bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA silencing of tumor suppressor DLC-1 promotes efficient hepatitis C virus replication in primary human hepatocytes
Authors: Banaudha Krishna , Kaliszewski Michael , Korolnek Tamara , Florea Liliana , Yeung Man Lung , Jeang Kuan-Teh , Kumar Ajit
Published: September 2010

MicroRNAs (miRNAs) are approximately 22-nucleotide noncoding RNAs that constitute silencers of target gene expression. Aberrant expression of miRNA has been linked to a variety of cancers, including hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) infection is considered a major cause of chronic liver disease and HCC, although the mechanism of virus infection–associated hepatocarcinogenesis remains unclear. We report a direct role of miRNAs induced in HCV-infected primary human hepatocytes that target the tumor suppressor gene DLC-1 (a Rho GTPase-activating protein), which is frequently deleted in HCC, and other solid human tumors. MicroRNA miR-141 that targets DLC-1 was accentuated in cells infected with HCV genotypes 1a, 1b, and 2a. We present several lines of evidence that efficient HCV replication requires miR-141–mediated suppression of DLC-1. An increase in miR-141 correlated with the inhibition of DLC-1 protein in HCV-infected cells. Depletion of miR-141 with oligonucleotides complementary to the miRNAs inhibited virus replication, whereas artificially increased levels of intracellular miR-141 enhanced HCV replication. HCV-infected hepatocytes showed enhanced cell proliferation that can be countered by overexpression of DLC-1.

Conclusion:

The collective results of this study suggest a novel mechanism of HCV infection–associated miRNA-mediated regulation of a tumor suppressor protein that has the ability to influence cell proliferation and HCV infection–mediated liver cancer. (Hepatology 2011)
Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians
Authors: Stickel Felix , Buch Stephan , Lau Katharina , zu Schwabedissen Henriette Meyer , Berg Thomas , Ridinger Monika , Rietschel Marcella , Schafmayer Clemens , Braun Felix , Hinrichsen Holger , Günther Rainer , Arlt Alexander , Seeger Marcus , Müller Sebastian , Seitz Helmut Karl , Soyka Michael , Lerch Markus , Lammert Frank , Sarrazin Christoph , Kubitz Ralf , Häussinger Dieter , Hellerbrand Claus , Bröring Dieter , Schreiber Stefan , Kiefer Falk , Spanagel Rainer , Mann Karl , Datz Christian , Krawczak Michael , Wodarz Norbert , Völzke Henry , Hampe Jochen
Published: September 2010

A recent genome-wide study revealed an association between variation in the

PNPLA3

gene and liver fat content. In addition, the

PNPLA3

single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79;

P

genotype = 1.2 × 10−5;

P

allelic = 1.6 × 10−6) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33;

P

genotype = 0.0085;

P

allelic = 0.0042). The latter, biochemically defined association was confirmed in an independent population-based cohort of at-risk drinkers with a median alcohol intake of 300 g/week (OR 4.75;

P

genotype = 0.040;

P

allelic = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele

PNPLA3

rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (

P

combined = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele

PNPLA3

rs738409(G) was estimated at 26.6%.

Conclusion:

Genotype

PNPLA3

rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians. (Hepatology 2011)
Enteric dysbiosis associated with a mouse model of alcoholic liver disease
Authors: Yan Arthur W. , Fouts Derrick E. , Brandl Johannes , Stärkel Peter , Torralba Manolito , Schott Eckart , Tsukamoto Hide , Nelson Karen E. , Brenner David A. , Schnabl Bernd
Published: September 2010

The translocation of bacteria and bacterial products into the circulation contributes to alcoholic liver disease. Intestinal bacterial overgrowth is common in patients with alcoholic liver disease. The aims of our study were to investigate bacterial translocation, changes in the enteric microbiome, and its regulation by mucosal antimicrobial proteins in alcoholic liver disease. We used a mouse model of continuous intragastric feeding of alcohol or an isocaloric diet. Bacterial translocation occurred prior to changes observed in the microbiome. Quantitative changes in the intestinal microflora of these animals were assessed first using conventional culture techniques in the small and large intestine. Although we found no difference after 1 day or 1 week, intestinal bacterial overgrowth was observed in the gastrointestinal tract of mice fed alcohol for 3 weeks compared with control mice fed an isocaloric liquid diet. Because <20% of all gastrointestinal bacteria can be cultured using conventional methodologies, we performed massively parallel pyrosequencing to further assess the qualitative changes in the intestinal microbiome following alcohol exposure. Sequencing of 16S ribosomal RNA genes revealed a relative abundance of Bacteroidetes and Verrucomicrobia bacteria in mice fed alcohol compared with a relative predominance of Firmicutes bacteria in control mice. With respect to the host's transcriptome, alcohol feeding was associated with down-regulation in gene and protein expression of bactericidal c-type lectins Reg3b and Reg3g in the small intestine. Treatment with prebiotics partially restored Reg3g protein levels, reduced bacterial overgrowth, and lessened alcoholic steatohepatitis.

Conclusion:

Alcohol feeding is associated with intestinal bacterial overgrowth and enteric dysbiosis. Intestinal antimicrobial molecules are dysregulated following chronic alcohol feeding contributing to changes in the enteric microbiome and to alcoholic steatohepatitis. (Hepatology 2011)
Effects of hippocampal high‐frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats
Authors: Luna‐Munguía Hiram , Meneses Alfredo , Peña‐Ortega Fernando , Gaona Andres , Rocha Luisa
Published: September 2010

Hippocampal high frequency electrical stimulation (HFS) at 130 Hz has been proposed as a therapeutical strategy to control neurological disorders such as intractable temporal lobe epilepsy (TLE). This study was carried out to determine the effects of hippocampal HFS on the memory process and the probable involvement of amino acids. Using the autoshaping task, we found that animals receiving hippocampal HFS showed augmented short‐term, but not long‐term memory formation, an effect blocked by bicuculline pretreatment and associated with enhanced tissue levels of amino acids in hippocampus. In addition, microdialysis experiments revealed high extracellular levels of glutamate, aspartate, glycine, taurine, and alanine during the application of hippocampal HFS. In contrast, GABA release augmented during HFS and remained elevated for more than 1 h after the stimulation was ended. HFS had minimal effects on glutamine release. The present results suggest that HFS has an activating effect on specific amino acids in normal hippocampus that may be involved in the enhanced short‐term memory formation. These data further provide experimental support for the concept that hippocampus may be a promising target for focal stimulation to treat intractable seizures in humans. © 2010 Wiley Periodicals, Inc., Inc.
Hippocampal contributions to the episodic simulation of specific and general future events
Authors: Addis Donna Rose , Cheng Theresa , P. Roberts Reece , Schacter Daniel L.
Published: September 2010

Recent studies have demonstrated that remembering past experiences and imagining future scenarios recruits a core network including the hippocampus. Even so, constructing future events engages the hippocampus more than remembering past events. This fMRI study examined whether increased hippocampal activity for future events includes both specific and general events. Participants constructed specific and general past and future events during fMRI scanning. We replicated previous findings of increased activity in the right anterior hippocampus when constructing future relative to past events, and when constructing specific relative to general events. Importantly, both effects were driven by a significant interaction between temporal direction and specificity, with specific future events resulting in more activity than other conditions, including general future events. No regions exhibited greater activity during the construction of past relative to future events, or general relative to specific events. These results suggest that the process of constructing a detailed representation of a novel and specific future event differentially engages the right anterior hippocampus compared with other forms of event simulation and recall. Future work is needed to disambiguate the role of encoding, novelty and detail recombination in engaging the right anterior hippocampus during simulation. © 2010 Wiley‐Liss, Inc.
High susceptibility to azoxymethane‐induced colorectal carcinogenesis in obese KK‐Ay mice
Authors: Teraoka Naoya , Mutoh Michihiro , Takasu Shinji , Ueno Toshiya , Nakano Katsuya , Takahashi Mami , Imai Toshio , Masuda Shuichi , Sugimura Takashi , Wakabayashi Keiji
Published: September 2010

Obesity is associated with colon carcinogenesis. However, not much information is available regarding the mechanisms of obesity‐associated colorectal cancer, and there are only few useful animal models for investigating the underlying mechanism between obesity and colorectal cancer. KK‐Ay mice exhibit severe obesity. Amount of visceral fat assessed by micro‐computed tomography was almost 15 times higher than that of same aged C57BL/6J mice. Treatment with azoxymethane (AOM; 200 μg/mouse injected once a week for 3 times) resulted in markedly increased colon aberrant crypt foci (ACF) development (≈70 ACF/mouse) in KK‐Ay mice compared with lean C57BL/6J mice (≈9 ACF/mouse). Moreover, administration of AOM at a dose of 200 μg/mouse once a week for 6 times developed colorectal adenocarcinomas within only 7 weeks after the last AOM injection. The incidence of adenocarcinoma was 88% in KK‐Ay mice and was markedly higher than the 4% observed in C57BL/6J mice. The number of tumors/mouse was 7.80 in KK‐Ay mice and also markedly higher than the 0.12 in the C57BL/6J case. Interestingly, adenocarcinomas were observed in most of the AOM‐treated KK‐Ay mice along with remarkable tumor angiogenesis, and some showed submucosal invasion. These results indicate that the KK‐Ay mouse, featuring intact leptin and leptin receptor Ob‐Rbl, could be a useful animal model to investigate obesity‐associated cancer.
In vivo study of the effect of mechanical compression on formation of OCT images of human skin
Authors: Kirillin Mikhail Yu. , Agrba Pavel D. , Kamensky Vladislav A.
Published: September 2010

Modern optical diagnostic techniques often require deformations of the studied biotissues for image acquisition. This paper discusses the effect of mechanical compression on the formation of OCT images of human skin. The study was performed in vivo on human volunteers of different age. We show that application of compression to human skin induces changes in optical properties of the sample associated with elasticity of different skin layers. These changes induce an increase in the contrast of interlayer boundaries. Further application of compression causes the appearance of dark areas in the OCT images obtained, likely associated with interstitial or intracellular water inflow to the observed region. The effects studied are of importance for proper interpretation of obtained OCT images in diagnosis of skin pathologies. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantitative BOLD: The effect of diffusion
Authors: Dickson John D. , Ash Tom W.J. , Williams Guy B. , Harding Sally G. , Carpenter T. Adrian , Menon David K. , Ansorge Richard E.
Published: September 2010

Purpose:

To make the quantitative blood oxygenation level‐dependent (qBOLD) method more suitable for clinical application by accounting for proton diffusion and reducing acquisition times.

Materials and Methods:

Monte Carlo methods are used to simulate the signal from diffusing protons in the presence of a blood vessel network. A diffusive qBOLD model was then constructed using a lookup table of the results. Acquisition times are reduced by parallel imaging and by employing an integrated fieldmapping method, rather than running an additional sequence.

Results:

The addition of diffusion to the model is shown to have a significant impact on predicted signal formation. This is found to affect all fitted parameters when the model is applied to real data. Parallel imaging and integrated fieldmapping allowed the GESSE (gradient echo sampling of a spin echo) acquisition to be made in less than 10 minutes while maintaining high signal‐to‐noise ratio (SNR).

Conclusion:

By incorporating integrated field mapping and parallel imaging techniques, GESSE data were acquired within clinically acceptable acquisition times. These data fit closely to the diffusive qBOLD model, providing more realistic and robust measurements of T2 and blood oxygenation than the static model. J. Magn. Reson. Imaging 2010;32:953–961. © 2010 Wiley‐Liss, Inc.
Device for sectioning prostatectomy specimens to facilitate comparison between histology and in vivo MRI
Authors: Drew Bryn , Jones Edward C. , Reinsberg Stefan , Yung Andrew C. , Goldenberg S. Larry , Kozlowski Piotr
Published: September 2010

Purpose

To develop a device for sectioning prostatectomy specimens that would facilitate comparison between histology and in vivo MRI.

Materials and Methods

A multi‐bladed cutting device was developed, which consists of an adjustable box capable of accommodating a prostatectomy specimen up to 85 mm in size in the lateral direction, a “plunger” tool to press on the excised gland from the top to prevent it from rolling or sliding during sectioning, and a multi‐bladed knife assembly capable of holding up to 21 blades at 4‐mm intervals. The device was tested on a formalin fixed piece of meat and subsequently used to section a prostatectomy specimen. Histology sections were compared with T2‐weighted MR images acquired in vivo before the prostatectomy procedure.

Results

The prostatectomy specimen slices were very uniform in thickness with each face parallel to the other with no visible sawing marks on the sections by the blades after the cut. MRI and histology comparison showed good correspondence between the two images.

Conclusion

The developed device allows sectioning of prostatectomy specimens into parallel cuts at a specific orientation and fixed intervals. Such a device is useful in facilitating accurate correlation between histology and MRI data. J. Magn. Reson. Imaging 2010;32:992–996. © 2010 Wiley‐Liss, Inc.
Neuropathological differences between rats and mice after spinal cord injury
Authors: Byrnes Kimberly R. , Fricke Stanley T. , Faden Alan I.
Published: September 2010

Purpose

To investigate the utility of noninvasive magnetic resonance imaging (MRI) protocols to demonstrate pathological differences between rats and mice after spinal cord injury (SCI). Rats and mice are commonly used to model SCI; however, histology and immunohistochemistry have shown differences in neuropathology between the two species, including cavity formation and scar/inflammatory responses.

Materials and Methods

Moderate contusion SCI was performed on adult male rats and mice. At 28 days postinjury, animals underwent T1‐weighted (T1W), with or without gadolinium contrast, or T2‐weighted (T2W) magnetic resonance imaging (MRI), to be compared with histology at the same timepoint.

Results

In both species, all MRI methods demonstrated changes in spinal cord anatomy. Immunohistochemistry indicated that T2W accurately reflected areas of inflammation and glial scar formation in rats and mice. Quantitation of lesion volume by histology and functional performance correlated best with T2W measurements in both species. Gadolinium contrast accurately reflected the blood‐spinal cord‐barrier permeability in both species, which appeared greater in rats than in mice.

Conclusion

These data demonstrate that MRI, with either a T1W or T2W protocol, can effectively distinguish pathological differences between rats and mice. J. Magn. Reson. Imaging 2010;32:836–846. © 2010 Wiley‐Liss, Inc.
Mechanical loading increased BMP‐2 expression which promoted osteogenic differentiation of tendon‐derived stem cells
Authors: Rui Yun Feng , Lui Pauline Po Yee , Ni Ming , Chan Lai Shan , Lee Yuk Wa , Chan Kai Ming
Published: September 2010

This study aimed to investigate the effect of repetitive tensile loading on the expression of BMP‐2 and the effect of BMP‐2 on the osteogenic differentiation of tendon‐derived stem cells (TDSCs) in vitro. Repetitive stretching was applied to TDSCs isolated from rat patellar tendon at 0%, 4%, and 8%, 0.5 Hz. The expression of BMP‐2 was detected by Western blotting and qPCR. To study the osteogenic effects of BMP‐2 on TDSCs, BMP‐2 was added to the TDSC monolayer for the detection of ALP activity and calcium nodule formation in a separate experiment. TDSCs adhered, proliferated, and aligned along the direction of externally applied tensile force while they were randomly oriented in the control group. Western blotting showed increased expression of BMP‐2 in 4% and 8% stretching groups but not in the control group. Up‐regulation of BMP‐2 mRNA was also observed in the 4% stretching group. BMP‐2 increased the osteogenic differentiation of TDSCs as indicated by higher ALP cytochemical staining, ALP activity, and calcium nodule formation. Repetitive tensile loading increased the expression of BMP‐2 and addition of BMP‐2 enhanced osteogenic differentiation of TDSCs. Activation of BMP‐2 expression in TDSCs during tendon overuse might provide a possible explanation of ectopic calcification in calcifying tendinopathy. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:390–396, 2011
Variations in varus/valgus and internal/external rotational knee laxity and stiffness across the menstrual cycle
Authors: Shultz Sandra J. , Schmitz Randy J. , Beynnon Bruce D.
Published: September 2010

Cyclic variations in genu recurvatum (GR), general joint laxity (GJL), varus–valgus (VV), and internal–external (IER) rotational laxities and stiffnesses were examined in 64 females and 43 males at two time points during the females' menstrual cycle [days of minimum (T1) and maximum (T2) anterior knee laxity (AKL)]. Cyclic increases in AKL (9.5%), GR (37.5%), and GJL (13.6%) were observed in females but not males from T1 to T2 (p < 0.001). Cyclic increases in VV and IER laxity were negligible (1.5–3.2%, p > 0.320). Females compared to males had lower overall VV stiffness at T2 (F 37% <M) vs. T1 (F 26.9% <M; p = 0.011), but no difference across time points for IER stiffness (p = 0.452). Across both time points, females had consistently greater VV (30.2%) and IER (20%) laxity and less VV (32.5%) and IER (24.3%) incremental stiffness (p < 0.001). Low‐to‐moderate associations were observed between AKL, GR, and GJL with VV and IER laxities and stiffnesses in females as measured at T1 and the change in values from T1 to T2. Whether these findings reflect ligament‐specific responses to hormone changes, or implicate changes in injury risk potential across the menstrual cycle requires further study. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:318–325, 2011
Tendon fascicle gliding in wild type, heterozygous, and lubricin knockout mice
Authors: Kohrs Ross T. , Zhao Chunfeng , Sun Yu‐Long , Jay Gregory D. , Zhang Ling , Warman Matthew L. , An Kai‐Nan , Amadio Peter C.
Published: September 2010

The objective of this study was to investigate the role of lubricin in the lubrication of tendon fascicles. Lubricin, a glycoprotein, lubricates cartilage and tendon surfaces, but the function of lubricin within the tendon fascicle is unclear. We developed a novel method to assess the gliding resistance of a single fascicle in a mouse tail model and used it to test the hypothesis that gliding resistance would be increased in lubricin knockout mice. Thirty‐six mouse tails were used from 12 wild type, 12 heterozygous, and 12 lubricin knockout mice. A 15 mm long fascicle segment was pulled proximally after being divided distally. The peak resistance during fascicle pullout and the fascicle perimeter were measured. Lubricin expression was evaluated by immunohistochemistry. The peak gliding resistance in the lubricin knockout mice was significantly higher than in the wild type (p < 0.05). Fascicles from heterozygous mice were intermediate in value, but not significantly different from either wild type or lubricin knockout fascicles in peak gliding resistance. No significant difference was found in fascicle perimeter among the three groups. No correlation was observed between fascicle perimeter and gliding resistance. While lubricin was detected by immunostaining on the fascicle surface in wild type and heterozygous mice, lubricin was not detectable in the tendons of knockout mice. We conclude that the absence of lubricin is associated with increased interfascicular friction and that lubricin may play an important role in interfascicular lubrication. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:384–389, 2011
The role of omental flap transposition in patients with locoregional recurrent rectal cancer treated with reirradiation
Authors: Kim Tae Hyun , Kim Dae Yong , Jung Kyung Hae , Hong Yong Sang , Kim Sun Young , Park Ji Won , Lim Seok‐Byung , Choi Hyo Seong , Jeong Seung‐Yong , Oh Jae Hwan
Published: September 2010

Background and Objectives

We performed reirradiation after omental flap transposition (OFT) in patients with locoregional recurrent rectal cancer (LRRC) and evaluated the effect of OFT on the irradiated small bowel by comparing the displacement of the small bowel from the radiation field before and after OFT.

Methods

Between October 2005 and October 2008, this study included 12 patients with LRRC who had previously received radiotherapy. To evaluate the effect of OFT on the irradiated volume of the small bowel and bladder, we measured the closest distances between the small bowel and the tumor or tumor bed (distanceSB) and between the bladder and tumor or tumor bed (distanceBL) before and after OFT, respectively.

Results

The median distanceSB before and after OFT was 5 and 30 mm, respectively (P < 0.001). The median distanceBL before and after OFT was 10 and 23 mm, respectively (P = 0.002). The respective overall survival and local control rates at 3 years were 50.9% and 54.6%, respectively. No severe complication occurred of grade 3 or higher involving the small bowel or bladder.

Conclusions

In our study, OFT effectively excluded small bowel from the radiation field. In addition, selective reirradiation after OFT was feasible for patients with LRRC. J. Surg. Oncol. 2010;102:789–795. © 2010 Wiley‐Liss, Inc.
Evaluation of environmental contamination by platinum and exposure risks for healthcare workers during a heated intraperitoneal perioperative chemotherapy (HIPEC) procedure
Authors: Konate Armande , Poupon Joël , Villa Antoine , Garnier Robert , Hasni‐Pichard Hélène , Mezzaroba Danielle , Fernandez Gabriel , Pocard Marc
Published: September 2010

The study was plan to assess platinum (Pt) contamination in the operating room and its exposure to health workers during heated intraperitoneal perioperative chemotherapy (HIPEC) using oxaliplatin.

Materials and Methods

Pt was measured in urinary and environmental (air and surfaces) samples via inductively coupled plasma mass spectrometry (ICP‐MS). Urinary samples were obtained from 11 members of the staff before and after the procedure and from 6 controls. Samples from 15 surfaces and from 3 filters from the air extractors were also analyzed for Pt contamination.

Results

Before HIPEC, Pt levels in urinary samples were similar in both the exposed and control groups; concentrations were below the limit of detection (i.e., 1.5 ng/L). No elevation was observed in the exposed group at the end of the procedure. Surgeon gloves were heavily contaminated. On other analyzed surfaces, lesser amounts of Pt were measured, ranging from 2 ng on the surgeon's hands to 183 ng on the forceps. All three air filters tested negative.

Conclusion

No contamination of healthcare workers or of the air in the operating room was detected. However, the heavy contamination of the surgeon's gloves demonstrates why doubling of specialized gloves for the surgeon should be mandatory. J. Surg. Oncol. 2011;103:6–9. © 2010 Wiley‐Liss, Inc.
Interferon‐α therapy after curative resection prevents early recurrence and improves survival in patients with hepatitis B virus‐related hepatocellular carcinoma
Authors: Qu Li‐Shuai , Jin Fei , Huang Xiao‐Wu , Shen Xi‐Zhong
Published: September 2010

Background

A retrospective cohort study was conducted to investigate the effect of interferon‐α (IFN‐α) therapy after curative resection on survival and recurrence in patients with hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC).

Methods

Of 568 HBV‐related HCC patients who underwent curative resection, 101 patients received postoperative IFN‐α therapy (5 million units three times every week for 18 months). Clinicopathological factors were compared between patients with postoperative IFN‐α therapy or not. Risk factors for survival, early, and late recurrence (2 years as cut‐off) were studied.

Results

The median follow‐up time was 53.3 months. There was no significant difference in clinicopathological factors between the two groups. Patients with postoperative IFN‐α therapy had higher overall survival rates (hazards ratio (HR): 0.612, 95% confidence interval (CI): 0.422–0.889, P = 0.010). No significant difference in disease‐free survival rates was detected between the two groups (HR: 0.786, 95% CI: 0.597–1.035, P = 0.086). Multivariate analysis revealed that postoperative IFN‐α therapy was an independent factor for overall survival (HR: 0.611, 95% CI: 0.421–0.887, P = 0.010) and significantly reduced early recurrence (HR: 0.562, 95% CI: 0.375–0.840, P = 0.005).

Conclusions

IFN‐α therapy after curative resection prevented early recurrence and improved overall survival of patients with HBV‐related HCC. J. Surg. Oncol. 2010;102:796–801. © 2010 Wiley‐Liss, Inc.
The association of frequent allelic loss on 17p13.1 with early metastastic recurrence of hepatocellular carcinoma after liver transplantation
Authors: Zhou Lin , Zhou Wuhua , Wu Liming , Yu Xiaobo , Xing Chunyang , Zheng Shusen
Published: September 2010

Background and Objectives

Identification and characterization of loss of heterozygosity (LOH) can determine putative tumor suppressor genes (TSGs) and provide a variety of molecular markers for hepatocellular carcinoma (HCC). This study aimed to investigate LOH status on chromosomes 4q, 6q, 8p, 9p, and 17p, and to explore their clinical significances in HCC post‐liver transplantation.

Methods

A total of 37 patients with HCC who underwent liver transplantation were enrolled. LOH was examined using 34 microsatellite markers located on 4q13‐3q5, 6q27, 8p22‐p23, 9p21‐p22, and 17p12‐p13.

Results

The frequency of LOH at each microsatellite locus ranged from 23% to 75%, with a mean value of 53.1%. Frequencies of LOH on 4q, 6q, 8p, 9p, and 17p were 62% (23 of 37), 30% (11 of 37), 49% (18 of 37), 46% (16 of 35), and 68% (25 of 37), respectively. LOHs on certain chromosomal regions were significantly associated with age, AFP level, tumor size, tumor multiplicity, histological grade, and metastatic recurrence.

Conclusions

LOH on 17p13.1 correlated to metastatic HCC recurrence, while LOH on 4q and 8p was found to be associated with progression of HCC. Thus, potential novel biomarkers or TSGs for prognosis and treatment of HCC may harbor on these regions. J. Surg. Oncol. 2010;102:802–808. © 2010 Wiley‐Liss, Inc.
Differential effect of hyperthermia on nerves and smooth muscle of the mouse ileum
Authors: Burke Shoshana , Abu‐Wasel Basam , Eid Ahmed , Nissan Aviram , Hanani Menachem
Published: September 2010

Background and Objectives

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) gained wide acceptance as the treatment of choice for selected patients with peritoneal surface malignancies. Patients tend to suffer from prolonged ileus following CRS + HIPEC, complicating their recovery. We studied the effects of hyperthermia on the intestine to gain insight into mechanisms of ileus post‐HIPEC.

Methods

Segments of mouse ileum were incubated at 36°C. Electrical field stimulation (EFS) was applied, stimulating nerves, and the resultant muscle contraction was measured. The response was measured at varying temperatures (38–43°C) at exposure times of up to 120 min. We also stimulated the tissues with 10−6 M carbachol, a muscarinic receptor agonist, which acts directly on smooth muscle.

Results

Response to EFS decreased at high temperatures, especially above 41°C. This effect was irreversible for 120 min after decreasing temperature. When stimulating with carbachol, both transient and plateau responses decreased at 43°C (plateau more than transient) but the effect reversed on returning to 36°C.

Conclusion

The irreversible decline in responses to nerve stimulation when exposed to high temperatures was not seen with direct muscle stimulation. This indicates that smooth muscle is resilient and that the main effect of hyperthermia is on nerves. These results have significance for HIPEC. J. Surg. Oncol. 2011;103:92–100. © 2010 Wiley‐Liss, Inc.
Rapid separation and immunoassay for low levels of Salmonella in foods using magnetosome–antibody complex and real‐time fluorescence quantitative PCR
Authors: Li Aihua , Zhang Huiyuan , Zhang Xin , Wang Qi , Tian Jiesheng , Li Ying , Li Jilun
Published: September 2010

A rapid and economical method for detecting Salmonella was developed, based on a novel complex for immunomagnetic separation, which was composed of anti‐Salmonella polyclonal antibody (Ab) and magnetosome (bacterial magnetic particle, BMP) produced by the bacterium Magnetospirillum gryphiswaldense MSR‐1. BMP‐Ab complex was used to capture Salmonella from pure suspensions of S. dublin, S. enteritidis, S. aesch, S. agona, S. abony and S. bareily, from mixed suspensions of S. dublin and Vibrio parahaemolyticus, and from artificially contaminated food samples. Captured Salmonella were then detected by plate count, or real‐time fluorescence quantitative PCR. Capture efficiencies, calculated from plate count, were >80% for the pure Salmonella suspensions of all six strains, and >70% for the mixed suspension. Samples of six food products, with artificial contamination by 6000, 600, 60, or 0.6 cfu/mL S. dublin, were captured by complex and detected by real‐time fluorescence quantitative PCR. Threshold cycle values varied depending on type of food. The lower limit of detectability was 60 cfu/mL without pre‐enrichment, and <0.6 cfu/mL after 3‐h pre‐enrichment. The method described here, based on capture pathogens by BMP‐Ab complex, is sensitive, rapid, and considerably simpler than traditional methods for Salmonella detection. It can be extended to other pathogens by the use of appropriate antibodies.
Multiple trauma and mental health in former Ugandan child soldiers
Authors: Klasen Fionna , Oettingen Gabriele , Daniels Judith , Adam Hubertus
Published: September 2010

The present study examines the effect of war and domestic violence on the mental health of child soldiers in a sample consisting of 330 former Ugandan child soldiers (age: 11–17 years, female: 49%). All children had experienced at least 1 war‐related event and 78% were additionally exposed to at least 1 incident of domestic violence. Prevalences of posttraumatic stress disorder and major depressive disorder were 33%, and 36%, respectively. Behavioral and emotional problems above clinical cutoff were measured in 61%. No gender differences were found regarding mental health outcomes. War experience and domestic violence were significantly associated with all mental health outcomes. The authors' findings point to the detrimental effects of domestic violence in addition to traumatizing war experiences in child soldiers.
Synthesis, Characterization and Field‐Effect Transistor Performance of Poly[2,6‐bis(3‐alkylthiophen‐2‐yl)benzo[1,2‐b;4,5‐b′]diselenophene]s
Authors: Leenen Mark A.M. , Vian Fiona , Cucinotta Fabio , Pisula Wojciech , Thiem Heiko , Anselmann Ralf , De Cola Luisa
Published: September 2010

Benzo[1,2‐b:4,5‐b′]diselenophene (BDS) has been incorporated for the first time in a polymer. bis(Stannyl)‐functionalized BDS was copolymerized with 3,3′‐bis(alkyl)‐5,5′‐bithiophenes (dodecyl and tetradecyl side chains) through Stille copolymerization, to yield p‐type polymer semiconductors for organic field‐effect transistor application. The electronic and structural effect of the selenium atoms, compared to sulphur atoms in analogous copolymers, is described. The molecular weight has a decisive influence on the photophysical properties and supramolecular ordering, expressed in field‐effect transistor measurements. Saturation mobilities around 10−2 cm2 · V−1s−1 are obtained on standard silicon substrates.

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Disulfide‐Crosslinked Biomimetic Micelles: Formation, Thiol Reactivity and Cytotoxicity Behavior
Authors: Lv Li‐Ping , Xu Jian‐Ping , Liu Xiang‐Sheng , Liu Gong‐Yan , Yang Xuan , Ji Jian
Published: September 2010

A series of amphiphilic random copolymers with MPC as the hydrophilic segment, SMA as the hydrophobic segment and GMA as the reactive segment were synthesized. Polymeric micelles with different sizes were obtained through tuning the hydrophilic/hydrophobic segment ratios in the copolymers. The formation and properties of these micelles were investigated using 1H NMR spectroscopy, fluorescence probe techniques and DLS. The reactive polymeric micelles were crosslinked with a di‐functional reagent. The crosslinked micelles showed improved stability and thiol reactivity. Cell viability tests indicated that the bioinspired phosphorylcholine‐based micelles showed excellent biocompatibility, thus promising great potential for applications in the field of nanocarrier systems.

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A New Halogen‐Free Flame Retardant Based on 9,10‐Dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide for Epoxy Resins and their Carbon Fiber Composites for the Automotive and Aviation Industries
Authors: Perret Birgit , Schartel Bernhard , Stöß Kai , Ciesielski Michael , Diederichs Jan , Döring Manfred , Krämer Johannes , Altstädt Volker
Published: September 2010

The pyrolysis and fire behavior of halogen‐free flame‐retarded DGEBA/DMC, RTM6 and their corresponding 60 vol.‐% carbon fibers (CF) composites were investigated. A novel phosphorous compound (DOPI) was used. Its action is dependent on the epoxy matrix. DGEBA/DMC and DOPI decompose independently of each other. Only flame inhibition occurs in the gas phase. RTM6 shows flame inhibition and a condensed phase interaction increasing charring. Both mechanisms decrease with increasing irradiance, whereas in RTM6‐CF charring is suppressed at low ones. RTM6 + DOPI shows a higher LOI (34.2%) than DGEBA/DMC + DOPI and a V‐0 classification in UL 94. Adding CF only enhances the LOI, DOPI + CF leads to a superposition in LOI for DGEBA/DMC‐CF + DOPI (31.8%, V‐0) and a synergism for RTM6‐CF + DOPI (47.7%, V‐0).

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Graphene Nanocomposites Prepared From Blends of Polymer Latex with Chemically Reduced Graphite Oxide Dispersions
Authors: Wissert Rainer , Steurer Peter , Schopp Stephanie , Thomann Ralf , Mülhaupt Rolf
Published: September 2010

Graphene nanocomposites are prepared by chemical reduction of graphite oxide (GO) dispersion with vitamin C in the presence of SAN latex followed by melt compounding. In this process, GO is well dispersed in an aqueous SAN emulsion before reduction. During reduction the SAN latex is adsorbed on the graphene sheets of the chemically reduced GO (CRGO). After melt compounding of such hybrid particles with SAN, the nanocomposites show uniform dispersion of CRGO in SAN resulting in improved stiffness with respect to SAN/graphite. The reduction of GO in the presence of polymer latex represents a versatile route to graphene masterbatches and does not require either drying of GO or thermal GO expansion at high temperatures.

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Dynamic in vivo changes in the activities of gelatinases, matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases (TIMPs) in buffalo (Bubalus bubalis) uterine luminal fluid during estrous cycle and early pregnancy
Authors: Roy Sudhir C. , Ghosh Jyotirmoy
Published: September 2010

In ruminants, the phenomenon of endometrial tissue remodeling during the estrous cycle and early pregnancy is not fully understood. In this report, the occurrence of tissue remodeling, if any, in buffalo endometrium was studied by detecting gelatinases, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs); the key regulators of tissue remodeling, in uterine luminal fluids (ULF) of cycling and early pregnant (approx. 43–65 days) buffaloes. Each stage of the estrous cycle and pregnant ULF demonstrated a unique profile of gelatinase activities compared to serum/follicular fluid, with a major gelatinase band of 60 kDa with highest activity in early‐luteal stage. In addition to a 32 kDa uterus‐specific gelatinase band detected in both non‐pregnant and pregnant ULFs, the pregnant ULF displayed three new gelatinase bands of 86, 78, and 57 kDa. Western blot technique confirmed the presence of MMP‐2 (54 kDa), MMP‐9 (76/73 kDa), TIMP‐1 (32 kDa), TIMP‐2(20 kDa), and two molecular weight forms (31 and 22 kDa) of TIMP‐3 in buffalo ULF with varying band intensities. Highest MMP‐2 and MMP‐9 activities were observed in follicular and early‐luteal stage ULFs, respectively. Highest TIMP‐1 activity was observed in early‐luteal ULF. Interestingly, TIMP‐2 activity was only detected in mid‐luteal, late‐luteal, and follicular stage ULFs with significantly increasing intensities. Highest activities of 31 and 22 kDa TIMP‐3 were associated with late‐luteal and early‐luteal stage ULFs, respectively. The varied activities of MMPs and TIMPs in buffalo ULF during the estrous cycle and early pregnancy might be a reflection of dynamic structural remodeling of the endometrium and/or developing conceptus. Mol. Reprod. Dev. 77:944–953, 2010. © 2010 Wiley‐Liss, Inc.
Rapid three‐dimensional multicomponent relaxation imaging of the cervical spinal cord
Authors: Kolind Shannon H. , Deoni Sean C.
Published: September 2010

Currently, little is known about the pathology of myelin in spinal cord disease due to the technical challenges of specifically measuring myelin content noninvasively. Multicomponent relaxometry allows estimation of the myelin water fraction, which is related to myelin content. However, conventional multiple‐echo spin–echo‐based multicomponent relaxometry techniques require prohibitively long acquisition times, lack spatial coverage, and are sensitive to artifacts common in spinal cord imaging. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) offers a promising alternative to conventional multicomponent relaxometry techniques. The goal of this pilot study was to assess the efficacy of mcDESPOT for obtaining high spatial resolution spinal cord myelin water fraction data covering the entire cervical spinal cord. Myelin water fraction values were found to be highly reproducible between subjects and over time but varied considerably along the length of the cord. Other relaxation characteristics that relate to tissue structure and health were also reliably measured. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.
A randomized trial of coenzyme Q10 in mitochondrial disorders
Authors: Glover Elisa I. , Martin Joan , Maher Amy , Thornhill Rebecca E. , Moran Gerald R. , Tarnopolsky Mark A.
Published: September 2010

Case reports and open‐label studies suggest that coenzyme Q10 (CoQ10) treatment may have beneficial effects in mitochondrial disease patients; however, controlled trials are warranted to clinically prove its effectiveness. Thirty patients with mitochondrial cytopathy received 1200 mg/day CoQ10 for 60 days in a randomized, double‐blind, cross‐over trial. Blood lactate, urinary markers of oxidative stress, body composition, activities of daily living, quality of life, forearm handgrip strength and oxygen desaturation, cycle exercise cardiorespiratory variables, and brain metabolites were measured. CoQ10 treatment attenuated the rise in lactate after cycle ergometry, increased (∽1.93 ml) VO2/kg lean mass after 5 minutes of cycling (P < 0.005), and decreased gray matter choline‐containing compounds (P < 0.05). Sixty days of moderate‐ to high‐dose CoQ10 treatment had minor effects on cycle exercise aerobic capacity and post‐exercise lactate but did not affect other clinically relevant variables such as strength or resting lactate. Muscle Nerve, 2010
Properties of extensor digitorum longus muscle and skinned fibers from adult and aged male and female Actn3 knockout mice
Authors: Chan Stephen , Seto Jane T. , Houweling Peter J. , Yang Nan , North Kathryn N. , Head Stewart I.
Published: September 2010

Absence of α‐actinin‐3, encoded by the ACTN3 “speed gene,” is associated with poorer sprinting performance in athletes and a slowing of relaxation in fast‐twitch muscles of Actn3 knockout (KO) mice. Our first aim was to investigate, at the individual‐fiber level, possible mechanisms for this slowed relaxation. Our second aim was to characterize the contractile properties of whole extensor digitorum longus (EDL) muscles from KO mice by age and gender. We examined caffeine‐induced Ca2+ release in mechanically skinned EDL fibers from KO mice, and measured isolated whole EDL contractile properties. The sarcoplasmic reticulum of KO muscle fibers loaded Ca2+ more slowly than that of wild‐types (WTs). Whole KO EDL muscles had longer twitch and tetanus relaxation times than WTs, and reduced mass and cross‐sectional area. These effects occurred in both male and female mice, but they diminished with age. These changes in KO muscles and fibers help to explain the effects of α‐actinin‐3 deficiency observed in athletes. Muscle Nerve, 2011
Muscle ultrasound quantifies the rate of reduction of muscle thickness in amyotrophic lateral sclerosis
Authors: Lee Christopher D. , Song Yanna , Peltier Amanda C. , Jarquin‐Valdivia Adrian A. , Donofrio Peter D.
Published: September 2010

Sensitive biomarkers are lacking in amyotrophic lateral sclerosis (ALS). Muscle ultrasound (MUS) can quantify muscle thickness and echointensity (EI). We evaluated the rate of muscle atrophy in ALS using MUS. Ten patients had serial unilateral MUS examination of biceps, wrist flexors, and tibialis anterior over 6 months. The rates of change of muscle thickness and EI were determined. Muscle thickness declined at a mean rate of −0.663 mm/month (P = 0.0014), greatest in biceps. Muscle thickness correlated moderately with ALSFRS‐R, grip dynamometry, and body weight. There was no change in EI. MUS can quantify the rate of reduction in muscle thickness in ALS patients. The lack of strong correlation between muscle thickness and standard ALS measures may reflect limited sensitivity in these conventional measures. The rate of change of muscle thickness merits further study as a potential biomarker in ALS, particularly when considering biceps brachii as a candidate. Muscle Nerve, 2010
Monte Carlo study of a two‐compartment exchange model of diffusion
Authors: Fieremans Els , Novikov Dmitry S. , Jensen Jens H. , Helpern Joseph A.
Published: September 2010

Multisite exchange models have been applied frequently to quantify measurements of transverse relaxation and diffusion in living tissues. Although the simplicity of such models is attractive, the precise relationship of the model parameters to tissue properties may be difficult to ascertain. Here, we investigate numerically a two‐compartment exchange (Kärger) model as applied to diffusion in a system of randomly packed identical parallel cylinders with permeable walls, representing cells with permeable membranes, that may serve particularly as a model for axons in the white matter of the brain. By performing Monte Carlo simulations of restricted diffusion, we show that the Kärger model may provide a reasonable coarse‐grained description of the diffusion‐weighted signal in the long time limit, as long as the cell membranes are sufficiently impermeable, i.e. whenever the residence time in a cell is much longer than the time it takes to diffuse across it. For larger permeabilities, the exchange time obtained from fitting to the Kärger model overestimates the actual exchange time, leading to an underestimated value of cell membrane permeability. Copyright © 2010 John Wiley & Sons, Ltd.
A system and mathematical framework to model shear flow effects in biomedical DW‐imaging and spectroscopy
Authors: Nevo Uri , Özarslan Evren , Komlosh Michal E. , Koay Cheng Guan , Sarlls Joelle E. , Basser Peter J.
Published: September 2010

The pulsed‐field gradient (PFG) MR experiment enables one to measure particle displacements, velocities, and even higher moments of complex fluid motions. In diffusion‐weighted MRI (DWI) in living tissue, where the PFG MRI experiment is used to measure diffusion, Brownian motion is assumed to dominate the displacements causing the observed signal loss. However, motions of water molecules caused by various active biological processes occurring at different length and time scales may also cause additional dephasing of magnetization and signal loss. To help understand their relative effects on the DWI signal attenuation, we used an integrated experimental and theoretical framework: a Rheo‐NMR, which served as an experimental model system to precisely prescribe a microscopic velocity distribution; and a mathematical model that relates the DW signal intensity in the Rheo‐NMR to experimental parameters that characterize the impressed velocity field. A technical innovation reported here is our use of ‘natural’ (in this case, polar) coordinates both to simplify the description the fluid motion within the Couette cell of the Rheo‐NMR, as well as to acquire and reconstruct magnitude and phase MR images obtained within it. We use this integrated model system to demonstrate how shear flows appears as pseudo‐diffusion in magnitude DW MR signals obtained using PFG spin‐echo (PGSE) NMR and MRI sequences. Our results lead us to reinterpret the possible causes of signal loss in DWI in vivo, in particular to revise and generalize the previous notion of intra‐voxel incoherent motion (IVIM) in order to describe activity driven flows that appear as pseudo‐diffusion over multiple length and time scales in living tissues. Copyright © 2010 John Wiley & Sons, Ltd.