bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolving postoperative neuroinflammation and cognitive decline
Authors: Terrando Niccolò , Eriksson Lars I. , Kyu Ryu Jae , Yang Ting , Monaco Claudia , Feldmann Marc , Jonsson Fagerlund Malin , Charo Israel F. , Akassoglou Katerina , Maze Mervyn
Published: October 2011

Objective:

Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved.

Methods:

C57BL/6J, Ccr2RFP/+Cx3cr1GFP/+, IkkF/F mice and LysM‐Cre/IkkF/F mice underwent stabilized tibial fracture operation under analgesia and general anesthesia. Separate cohorts of mice were tested for systemic and hippocampal inflammation, integrity of the blood–brain barrier (BBB), and cognition. The putative resolving effects of the cholinergic pathway on these postoperative responses were also studied.

Results:

Peripheral surgery disrupts the BBB via release of tumor necrosis factor‐alpha (TNFα), which facilitates the migration of macrophages into the hippocampus. Macrophage‐specific deletion of Ikappa B kinase (IKK)β, a central coordinator of TNFα signaling through activation of nuclear factor (NF) κB, prevents BBB disruption and macrophage infiltration in the hippocampus following surgery. Activation of the α7 subtype of nicotinic acetylcholine receptors, an endogenous inflammation‐resolving pathway, prevents TNFα‐induced NF‐κB activation, macrophage migration into the hippocampus, and cognitive decline following surgery.

Interpretation:

These data reveal the mechanisms for bidirectional communication between the brain and immune system following aseptic trauma. Pivotal molecular mechanisms can be targeted to prevent and/or resolve postoperative neuroinflammation and cognitive decline. ANN NEUROL 2011;70:986–995
Effect of silane treatment on physicochemical properties of lignocellulosic C. indica fiber
Authors: Singha A. S. , Rana Ashvinder K.
Published: October 2011

Present work deals with the mercerization of Cannabis indica fibers and their subsequent surface modification by aminopropyl triethoxysilane. The reaction parameters like time and concentration of the sodium hydroxide for mercerization were optimized. C. indica fibers treated with different silane concentration solutions were subjected to evaluation of some of their properties like swelling behavior in different solvents, moisture absorbance under different humidity levels, and resistance toward chemicals such as sodium hydroxide and hydrochloric acid. C. indica fibers treated with 2% aminopropyl triethoxysilane solution have been found more resistant toward moisture, water, and chemicals when compared with that of untreated fibers. Morphological, structural changes, thermal stability, and crystallinity of both silane treated and mercerized fibers have been studied by SEM, FTIR, TGA, and XRD techniques. Silane treatment has been found to cause decrease in crystallinity but increase in the thermal stability of the fibers. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
A comparison of new bone formation in patients with ankylosing spondylitis and patients with diffuse idiopathic skeletal hyperostosis: A retrospective cohort study over six years
Authors: Baraliakos X. , Listing J. , Buschmann J. , von der Recke A. , Braun J.
Published: October 2011

Objective

Ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) are both characterized by new bone formation in the spine but presumably have a different pathogenesis. This study was undertaken to compare the natural course of new bone formation in AS and DISH.

Methods

Lateral radiographs of the cervical and lumbar spine from AS and DISH patients obtained at ≥2 time points within 6 years were analyzed to quantify osteophyte development. Radiographs were scored in a blinded manner by 2 readers using the modified Stoke AS Spine Score (mSASSS). Bone spurs were categorized as having an angle of <45° or >45°.

Results

AS patients (n = 146) were younger than DISH patients (n = 141) (mean ± SD 54.2 ± 12.3 years versus 60.3 ± 7.7 years). Symptom duration (mean ± SD) was 23.6 ± 11.2 years in AS patients and 21.6 ± 12.4 years in DISH patients. The mSASSS at baseline was lower in DISH patients (mean ± SD 14.3 ± 6.7) than in AS patients (20.5 ± 14.5) but had increased by a similar amount at followup (3.3 ± 4.2 versus 4.1 ± 9.5). The mean mSASSS progression rate per year (1.3 units) was also comparable. The mean ± SD number of syndesmophytes per patient was higher in AS (5.7 ± 5.5) than DISH (2.7 ± 2.8) patients (P < 0.001), while degenerative bone spurs (mean ± SD) were more frequent in DISH (1.4 ± 1.8) than AS (1.0 ± 1.4) patients. AS patients developed more new bone spurs with an angle of <45° than >45° per patient (mean ± SD 2.1 ± 2.7 versus 0.6 ± 0.9) (P < 0.001), while similar amounts of both types of bone formation were seen in DISH patients.

Conclusion

Our findings indicate that the rates of new bone formation in AS and DISH are largely similar. Both groups show osteophyte development, but as expected, syndesmophytes are more frequent in AS patients while DISH patients have more degenerative bone spurs. The nature of the different mechanisms of bone formation needs further study.
Substance P and norepinephrine modulate murine chondrocyte proliferation and apoptosis
Authors: Opolka Alfred , Straub Rainer H. , Pasoldt Anja , Grifka Joachim , Grässel Susanne
Published: October 2011

Objective

Substance P (SP) and norepinephrine (NE) containing sensory and sympathetic nerve fibers innervate bone and fracture callus. They are involved in controlling vascularization and matrix differentiation during skeletal growth. Both types of nerve fibers are known to modulate growth and metabolic activity of osteoblasts and osteoclasts. The aim of this study was to understand the roles of SP and NE in chondrocyte metabolism and their impact on chondrocyte proliferation, apoptosis, and cell adhesion.

Methods

Primary costal chondrocytes were isolated from newborn mice. Micromass and monolayer cell culture regimens were used to analyze the effects of SP and NE on matrix formation, as determined by quantitative polymerase chain reaction and immunohistochemistry. The effects of SP and NE on proliferation, adhesion, and apoptosis of chondrocytes were determined by enzyme‐linked immunosorbent assay, bromodeoxyuridine, TUNEL, and morphometric analyses.

Results

SP, neurokinin type 1 (NK‐1) receptor, α‐adrenergic receptor (α‐AR), and β‐AR were abundantly expressed in primary costal chondrocytes. Stimulation with SP or NE did not affect extracellular matrix formation with respect to types I, II, and IX collagen and aggrecan in micromass pellets. SP dose‐dependently increased the rate of proliferation of chondrocytes via the NK‐1 receptor, whereas NE decreased the apoptosis rate of chondrocytes by stimulating β‐AR. Both neurotransmitters induced the formation of focal adhesion contacts.

Conclusion

Transmitters of sympathetic and sensory nerve fibers modulate the metabolic activity of chondrocytes. Endogenous SP, NK‐1 receptor, and adrenoceptor expression in chondrocytes implicates as‐yet‐unknown, presumably trophic, functions of neurotransmitter for skeletal growth and might be of interest for use in cartilage regenerative medicine.
Size and culture as determinants of the web policy of listed firms: The case of web accessibility in Western European countries
Authors: Lorca Pedro , Andrées Javier De , Martínez Ana B.
Published: October 2011

Web accessibility (WA) is an innovation in Web design; it can be considered as part of the corporate social responsibility (CSR) strategy of the firms. As adoption of innovations and CSR commitment are linked with firm size and national culture/legislation, we hypothesize that size and national culture/legislation, may have an effect on WA level. The authors studied an international sample made up of companies included in EUROSTOXX600 (The STOXX Europe 600 Index). The main results suggest that both size and culture have a significant effect on WA. Large firms as well as Anglo‐Saxon companies are more prone to have higher WA levels. A deeper analysis, which was done through the estimation of quantile regression equations, showed that the influence of size is significant for companies trying to excel or for those trying to avoid the worst WA. However, the effect of size is significant only in the lowest part of the conditional distribution.
The inconsistency of the h‐index
Authors: Waltman Ludo , van Eck Nees Jan
Published: October 2011

The h‐index is a popular bibliometric indicator for assessing individual scientists. We criticize the h‐index from a theoretical point of view. We argue that for the purpose of measuring the overall scientific impact of a scientist (or some other unit of analysis), the h‐index behaves in a counterintuitive way. In certain cases, the mechanism used by the h‐index to aggregate publication and citation statistics into a single number leads to inconsistencies in the way in which scientists are ranked. Our conclusion is that the h‐index cannot be considered an appropriate indicator of a scientist's overall scientific impact. Based on recent theoretical insights, we discuss what kind of indicators can be used as an alternative to the h‐index. We pay special attention to the highly cited publications indicator. This indicator has a lot in common with the h‐index, but unlike the h‐index it does not produce inconsistent rankings.
Basic properties of both percentile rank scores and the I3 indicator
Authors: Rousseau Ronald
Published: October 2011

We introduce the notions of congruous indicator of relative performance and congruous indicator of absolute performance. These notions are very similar to the notions of independence and consistency, yet slightly different. It is shown that percentile rank scores, as recently introduced by Leydesdorff, Bornmann, Mutz, and Opthof (2011), are strictly congruous indicators of relative performance, and similarly, that the Integrated Impact Indicator (I3), introduced by Leydesdorff and Bornmann (2011), is a strictly congruous indicator of absolute performance. Our analysis highlights the challenge of finding adequate axioms for ranking and for research evaluation.
Systematic review and meta-analysis of the use of lightweight versus heavyweight mesh in open inguinal hernia repair
Authors: Sajid M S , Leaver C , Baig M K , Sains P
Published: October 2011

Background

The objective of this study was systematically to analyse published randomized trials comparing lightweight mesh (LWM) with heavyweight mesh (HWM) in open inguinal hernia repair.

Methods

Randomized trials on LWM versus HWM were selected from the standard electronic databases. Reported outcomes were analysed systematically using RevMan. Pooled risk ratios were calculated for categorical outcomes, and mean differences for secondary continuous outcomes, using the fixed-effects and random-effects models for meta-analysis.

Results

Nine randomized trials containing 2310 patients were included. There was significant heterogeneity among trials. There was no difference in duration of operation, postoperative pain, recurrence rate, testicular atrophy and time to return to work between LWM and HWM groups. The two mesh types had a similar risk of perioperative complications, but LWM was associated with a reduced risk of developing chronic groin pain (risk ratio (RR) 0·61, 95 per cent confidence interval 0·50 to 0·74) and a reduced risk of developing other groin symptoms, such as stiffness and foreign body sensations (RR 0·64, 0·50 to 0·81).

Conclusion

The use of LWM for open inguinal hernia repair was not associated with an increased risk of hernia recurrence. LWM reduced the incidence of chronic groin pain as well as the risk of developing other groin symptoms. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
Transanal specimen extraction in robotic rectal cancer surgery
Authors: Kang J , Min B S , Hur H , Kim N K , Lee K Y
Published: October 2011

Background

The aim of this study was to identify the benefits of robotic transanal specimen extraction (RTSE) compared with minilaparotomy specimen extraction (MSE).

Methods

Patients who underwent totally robotic surgery with curative intent for treatment of adenocarcinoma of the rectum below 12 cm from the anal verge were selected from the authors' database. Patients were divided into RTSE and MSE groups according to the method of specimen delivery. Clinicopathological features and perioperative surgical outcomes were compared between the two groups.

Results

There were 53 patients in the RTSE group and 66 in the MSE group. No differences were observed in overall complications. Postoperative recovery was faster in the RTSE group in terms of resumption of a soft diet (mean(s.d.) 3·5(1·5) versus 4·6(1·7) days; P < 0·001) and length of hospital stay (9·0(4·8) versus 11·3(5·3) days; P = 0·016). Pain scores on a visual analogue scale were significantly lower in the RTSE group than in the MSE group from day 2 to day 5 after surgery (P = 0·021 to P < 0·001).

Conclusion

RTSE in robotic rectal cancer surgery was associated with less pain and a faster recovery than MSE. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
ChromiumSilicon Multiple Bonds: The Chemistry of Terminal N‐Heterocyclic‐Carbene‐Stabilized Halosilylidyne Ligands
Authors: Filippou Alexander C. , Chernov Oleg , Schnakenburg Gregor
Published: October 2011

An efficient method for the synthesis of the first N‐heterocyclic carbene (NHC)‐stabilized halosilylidyne complexes is reported that starts from SiBr4. In the first step, SiBr4 was treated with one equivalent of the N‐heterocyclic carbene 1,3‐bis[2,6‐bis(isopropyl)phenyl]imidazolidin‐2‐ylidene (SIdipp) to give the 4,5‐dihydroimidazolium salt [SiBr3(SIdipp)]Br (1‐Br), which then was reduced with potassium graphite to afford the silicon(II) dibromide–NHC adduct SiBr2(SIdipp) (2‐Br) in good yields. Heating 2‐Br with Li[CpCr(CO)3] afforded the complex [Cp(CO)2CrSiBr(SIdipp)] (3‐Br) upon elimination of CO. Complex 3‐Br features a trigonal‐planar‐coordinated silicon center and a very short CrSi double bond. Similarly, the reaction of SiCl2(SIdipp) (2‐Cl) with Li[CpCr(CO)3] gave the analogous chloro derivative [Cp(CO)2CrSiCl(SIdipp)] (3‐Cl). Complex 3‐Br undergoes an NHC exchange with 1,3‐dihydro‐4,5‐dimethyl‐1,3‐bis(isopropyl)‐2H‐imidazol‐2‐ylidene (IMe2iPr2) to give the complex [Cp(CO)2CrSiBr(IMe2iPr2)2] (4‐Br). Compound 4‐Br features a distorted‐tetrahedral four‐coordinate silicon center. Bromide abstraction occurs readily from 4‐Br with Li[B(C6F5)4] to give the putative silylidene complex salt [Cp(CO)2CrSi(IMe2iPr2)2][B(C6F5)4], which irreversibly dimerizes by means of an Si‐promoted electrophilic activation of one carbonyl oxygen atom to yield the dinuclear siloxycarbyne complex [Cp(CO)Cr{(μ‐CO)Si(IMe2iPr2)2}2‐ Cr(CO)Cp][B(C6F5)4]2 (5). All compounds were fully characterized, and the molecular structures of 2‐Br–5‐Br were determined by single‐crystal X‐ray diffraction. DFT calculations of 3‐Br and 3‐Cl and their carbene dissociation products [Cp(CO)2CrSiX] (X=Cl, Br) were carried out, and the electronic structures of 3‐Br, 3‐Cl and [Cp(CO)2CrSiX] were analyzed by the natural bond orbital method in combination with natural resonance theory.
Changes in Notch signaling coordinates maintenance and differentiation of the Drosophila larval optic lobe neuroepithelia
Authors: Weng Mo , Haenfler Jill M. , Lee Cheng‐Yu
Published: October 2011

A dynamic balance between stem cell maintenance and differentiation paces generation of post‐mitotic progeny during normal development and maintenance of homeostasis. Recent studies show that Notch plays a key role in regulating the identity of neuroepithelial stem cells, which generate terminally differentiated neurons that populate the adult optic lobe via the intermediate progenitor cell type called neuroblast. Thus, understanding how Notch controls neuroepithelial cell maintenance and neuroblast formation will provide critical insight into the intricate regulation of stem cell function during tissue morphogenesis. Here, we showed that a low level of Notch signaling functions to maintain the neuroepithelial cell identity by suppressing the expression of pointedP1 gene through the transcriptional repressor Anterior open. Increased Notch signaling, which coincides with transient cell cycle arrest but precedes the expression of PointedP1 in cells near the medial edge of neuroepithelia, defines transitioning neuroepithelial cells that are in the process of acquiring the neuroblast identity. Transient up‐regulation of Notch signaling in transitioning neuroepithelial cells decreases their sensitivity to PointedP1 and prevents them from becoming converted into neuroblasts prematurely. Down‐regulation of Notch signaling combined with a high level of PointedP1 trigger a synchronous conversion from transitioning neuroepithelial cells to immature neuroblasts at the medial edge of neuroepithelia. Thus, changes in Notch signaling orchestrate a dynamic balance between maintenance and conversion of neuroepithelial cells during optic lobe neurogenesis. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2012
Deficiency in crumbs homolog 2 (Crb2) affects gastrulation and results in embryonic lethality in mice
Authors: Xiao Zhijie , Patrakka Jaakko , Nukui Masatoshi , Chi Lijun , Niu Dadi , Betsholtz Christer , Pikkarainen Timo , Vainio Seppo , Tryggvason Karl
Published: October 2011

The Crumbs family of transmembrane proteins has an important role in the differentiation of the apical membrane domain in various cell types, regulating such processes as epithelial cell polarization. The mammalian Crumbs protein family is composed of three members. Here, we inactivated the mouse Crb2 gene with gene‐targeting techniques and found that the protein is crucial for early embryonic development with severe abnormalities appearing in Crb2‐deficient embryos at late‐gastrulation. Our findings indicate that the primary defect in the mutant embryos is disturbed polarity of the epiblast cells at the primitive streak, which affects epithelial to mesenchymal transition (EMT) during gastrulation, resulting in impaired mesoderm and endoderm formation, and embryonic lethality by embryonic day 12.5. These findings therefore indicate a novel role for the Crumbs family of proteins. Developmental Dynamics 240:2646–2656, 2011. © 2011 Wiley Periodicals, Inc.
Hyperactive BMP signaling induced by ALK2R206Hrequires type II receptor function in aDrosophilamodel for classic fibrodysplasia ossificans progressiva
Authors: Le Viet Q. , Wharton Kristi A.
Published: October 2011

Background:Fibrodysplasia Ossificans Progressiva (FOP) is an autosomal dominant disorder characterized by episodic deposition of heterotopic bone in place of soft connective tissue. All FOP‐associated mutations map to the BMP type I receptor, ALK2, with the ALK2R206Hmutant form found in the vast majority of patients. The mechanism(s) regulating the expressivity of hyperactive ALK2R206Hsignaling throughout a patient's life is not well understood.Results:InDrosophila, human ALK2R206Hreceptor induces hyperactive BMP signaling. As in vertebrates, elevated signaling associated with ALK2R206HinDrosophilais ligand‐independent. We found that a key determinant for ALK2R206Hhyperactivity is a functional type II receptor. Furthermore, our results indicate that like itsDrosophilaortholog, Saxophone (Sax), wild‐type ALK2 can antagonize, as well as promote, BMP signaling.Conclusions:The dual function of ALK2 is of particular interest given the heterozygous nature of FOP, as the normal interplay between such disparate behaviors could be shifted by the presence of ALK2R206Hreceptors. Our studies provide a compelling example forDrosophilaas a model organism to study the molecular underpinnings of complex human syndromes such as FOP. Developmental Dynamics 241:200–214, 2012. © 2011 Wiley Periodicals, Inc.
Oxidation versus Dioxygenation of Catechol: The Iron–Bispidine System
Authors: Comba Peter , Wadepohl Hubert , Wunderlich Steffen
Published: October 2011

The iron–bispidine‐catalyzed oxidation and dioxygenation (catechol dioxygenase activity) [i.e., the oxidation of 3,5‐di‐tert‐butylcatecholate (dbc2–) by [FeII(L)X2]n+ (L = 3,7‐dimethyl‐9‐oxo‐2,4‐bis(2‐pyridyl)‐3,7‐diazabicyclo[3.3.1]nonane‐1,5‐dicarboxylate methyl ester)] and air (O2) was studied experimentally and supported by the analysis of the X‐ray crystal structure of [Fe(L·MeOH)(tcc)][B(Ph)4] with the deactivated tetrachlorocatecholate tcc2– and a DFT‐based analysis. The [FeII(L)X2]n+/O2/dbc2– system catalyzes the intradiol cleavage of dbc2– but with a relatively low activity (5 % yield); most of the substrate is oxidized in a two‐electron oxidation to the benzoquinone (dbq) product (48 % yield). The crystallographic and DFT‐based theoretical analyses indicate that this is due to the high oxidation potential of the FeIII oxidant (fast and efficient electron transfer), that is, the oxidation to the benzoquinone side product is faster, and due to the bonding mode of the catecholate substrate to the FeIII oxidant, with little spin density transferred to the catecholate substrate.
Convergent Preparation of DimLex Hexasaccharide Analogues
Authors: Hendel Jenifer L. , Auzanneau France‐Isabelle
Published: October 2011

We report the convergent preparation of four hexasaccharides to be used towards the synthesis of a safe anticancer vaccine based on the tumor‐associated carbohydrate antigen dimLex. A common trisaccharide intermediate was first synthesized as a precursor to the tetrasaccharide backbones. These tetrasaccharides were then converted into diol acceptors and fucosylated at O‐3 of both glucosamine residues. The conditions required to promote fucosylation at O‐3 of the reducing end glucosamine units led to some loss of the fucosyl units already introduced at O‐3 of the nonreducing end glucosamine residues. Despite this hurdle, optimization of the glycosylation conditions provided the desired hexasaccharides in sufficient quantities to prepare the final analogues. Propyl glycosides and cysteamine adducts were prepared easily in two steps from the protected allyl glycoside hexasaccharides, and a one‐step deprotection under metal‐dissolving conditions was key to our deprotection strategy.
Microfluidic devices with disposable enzyme electrode for electrochemical monitoring of glucose concentrations
Authors: Li Xin , Zhang Fan , Shi Jian , Wang Li , Tian Jing‐Hua , Zhou Xiong‐Tu , Jiang Lian‐Mei , Liu Li , Zhao Zhen‐Jie , He Pin‐Gang , Chen Yong
Published: October 2011

This article describes the fabrication of tube‐like microchannels made of UV curable polymer on a glass substrate and the device assembling with a disposable enzyme‐working electrode for high‐sensitivity electrochemical detection. While both reference and counter electrodes are patterned on the surface of the glass substrate, the working electrode is flipped on the top of the channel with an open access, providing a face‐to‐face probing configuration. When the enzyme electrode is contaminated or degraded, it can be easily replaced by a new one, keeping the main body of the device and the detection schema unchanged. Using glucose oxidase‐coated gold electrodes, we were able to determine a linear amperometry response to the glucose concentrations in the range of 2–16 mM. By replacing the as‐prepared working electrode by the one after thermal treatments, we showed a much more degraded enzyme electrode activity, enabling efficient determination of the electrode quality as well as the whole process optimization.
Integration of microchip electrophoresis with electrochemical detection using an epoxy‐based molding method to embed multiple electrode materials
Authors: Johnson Alicia S. , Selimovic Asmira , Martin R. Scott
Published: October 2011

This paper describes the use of epoxy‐encapsulated electrodes to integrate microchip‐based electrophoresis with electrochemical detection. Devices with various electrode combinations can easily be developed. This includes a palladium decoupler with a downstream working electrode material of either gold, mercury/gold, platinum, glassy carbon, or a carbon fiber bundle. Additional device components such as the platinum wires for the electrophoresis separation and the counter electrode for detection can also be integrated into the epoxy base. The effect of the decoupler configuration was studied in terms of the separation performance, detector noise, and the ability to analyze samples of a high ionic strength. The ability of both glassy carbon and carbon fiber bundle electrodes to analyze a complex mixture was demonstrated. It was also shown that a PDMS‐based valving microchip can be used along with the epoxy‐embedded electrodes to integrate microdialysis sampling with microchip electrophoresis and electrochemical detection, with the microdialysis tubing also being embedded in the epoxy substrate. This approach enables one to vary the detection electrode material as desired in a manner where the electrodes can be polished and modified as is done with electrochemical flow cells used in liquid chromatography.
Lysosomal exocytosis in Schwann cells contributes to axon remyelination
Authors: Chen Gang , Zhang Zhijun , Wei Zhongya , Cheng Qiong , Li Xia , Li Wei , Duan Shumin , Gu Xiaosong
Published: October 2011

Myelin biogenesis is a complex process involving coordinated exocytosis, endocytosis, mRNA transport, and cytoskeletal dynamics. Although abnormalities of myelin are common in lysosomal storage diseases, our understanding of the role of lysosomes in the formation and maintenance of myelin is still limited. Here, we show that late endosomes/lysosomes in Schwann cells contain abundant myelin protein P0, which accounts for over half the total protein of compact myelin in the peripheral nervous system and exhibit Ca2+‐dependent exocytosis in response to various stimuli. Downregulation of Rab27a, a small GTPase required for the trafficking of the secretory lysosomes to the plasma membrane, largely blocked lysosomal exocytosis in Schwann cells and reduced the remyelination of regenerated sciatic nerve. These findings highlight a novel role for lysosomes in Schwann cells and suggest that the regulated lysosome exocytosis in Schwann cells may have important physiological and pathological significance in the peripheral nervous system. © 2011 Wiley Periodicals, Inc.
Near and far space: Understanding the neural mechanisms of spatial attention
Authors: Lane Alison R. , Ball Keira , Smith Daniel T. , Schenk Thomas , Ellison Amanda
Published: October 2011

Visuospatial neglect is a multicomponent syndrome, and one dissociation reported is between neglect for near (peripersonal) and far (extrapersonal) space. Owing to patient heterogeneity and extensive lesions, it is difficult to determine the precise neural mechanisms underlying this dissociation using clinical methodology. In this study, transcranial magnetic stimulation was used to examine the involvement of three areas in the undamaged brain, while participants completed a conjunction search task in near and far space. The brain areas investigated were right posterior parietal cortex (rPPC), right frontal eye field (rFEF), and right ventral occipital cortex (rVO), each of which has been implicated in visuospatial processing. The results revealed a double dissociation, whereby rPPC was involved for search in near space only, whilst rVO only became necessary when the task was completed in far space. These data provide clear evidence for a dorsal and ventral dissociation between the processing of near and far space, which is compatible with the functional roles previously attributed to the two streams. For example, the involvement of the dorsal stream in near space reflects its role in vision for action, because it is within this spatial location that actions can be performed. The results also revealed that rFEF is involved in the processing of visual search in both near and far space and may contribute to visuospatial attention and/or the control of eye‐movements irrespective of spatial frame. We discuss our results with respect to their clear ramifications for clinical diagnosis and neurorehabilitation. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Human papillomavirus infection in women with and without cervical cancer in Tehran, Iran
Authors: Khodakarami Nahid , Clifford Gary M. , Yavari Parvin , Farzaneh Farah , Salehpour Saghar , Broutet Natalie , Bathija Heli , Heideman Daniëlle A.M. , van Kemenade Folkert J. , Meijer Chris J.L.M. , Hosseini Seyed Jalil , Franceschi Silvia
Published: October 2011

No data exist on the population prevalence of, or risk factors for, human papillomavirus (HPV) infection in Iran or the Middle East. Cervical specimens were obtained from 825 married women aged 18–59 years from the general population of Tehran, Iran and from 45 locally diagnosed invasive cervical cancers (ICC) according to the standardized protocol of the International Agency for Research on Cancer HPV Prevalence Surveys. HPV was detected and genotyped using a GP5+/6+ PCR‐based assay. HPV prevalence in the general population was 7.8% (95% confidence interval: 6.0–9.8) (5.1% of high‐risk types), with no significant variation by age. HPV positivity was significantly higher among divorced women, women in polygamous marriages and those reporting husband's absence from home for >7 nights/month. HPV16/18 accounted for 30 and 82.2% of HPV‐positive women in the general population and ICC, respectively. Cervical cancer prevention policies should take into account the relatively low HPV prevalence in this population.
α‐Tocopheryloxyacetic acid is superior to α‐tocopheryl succinate in suppressing HER2‐high breast carcinomas due to its higher stability
Authors: Dong Lan‐Feng , Grant Gary , Massa Helen , Zobalova Renata , Akporiaye Emmanuel , Neuzil Jiri
Published: October 2011

Breast cancer is the number one neoplastic disease of women, with the HER2‐high carcinomas presenting a considerable challenge for efficient treatment. Therefore, a search for novel agents active against this type of cancer is warranted. We tested two vitamin E (VE) analogs, the esterase‐hydrolyzable α‐tocopheryl succinate (α‐TOS) and the non‐hydrolyzable ether α‐tocopheryloxyacetic acid (α‐TEA) for their effects on HER2‐positive breast carcinomas using a breast tumor mouse model and breast cancer cell lines. Ultrasound imaging documented that α‐TEA suppressed breast carcinomas in the transgenic animals more efficiently than found for its ester counterpart. However, both agents exerted a comparable apoptotic effect on the NeuTL breast cancer cells derived from the FVB/N c‐neu mice as well as in the human MBA‐MD‐453 and MCF7HER2‐18 cells with high level of HER2. The superior anti‐tumor effect of α‐TEA over α‐TOS in vivo can be explained by longer persistence of the former in mice, possibly due to the enhanced plasma and hepatic processing of α‐TOS in comparison to the esterase‐non‐cleavable α‐TEA. Indeed, the stability of α‐TOS in plasma was inferior to that of α‐TEA. We propose that α‐TEA is a promising drug efficient against breast cancer, as documented by its effect on experimental HER2‐positive breast carcinomas that present a considerable problem in cancer management.
Survival in patients with human papillomavirus positive tonsillar cancer in relation to treatment
Authors: Attner Per , Näsman Anders , Du Juan , Hammarstedt Lalle , Ramqvist Torbjörn , Lindholm Johan , Munck‐Wikland Eva , Dalianis Tina , Marklund Linda
Published: October 2011

The incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases have increased in the last decades. In parallel, treatment for tonsillar cancer has been intensified e.g., by accelerated radiotherapy, and chemotherapy, resulting in more side effects. Patients with HPV‐positive tonsillar cancer have better prognosis than those with HPV‐negative tumors, and the former group could hypothetically benefit from reduced, less‐toxic treatment without compromising survival. Here, we therefore evaluated possible differences in overall and disease‐specific survival after different oncological treatments in 153 patients with HPV DNA‐ and P16‐positive tonsillar cancer who were diagnosed and treated with intent to cure between 2000 and 2007, in Stockholm, Sweden. Of these patients, 86 were treated with conventional radiotherapy, 40 were treated with accelerated radiotherapy and 27 were treated with chemoradiotherapy. There were no significant differences in overall or disease‐free survival between the groups. However, there was a trend, implying a beneficial effect of the intensified treatment, with chemoradiotherapy being better than radiotherapy despite that more patients had stage IV disease in the former group; and accelerated radiotherapy being better than conventional radiotherapy. This needs to be followed further in larger more homogenous groups of patients. In conclusion, patients with HPV‐positive tonsillar cancer treated with conventional‐ or accelerated radiotherapy or chemoradiotherapy disclosed similar survival rates. The trend for better survival and less metastasis after intensified treatment underlines the need for large prospective studies comparing less intense to more intense treatment (chemoradiotherapy).
Food‐frequency questionnaire‐based estimates of total antioxidant capacity and risk of non‐Hodgkin lymphoma
Authors: Holtan Shernan G. , O'Connor Helen M. , Fredericksen Zachary S. , Liebow Mark , Thompson Carrie A. , Macon William R. , Micallef Ivana N. , Wang Alice H. , Slager Susan L. , Habermann Thomas M. , Call Timothy G. , Cerhan James R.
Published: October 2011

Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non‐Hodgkin lymphoma (NHL). The oxygen radical absorbance capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food‐frequency questionnaire (FFQ). We tested the hypothesis that higher intake of antioxidant nutrients from foods, supplements and FFQ‐based ORAC values are associated with a lower risk of NHL in a clinic‐based study of 603 incident cases and 1,007 frequency‐matched controls. Diet was assessed with a 128‐item FFQ. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals adjusted for age, sex, residence and total energy. Dietary intake of α‐tocopherol (OR = 0.50; p‐trend = 0.0002), β‐carotene (OR = 0.58; p‐trend = 0.0005), lutein/zeaxanthin (OR = 0.62; p‐trend = 0.005), zinc (OR = 0.54; p‐trend = 0.003) and chromium (OR = 0.68; p‐trend = 0.032) was inversely associated with NHL risk. Inclusion of supplement use had little impact on these associations. Total vegetables (OR = 0.52; p‐trend < 0.0001), particularly green leafy (OR = 0.52; p‐trend<0.0001) and cruciferous (OR = 0.68; p‐trend = 0.045) vegetables, were inversely associated with NHL risk. NHL risk was inversely associated with both hydrophilic ORAC (OR = 0.61, p‐trend = 0.003) and lipophilic ORAC (OR = 0.48, p‐trend = 0.0002), although after simultaneous adjustment for other antioxidants or total vegetables, only the association for lipophilic ORAC remained significant. There was no striking heterogeneity in results across the common NHL subtypes. Higher antioxidant intake as estimated by the FFQ‐ORAC, particularly the lipophilic component, was associated with a lower NHL risk after accounting for other antioxidant nutrients and vegetable intake, supporting this as potentially useful summary measure of total antioxidant intake.
Tumor TP53 expression status, body mass index and prognosis in colorectal cancer
Authors: Morikawa Teppei , Kuchiba Aya , Liao Xiaoyun , Imamura Yu , Yamauchi Mai , Qian Zhi Rong , Nishihara Reiko , Sato Kaori , Meyerhardt Jeffrey A. , Fuchs Charles S. , Ogino Shuji
Published: October 2011

Inactivation of the TP53 (p53) pathway by TP53 mutations is one of key steps in colorectal carcinogenesis. TP53 also plays an important role in cellular energy metabolism. We hypothesized that TP53‐altered tumor cells might behave aggressively independent of energy balance, while progression of TP53‐intact cells might depend on excess energy balance. Utilizing a database of 1,060 colon and rectal cancer patients in two prospective cohort studies, we evaluated TP53 expression by immunohistochemistry. Among 1,060 colorectal cancers, 457 (43%) tumors were positive for TP53. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, the CpG island methylator phenotype, LINE‐1 methylation, KRAS, BRAF and PIK3CA. TP53 positivity was not significantly associated with cancer‐specific survival in univariate analysis with HR of 1.16 [95% confidence interval (CI) = 0.92–1.45], which became significant after stage adjustment (multivariate HR = 1.30; 95% CI = 1.02–1.65). Notably, we found a possible modifying effect of patient's body mass index (BMI) on tumor TP53. In non‐obese patients (BMI < 30 kg/m2), TP53 positivity was associated with shorter cancer‐specific survival (multivariate HR = 1.53; 95% CI = 1.17‐2.00), while TP53 positivity was not significantly associated with survival among obese patients (BMI ≥30 kg/m2). Effect of TP53 positivity on cancer‐specific survival significantly differed by BMI (pinteraction = 0.0051). The adverse effect of obesity on patient mortality was limited to TP53‐negative patients. These molecular pathological epidemiology data may support a dual role of TP53 alterations in cell‐cycle deregulation and cell autonomy with respect to energy balance status.
Benzothiophene carboxamide derivatives as novel antimalarials
Authors: Banerjee Tanushree , Kapoor Neha , Surolia Namita , Surolia Avadhesha
Published: October 2011

Bromo‐benzothiophene carboxamide derivatives have been shown in the preceding article to inhibit Plasmodium falciparum Enoyl‐ACP reductase. Here, we report bromo‐benzothiophene carboxamide derivatives as potent inhibitors of Plasmodium asexual blood‐stages in vitro as well as in vivo in the mouse model. These compounds specifically impair the development of metabolically active trophozoite stage of intraerythrocytic cycle and the intravenous administration of 3‐bromo‐N‐(4‐fluorobenzyl)‐benzo[b]thiophene‐2‐carboxamide (compound 6) enhances the longevity of P. berghei infected mice by 2 weeks compared to disease control animals thereby preventing the onset of ataxia and convulsions in treated mice. These compounds thus hold promise for the development of potent antimalarials. © 2011 IUBMB IUBMB Life, 63(12): 1111–1115, 2011
Immobilized thermolysin for highly efficient production of low‐molecular‐weight protamine—An attractive cell‐penetrating peptide for macromolecular drug delivery applications
Authors: David Allan E. , Gong Junbo , Chertok Beata , Domszy Roman C. , Moon Cheol , Park Yoon Shin , Wang Nam Sun , Yang Arthur J. , Yang Victor C.
Published: October 2011

Macromolecules present a remarkable potential as future therapeutics. However, their translation into clinical practice has been hampered by an inherently low bioavailability. Cell‐penetrating peptides (CPP) have been recently shown to significantly improve on the bioavailability of macromolecules. Yet, the high cost associated with development and production of these peptides is a major factor hindering their rapid deployment beyond the laboratory. Here, we describe a facile and robust methodology for efficient and large‐scale production of low‐molecular‐weight protamine—a potent CPP of great clinical potential. Our methodology is based on the immobilization of thermolysin, an enzyme catalyzing digestion of native protamine, on chemically surface‐modified gels produced by silica sol–gel chemistry. Thermolysin was immobilized at extremely high matrix loading of 733 mg/g matrix and exhibited good thermal and pH stability, indicating robustness with respect to processing conditions. The mechanical properties of the silica matrix further allowed utilization of the immobilized thermolysin in both batch and packed‐bed reactor systems to produce the LMWP peptide in high yields. Results presented here are of high significance as this efficient and cost‐effective production of high purity LMWP could enable clinical translation of many potential macromolecular drugs. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
In vitro differentiation and biocompatibility of mesenchymal stem cells on a novel platelet releasate‐containing injectable composite
Authors: McCanless Jonathan D. , Jennings Lisa K. , Cole Judith A. , Bumgardner Joel D. , Haggard Warren O.
Published: October 2011

Underlying changes in subchondral and cancellous bone precede joint degeneration in spinal discs, knees, hips, and other joints. We hypothesize that an early bone remodeling intervention therapy may alleviate or postpone the later manifestation of joint failure. Utilization of a novel biomaterial for injection deliverability to the underlying subchondral and cancellous bone during the onset of osseous changes, before severe cartilaginous damage, is proposed. In this preliminary study, we introduced novel platelet releasate‐containing alginate/calcium phosphate composites for this intervention therapy and evaluated them in vitro through mesenchymal stem cell biocompatibility and induction of osteochondral differentiation. DNA quantification and gene expression profiles suggested mesenchymal stem cells were directed along an osteochondral differentiation pathway, more specifically, to the immature nonhypertrophic chondrocyte phenotype. These conclusions were based on reduced mitogenic activity, a rapid upregulation followed by suppression of Runx2 transcription factor mRNA, sustained upregulation of Sox9 transcription factor mRNA and the absence of late marker expressions for both mature articular chondrocytes and osteoblasts over the course of 14 days. Initial findings in regard to the use of these materials for bone remodeling were positive and support the execution of future studies evaluating the inflammatory and angiogenic aspects of the materials. In this study, we have considered one of the many aspects of the endochondral ossification process; neovascularization and resorption of bone with an irregular physiology need to be evaluated. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
The association between deployment‐related posttraumatic growth among U.S. army soldiers and negative behavioral health conditions
Authors: Gallaway M. Shayne , Millikan Amy M. , Bell Michael R.
Published: October 2011

Objectives: This study assessed posttraumatic growth (PTG) in a sample of U.S. Army Soldiers using the Post‐Traumatic Growth Inventory (PTGI), and the relationship between PTG and negative behavioral health (BH) conditions. Design: A sample of Soldiers with prior combat deployment experience (n = 1,834) completed an anonymous survey including demographics, the PTGI, and negative BH conditions. Results: Among previously deployed Soldiers, those reporting the highest number of combat experiences also reported significantly higher overall PTG. A significant inverse relationship was observed between PTG and recent suicidal ideation, whereby Soldiers reporting recent suicidal ideation reported significantly lower overall PTG. Conclusions: This study quantified PTG resulting from deployment and demonstrated the degree to which combat experiences might result in PTG. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–10, 2011.
Comparing the pulmonary embolism severity index and the prognosis in pulmonary embolism scores as risk stratification tools
Authors: Chan Chee M. , Woods Christian J. , Shorr Andrew F.
Published: October 2011

BACKGROUND:

Multiple risk stratification scoring systems exist to forecast outcomes in patients with acute pulmonary embolism (PE).

OBJECTIVE:

We evaluated the comparative validity of the PE severity index (PESI) and the prognosis in pulmonary embolism (PREP) scores to predict mortality in acute PE.

DESIGN:

Retrospective observational cohort study.

SETTING:

Washington Hospital Center, Washington, DC.

PATIENTS:

Consecutive adults (aged >18 years) diagnosed with acute PE.

INTERVENTION:

The PESI and PREP scores were calculated.

MEASUREMENTS:

Raw PESI scores were segregated into risk class (I‐V) and then dichotomized into low (I‐II) versus high (III‐V) risk groups; the raw PREP scores were divided into low (0‐7) versus high (>7) risk groups. The primary endpoint was 30‐day and 90‐day mortality. We determined the negative predictive value and computed the area under the receiver operating characteristics (AUROC) curves to compare the ability of these scoring tools.

RESULTS:

The cohort consisted of 302 subjects. Thirty‐day mortality was 3.0%, and 4.0% died within 90 days. The PESI and the PREP performed similarly (PESI AUROC: 0.858 [95% confidence interval (CI), 0.773‐0.943] vs 0.719 [95% CI, 0.563‐0.875] for PREP). Segregating these scores into risk categories did not affect their discriminatory power (AUROC: 0.684 [95% CI, 0.559‐0.810] for PESI and 0.790 [95% CI, 0.679‐0.903] for PREP). The negative predictive value for death of being classified as low risk by the PESI or PREP was 100% and 99%, respectively.

CONCLUSIONS:

The PREP score performed comparably to the PESI score for identifying PE patients at low risk for short‐term and intermediate‐term mortality. Journal of Hospital Medicine 2011;. © 2011 Society of Hospital Medicine
Inpatient insulin orders: Are patients getting what is prescribed?
Authors: Deal Eli N. , Liu Aiqun , Wise Laura L. , Honick Kathy A. , Tobin Garry S.
Published: October 2011

BACKGROUND:

In‐hospital insulin administration is associated with many medication errors, but the frequency and reasons for insulin administration errors are poorly described. To document types and frequency of errors related to insulin administration, an examination of 4 units was conducted.

METHODS:

Using snapshot methodology, 4 non‐intensive care unit (ICU) areas (medicine, cardiology, transplant, and surgery) were examined in an observational, prospective manner for 4 weeks. Each patient on insulin on the first day was followed for 7 days. Definitions and error categories were defined prior to data collection. Error types and numbers were collected and quantified on per‐day or per‐patient basis.

RESULTS:

A total of 116 patient audit periods covering a total of 378 inpatient hospital days were examined. Inpatient insulin regimens on day 1 included correctional insulin only (51.7% of cases), neutral protamine Hagedorn ([NPH] 12%), and glargine (28.4%). A total of 199 administration errors occurred at a rate of 1.72 errors/patient‐period and 0.53 errors/patient day. Missing documentation of doses (15.5% of all patients) and insulin being held without an order (25% of patients) were the most frequently occurring events. Other errors include transcription (7.5%), timing errors (22.7%), and lack of documentation of physician notification of hypoglycemia (12.6%).

CONCLUSIONS:

Errors associated with insulin in the hospital are common and reveal a number of system errors that should be addressed. These data provide a foundation for future performance improvement. Journal of Hospital Medicine 2011;. © 2011 Society of Hospital Medicine