

Graphene‐based sheets that possess a unique nanostructure and a variety of fascinating properties are appealing as promising nanoscale building blocks of new composites. Herein, graphene oxide sheets are used as the nanoscale substrates for the formation of silver‐nanoparticle films. These silver‐nanoparticle films assembled on graphene oxide sheets are flexible and can form stable suspensions in aqueous solutions. They can also be easily processed, forming macroscopic films with high reflectivity. Raman signals of graphene oxide in such hybrid films are increased by the attached silver nanoparticles, displaying surface‐enhanced Raman scattering activity. The degree of enhancement can be adjusted by varying the quantity of silver nanoparticles on the graphene oxide sheets.
Clinical and Pathologic Differences Between BRCA1‐, BRCA2‐, and Non‐BRCA‐Associated Breast Cancers in a Multiracial Developing Country
Authors: Yip Cheng‐Har , Taib N. A. , Choo W. Y. , Rampal S. , Thong M. K. , Teo S. H.
Published: August 2009

Background

Mutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1‐ and BRCA2‐associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population.

Methods

We conducted a retrospective review of the medical records of 152 women with breast cancer who underwent genetic testing for BRCA mutations. The patients self‐reported ethnicity, age at onset, and clinical stage at diagnosis and tumor pathology were reviewed.

Results

A total of 31 patients carried germline deleterious mutations (16 BRCA1, 15 BRCA2). We found that tumors in BRCA1 carriers were more likely to be estrogen receptor (ER)‐negative and progesterone receptor (PR)‐negative. HER2 was more likely to be negative in both BRCA1 and BRCA2 subjects compared with non‐BRCA subjects. We found a strong association between triple‐negative status and BRCA1 carriers. In addition, tumors in BRCA1 carriers were more likely to be higher grade than those in BRCA2 and non‐BRCA carriers; but the difference was not statistically significant.

Conclusions

These results suggest that tumors associated with BRCA1 mutations are distinct from those of BRCA2‐associated and non‐BRCA‐associated breast cancers, and that the tumors associated with BRCA2 mutations are similar to the non‐BRCA‐associated breast cancers. Further studies are required to determine if the prognosis is different in each of these groups and the best management strategy for each group.
Gastric Emptying Function in Patients 5 Years After Pylorus‐Preserving Distal Gastrectomy With or Without Preserving Pyloric and Hepatic Branches of the Vagal Nerve for Early Gastric Cancer
Authors: Tomita Ryouichi
Published: August 2009

Background

To clarify the significance of preserving pyloric and hepatic branches of the vagal nerve (PHV) after pylorus preserving distal gastrectomy (PPG) for early gastric cancer, the author investigated the postgastrectomy syndrome and gastric emptying function at 5 years in PPG patients with or without preserving the PHV.

Methods

A total of 18 subjects (mucosal cancers) who underwent PPG with D1 lymph node dissection and preserving the PHV; they comprised group A—12 men and 6 women aged 38–68 years (mean 58.9 years). They were interviewed to inquire about gastrointestinal symptom (appetite, weight loss, gastric fullness, reflux esophagitis, early dumping syndrome) and then were compared with 24 PPG patients (submucosal cancers) with D2 lymph node dissection without preserving the PHV (group B—16 men and 8 women aged 33 to 69 years, mean 60.1 years). Esophagogastric endoscopy, abdominal ultrasonography, and gastric emptying function tests (GET) were undertaken, the latter by both radioisotope (solid diet) and acetaminophen (liquid diet) methods.

Results

There were no differences in the postoperative gastrointestinal symptoms, endoscopic reflux esophagitis, or endoscopic mucosal edema and redness (gastropathy) between groups A and B. However, more cholecystolithiasis (gallbladder stones) was found in group A than in group B, with the difference being significant (P < 0.0391). The GET for solid diet and liquid diet were the almost same among groups A and B.

Conclusions

There were no significant differences in the postoperative QOL and GET between PPG patients with preserving PHV and those without preserving PHV. Cholecystolithiasis was only found in patients without preserving PHV.
A Meta‐Analysis of Randomized, Controlled Trials Assessing the Prophylactic Use of Ceftriaxone. A Study of Wound, Chest, and Urinary Infections
Authors: Woodfield J. C. , Beshay N. , van Rij A. M.
Published: August 2009

Background

Ceftriaxone is an effective prophylactic antibiotic. However, there is no consensus about whether ceftriaxone should be used as a first‐line antibiotic for the prevention of incisional surgical site infection (SSI). Its role in preventing urinary tract infection (UTI) and pneumonia also is controversial.

Methods

A meta‐analysis of randomized, controlled trials assessing the prophylactic use of ceftriaxone between 1983 and 2005 was performed. Medline, Embase, and Cochrane registers were reviewed. Additional references, review papers, and proceedings from meetings were searched. The Jadad score was used to assess study quality. A meta‐analysis with sensitivity analyses was performed for SSI, UTI, and pneumonia.

Results

Of 231 reviewed papers, 90 were included. Ceftriaxone prophylaxis was superior to other antibiotics in each category. Sixty‐one studies assessed the prevention of SSI (odds ratio (OR), 0.68; 95% confidence interval (CI), 0.53–0.7, p < 0.001; Cochran’s Q statistic, p = 0.93). The difference was greatest for abdominal surgery. There was no difference for cardiac surgery. Thirty‐five studies assessed the prevention of UTI (OR 0.53; 95% CI 0.43–0.63, p = 0; Cochran’s Q statistic, p = 0.97). The difference was greatest in obstetric and gynecological and colorectal surgery. Thirty‐seven studies assessed the prevention of pneumonia (OR 0.66; 95% CI 0.54–0.81, p = 0; Cochran’s Q statistic, p = 0.65). The difference was greatest in upper abdominal surgery.

Conclusions

The meta‐analysis confirms that prophylactic ceftriaxone is more effective than most other prophylactic antibiotics. This reduces SSI, UTI, and pneumonia in procedures where there is an increased risk of these infections. In such procedures, the data support using ceftriaxone as a first‐line prophylactic antibiotic.
Thick Melanoma: Prognostic Value of Positive Sentinel Nodes
Authors: Vermeeren Lenka , van der Ent Fred W. C. , Sastrowijoto Prapto S. H. , Hulsewé Karel W. E.
Published: August 2009

Background

Sentinel lymph node biopsy (SNB) is a widely accepted procedure used to accurately stage patients with melanoma. Its value in patients with thick melanoma (Breslow thickness >4 mm) is reason for discussion because of the generally poor prognosis of these patients. The purpose of this study was to report on the incidence of SNB positivity in patients with thick melanoma and to analyze the prognostic value of SNB in these patients.

Methods

The prospective database of 248 patients with cutaneous melanoma, who underwent SNB in the Maaslandhospital Sittard between January 1994 and August 2007, was reviewed and completed. In 31 patients, SNB was performed for a thick melanoma. We analyzed survival (Kaplan–Meier) and survival differences (log‐rank) in this group.

Results

In 64.5% of the patients with a thick melanoma, the SNB was positive. In our patients, SNB result was the only predictor for overall survival in patients with a thick melanoma (P = 0.045).

Conclusions

To be accurately informed about a patient’s prognosis and to decide whether subsequent completion lymph node dissection is indicated, SNB should not be omitted in patients with a primary thick melanoma.
Cardiovascular Risk in Patients with Nonfunctional Adrenal Incidentaloma: Myth or Reality?
Authors: Erbil Yesim , Ozbey Nese , Barbaros Umut , Unalp Haluk Recai , Salmaslıoglu Artur , Özarmagan Selçuk
Published: August 2009

Background

It is not clear whether nonfunctional adrenal incidentaloma (NFA) increases the risk of atherosclerosis and metabolic syndrome or whether this type of adrenal tumor has been found more frequently in patients with cardiometabolic risk factors. We aimed to determine the effects of NFA on cardiometabolic risk factors and endothelial function and to compare the patients with a 1:1 cardiometabolic risk factor matched control group.

Methods

Thirty‐five patients with NFA were studied, and 35 body mass index‐, age‐, and sex‐matched subjects were regarded as group 2 controls. Thirty‐five cardiometabolic risk factors–matched subjects were then regarded as group 3 controls.

Results

Patients with NFA had significantly lower flow‐mediated dilation (FMD)—a parameter for endothelial function—measurements compared with groups 2 and 3 (7.1 ± 2.9% vs. 12.9 ± 3.8% and 13.5 ± 4.5%; P < 0.02). Frequency of metabolic syndrome was also significantly higher in NFA patients than in control groups 2 and 3 (31.4, 5.7, and 20.0%, respectively; P < 0.05). Age (Odds Ratio [OR] = 2.9), total cholesterol (OR = 2.3), and presence of adrenal incidentaloma (OR = 10) were significant independent predictors of lower FMD (P < 0.05 for all).

Conclusions

Patients with NFA have increased prevalence of metabolic syndrome and impaired endothelial function compared with 1:1 cardiometabolic risk factor–matched controls.
What ought probably means, and why you can’t detach it
Authors: Finlay Stephen
Published: August 2009

Some intuitive normative principles raise vexing ‘detaching problems’ by their failure to license modus ponens. I examine three such principles (a self-reliance principle and two different instrumental principles) and recent stategies employed to resolve their detaching problems. I show that solving these problems necessitates postulating an indefinitely large number of senses for ‘ought’. The semantics for ‘ought’ that is standard in linguistics offers a unifying strategy for solving these problems, but I argue that an alternative approach combining an end-relational theory of normativity with a comparative probabilistic semantics for ‘ought’ provides a more satisfactory solution.
The life and production of the peasants in Huizhou from the late Qing Dynasty to the Republic of China: The analysis based on 5 day-to-day accounts in Wuyuan County
Authors: Zhifan HUANG , Hong SHAO
Published: August 2009

The Pairizhang (day-to-day accounts) found in Huizhou were mostly written by the pupils in old-style private school. They seem similar to a dairy in some way with the activities of family members (mostly male) as the main contents. However, they differ from modern diaries in many ways. It was a common practice in Wuyuan County to keep day-to-day accounts in the late Qing Dynasty and the Republic of China. By analyzing the 5 accounts found there, many underlying facts can be revealed, such as the time allocation of the main labor force, the composition of the peasant’s family economy, the general situation of productive activity and the days and ranges of their outdoor activity, etc. All these findings can help us have a better understanding of the peasants’ life in Huizhou at that time.
Binary Mixtures of SH- and CH3-Terminated Self-Assembled Monolayers to Control the Average Spacing Between Aligned Gold Nanoparticles
Authors: Rezaee Asad , Pavelka Laura C , Mittler Silvia
Published: August 2009

This paper presents a method to control the average spacing between organometallic chemical vapor deposition (OMCVD) grown gold nanoparticles (Au NPs) in a line. Focused ion beam patterned CH3-terminated self-assembled monolayers are refilled systematically with different mixtures of SH- and CH3-terminated silanes. The average spacing between OMCVD Au NPs is demonstrated systematically to decrease by increasing the v/v% ratio of the thiols in the binary silane mixtures with SH- and CH3-terminated groups.
Event-based prospective memory performance in autism spectrum disorder
Authors: Altgassen Mareike , Schmitz-Hübsch Maren , Kliegel Matthias
Published: August 2009

The purpose of the present study was to investigate event-based prospective memory performance in individuals with autism spectrum disorder and to explore possible relations between laboratory-based prospective memory performance and everyday performance. Nineteen children and adolescents with autism spectrum disorder and 19 matched neurotypical controls participated. The laboratory-based prospective memory test was embedded in a visuo-spatial working memory test and required participants to remember to respond to a cue-event. Everyday planning performance was assessed with proxy ratings. Although parents of the autism group rated their children’s everyday performance as significantly poorer than controls’ parents, no group differences were found in event-based prospective memory. Nevertheless, individual differences in laboratory-based and everyday performances were related. Clinical implications of these findings are discussed.
A Quality Committee's Evaluation of Surgical Intervention for Clostridium difficile Infection
Authors: Vasaly Fran White , Reines H. David
Published: August 2009

Clostridium difficile (C diff) is an anaerobic bacterium that causes antibiotic‐associated colitis, which can progress to a life‐threatening illness for some patients. Clostridium difficile is highly transmissible in health care settings and has high morbidity and mortality rates. The increased prevalence of this bacterium and the consequences of infection necessitate an understanding of its transmission and use of stringent infection control practices.

A two‐year retrospective evaluation was performed to examine the effectiveness of a screening tool for patients requiring surgical intervention for C diff and to determine whether treatment was timely and effective. Early, aggressive surgical intervention appears to be the single most effective treatment for fulminant C diff colitis. AORN J 90 (August 2009) 192–200. © AORN, Inc, 2009.
Antheraea pernyi silk fibroin maintains the immunosupressive properties of human bone marrow mesenchymal stem cells
Authors: Luan Xi‐Ying , Huo Guan‐Hua , Li Ming‐Zhong , Lu Shen‐Zhou , Zhang Xue‐Guang
Published: August 2009

We reported previously that regenerated Antheraea pernyi silk fibroin (A. pernyi SF) could support the attachment and growth of human bone marrow mesenchymal stem cells (hBMSCs). In this work, the immunosupressive effects of hBMSCs cultured on the A. pernyi SF films on T‐cells were investigated in vitro. The production of IL‐6, CD80, CD86 and HLA‐DR by the hBMSCs was also observed. The study showed that hBMSCs cultured on the regenerated A. pernyi SF films still kept their immunosupression on T‐cell proliferation and IL‐2 secretion. Moreover, regenerated A. pernyi SF like regenerated Bombyx mori SF and collagen did not elicit T‐cell proliferation but it could support the expression of IL‐6 and surface antigen of hBMSCs. Regenerated A. pernyi SF can maintain the function of hBMSCs in immunomodulation and cytokines production, which has the potential utility of hBMSCs combined with A. pernyi SF in tissue replacement and repair.
Short-term docosapentaenoic acid (22 : 5n-3) supplementation increases tissue docosapentaenoic acid, DHA and EPA concentrations in rats
Authors: Kaur Gunveen , Begg Denovan P. , Barr Daniel , Garg Manohar , Cameron-Smith David , Sinclair Andrew J.
Published: August 2009

The metabolic fate of dietaryn-3 docosapentaenoic acid (DPA) in mammals is currently unknown. The aim of the present study was to determine the extent of conversion of dietary DPA to DHA and EPA in rats. Four groups of male weanling Sprague–Dawley rats (aged 5 weeks) were given 50 mg of DPA, EPA, DHA or oleic acid, daily for 7 d by gavage. At the end of the treatment period, the tissues were analysed for concentrations of long-chain PUFA. DPA supplementation led to significant increases in DPA concentration in all tissues, with largest increase being in adipose (5-fold) and smallest increase being in brain (1·1-fold). DPA supplementation significantly increased the concentration of DHA in liver and the concentration of EPA in liver, heart and skeletal muscle, presumably by the process of retroconversion. EPA supplementation significantly increased the concentration of EPA and DPA in liver, heart and skeletal muscle and the DHA concentration in liver. DHA supplementation elevated the DHA levels in all tissues and EPA levels in the liver. Adipose was the main tissue site for accumulation of DPA, EPA and DHA. These data suggest that dietary DPA can be converted to DHA in the liver, in a short-term study, and that in addition it is partly retroconverted to EPA in liver, adipose, heart and skeletal muscle. Future studies should examine the physiological effect of DPA in tissues such as liver and heart.
THE MONARCHICAL REPUBLIC OF MARY I
Authors: HUNT ALICE
Published: August 2009

In his celebrated 1987 essay, ‘The monarchical republic of Queen Elizabeth I’, Patrick Collinson wrote that ‘Elizabethan England was a republic which also happened to be a monarchy: or vice versa.’ Since then, the idea of an Elizabethan ‘monarchical republic’ has been tested, challenged, and developed, with precedents found in Henry VIII's and Edward VI's reigns. Mary I's reign has not, however, been considered for its contribution to the debates. Yet, in 1553, the unique circumstances of Mary's accession as England's first queen regnant, who was also still legally a bastard, exacerbated sixteenth-century anxieties about monarchical authority, and about the correct relationship between a monarch and parliament. Prior to Mary's coronation, her council put forward an unprecedented proposal: they wanted parliament to sit before Mary was anointed and crowned queen. This article explores this proposal, in conjunction with two texts, Richard Taverner'sAn oration gratulatory made upon the joyfull proclayming of the moste noble Princes Quene Mary Quene of Englandeand the playRespublica, to argue that, at the beginning of her reign, significant pressure was put on Mary to rule her country as a ‘monarchical republic’.
PRESBYTERIAN RELIGION, HISTORIOGRAPHY, AND ULSTER SCOTS IDENTITY, c. 1800 TO 1914
Authors: HOLMES ANDREW R.
Published: August 2009

The links between Presbyterians in Scotland and the north of Ireland are obvious but have been largely ignored by historians of the nineteenth century. This article addresses this gap by showing how Ulster Presbyterians considered their relationship with their Scottish co-religionists and how they used the interplay of religious and ethnic considerations this entailed to articulate an Ulster Scots identity. For Presbyterians in Ireland, their Scottish origins and identity represented a collection of ideas that could be deployed at certain times for specific reasons – theological orthodoxy, civil and religious liberty, and certain character traits such as hard work, courage, and soberness. Ideas about the Scottish identity of Presbyterianism were reawakened for a more general audience in the first half of the nineteenth century, during the campaign for religious reform and revival within the Irish church, and were expressed through a distinctive denominational historiography inaugurated by James Seaton Reid. The formulation of a coherent narrative of Presbyterian religion and the improvement of Ulster laid the religious foundations of a distinct Ulster Scots identity and its utilization by unionist opponents of Home Rule between 1885 and 1914.
A taxonomic revision ofCaloplaca herbidellaandC. furfuracea
Authors: ARUP Ulf , ÅKELIUS Elin
Published: August 2009

Caloplaca herbidella(Hue) H. Magn. andC. furfuraceaH. Magn. are two isidiate, epiphytic species in the large genusCaloplaca.Caloplaca herbidellain a strict sense is normally grey and fertile with thick, somewhat coralloid isidia, but orange, sterile forms with thin isidia also occur.Caloplaca furfuraceais superficially similar morphologically toC. herbidellas. str. but has thinner, more granular isidia and generally a darker grey colour. Doubts have been raised as to whetherC. furfuraceashould be acknowledged as a proper species or incorporated inC. herbidella. Using morphometric methods and molecular analysis of the nrITS DNA gene we show thatC. herbidellaandC. furfuraceaare two clearly separated species. Furthermore, the mainly sterile, orange form ofC. herbidellacan be regarded as a separate species that is here described asC. corallizaArup & Åkelius. All three species are described in detail, including photographs and notes on their ecology. Finally, new distribution maps for Europe show thatC. herbidellaandC. corallizaare widespread in Europe, but the latter is probably less common than the former.Caloplaca furfuraceais clearly very rare in Europe with only few collections from Switzerland and Sweden, but seems to be more common in North America.
The pattern and course of cognitive impairment in late-life depression
Authors: Köhler S. , Thomas A. J. , Barnett N. A. , O'Brien J. T.
Published: August 2009

Background

Cognitive deficits persist despite clinical recovery in subjects with late-life depression, but more needs to be known about their longer-term outcome and factors affecting their course. To investigate this, we followed the pattern of cognitive impairments over time and examined the effects of current mood, remission status, age of depression onset and antidepressant (AD) treatment on these deficits.

Method

Sixty-seven subjects aged ⩾60 years with DSM-IV major depressive disorder and 36 healthy comparison subjects underwent tests of global cognition, memory, executive functioning and processing speed at baseline, 6 and 18 months, with some subjects tested again after 4 years. z scores were compared between groups, with analyses of clinical factors that may have influenced cognitive performance in depressed subjects.

Results

Half of the patients exhibited a generalized cognitive impairment (GCI) that persisted after 18 months. Patients performed worse across all cognitive domains at all time points, without substantial variability due to current mood, remission status or AD treatment. Late age of onset was associated significantly with decline in memory and executive functioning. Impaired processing speed may be a partial mediator of some deficits, but was insufficient to explain differences between patients and controls. Four-year follow-up data suggest impairments persist, but do not further decline.

Conclusions

Cognitive deficits in late-life depression persist up to 4 years, affect multiple domains and are related to trait rather than state effects. Differences in severity and course between early and late onset depression suggest different pathogenic processes.