bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychotherapeutic and Pharmacologic Treatment of Schizotypal Personality Disorder
Authors: Nathanson Bruce J. , Jamison Suzanna Connick
Published: November 2011

Although the traditional emphasis on overt symptomatology leads readily to diagnosis, such categorization typically assumes a pathological process within the individual that may at best be managed or modified. Conceptualization of symptoms in terms of adaptive and functional considerations may facilitate and broaden options for treatment, potentially improving outcome. This case study provides an example of treatment of schizotypal personality disorder using such an approach. Psychotherapy and medication were directed toward alleviating symptoms of anxiety and depression producing functional impairment in memory, and development of interpersonal skills to increase prospects for reinforcement in interaction with others was implemented to decrease the need for fantasy as a means of obtaining such gratification. Psychotherapy focused on selectively reinforcing positive self-statements, social skills training, and anxiety reduction. Serendipitous peer modeling also facilitated therapeutic efforts. The anxiolytic buspirone, the serotonin-selective reuptake inhibitor citalopram, and the stimulants dextroamphetamine and amphetamine, and methylphenidate were effective in pharmacologic management. This treatment approach was found to be beneficial not only in terms of self-report and peer appraisal but also in results of psychological assessment, including a neuropsychological screening measure.
Plug-in estimation of d-dimensional density minimum volume set of a rare event in a complex system
Authors: Morio J , Pastel R
Published: November 2011

Various reliability or hedging problems boil down to quantile estimation. However, real-life systems are usually multidimensional and thus often imply multidimensional density minimum volume set estimation which is usually done with Monte Carlo simulations. Increasing safety standards create a need for density minimum volume set estimation with low probability that crude Monte Carlo cannot fulfil. This paper proposes a new importance sampling algorithm that estimates efficiently multidimensional density minimum volume sets for extreme probability. It also presents some numerical results on a simple bidimensional Gaussian case and on a realistic launcher impact safety zone estimation.
Risks and benefits with bevacizumab: evidence and clinical implications
Authors: Kurkjian Carla , Kim Edward S.
Published: November 2011

With the 1997 filing of an investigational new drug application for the first agent to target angiogenesis, bevacizumab entered into phase I clinical trials and has now become a mainstay in the treatment of several cancers. Bevacizumab has changed the treatment approach for cancers due to its efficacy as well as toxicity. This article serves as a review of current efficacy data including recently published safety analyses and the direction of future pharmacodynamic evaluation to hopefully better guide its utilization.
A novel pathway for human endothelial cell activation by antiphospholipid/anti-β2 glycoprotein I antibodies
Authors: Allen Kristi L. , Fonseca Fabio V. , Betapudi Venkaiah , Willard Belinda , Zhang Jainwei , McCrae Keith R.
Published: November 2011

Antiphospholipid Abs (APLAs) are associated with thrombosis and recurrent fetal loss. These Abs are primarily directed against phospholipid-binding proteins, particularly β2GPI, and activate endothelial cells (ECs) in a β2GPI-dependent manner after binding of β2GPI to EC annexin A2. Because annexin A2 is not a transmembrane protein, the mechanisms of APLA/anti-β2GPI Ab–mediated EC activation are uncertain, although a role for a TLR4/myeloid differentiation factor 88–dependent pathway leading to activation of NF-κB has been proposed. In the present study, we confirm a critical role for TLR4 in anti-β2GPI Ab–mediated EC activation and demonstrate that signaling through TLR4 is mediated through the assembly of a multiprotein signaling complex on the EC surface that includes annexin A2, TLR4, calreticulin, and nucleolin. An essential role for each of these proteins in cell activation is suggested by the fact that inhibiting the expression of each using specific siRNAs blocked EC activation mediated by APLAs/anti-β2GPI Abs. These results provide new evidence for novel protein-protein interactions on ECs that may contribute to EC activation and the pathogenesis of APLA/anti-β2GPI–associated thrombosis and suggest potential new targets for therapeutic intervention in antiphospholipid syndrome.
Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients
Authors: Schönland Stefan O. , Hegenbart Ute , Bochtler Tilmann , Mangatter Anja , Hansberg Marion , Ho Anthony D. , Lohse Peter , Röcken Christoph
Published: November 2011

Amyloidoses are characterized by organ deposition of misfolded proteins. This study evaluated immunohistochemistry as a diagnostic tool for the differentiation of amyloid subentities, which is warranted for accurate treatment. A total of 117 patients were systematically investigated by clinical examination, laboratory tests, genotyping, and immunohistochemistry on biopsy specimens. Immunohistochemistry enabled the classification in 94% of the cases. For subsequent analysis, the patient population was divided into 2 groups. The first group included all patients whose diagnosis could be verified by typical clinical signs or an inherited amyloidogenic mutation. In this group, immunohistochemical subtyping was successful in 49 of 51 cases and proved accurate in each of the 49 cases, corresponding to a sensitivity of 96% and a specificity of 100%. The second group included patients with systemic light chain amyloidosis without typical signs, senile transthyretin, or hereditary amyloidosis with a concomitant monoclonal gammopathy. Immunohistochemistry allowed to define the subentities in 61 of 66 (92%) of these cases. Immunohistochemistry performed by a highly specialized pathologist combined with clinical examination and genotyping leads to a high accuracy of amyloidosis classification and is the standard in our center. However, new techniques, such as mass spectroscopy-based proteomics, were recently developed to classify inconclusive cases.
The Sumo-targeted ubiquitin ligase RNF4 regulates the localization and function of the HTLV-1 oncoprotein Tax
Authors: Fryrear Kimberly A. , Guo Xin , Kerscher Oliver , Semmes O. John
Published: November 2011

The Really Interesting New Gene (RING) Finger Protein 4 (RNF4) represents a class of ubiquitin ligases that target Small Ubiquitin-like Modifier (SUMO)–modified proteins for ubiquitin modification. To date, the regulatory function of RNF4 appears to be ubiquitin-mediated degradation of sumoylated cellular proteins. In the present study, we show that the Human T-cell Leukemia Virus Type 1 (HTLV-1) oncoprotein Tax is a substrate for RNF4 both in vivo and in vitro. We mapped the RNF4-binding site to a region adjacent to the Tax ubiquitin/SUMO modification sites K280/K284. Interestingly, RNF4 modification of Tax protein results in relocalization of the oncoprotein from the nucleus to the cytoplasm. Overexpression of RNF4, but not the RNF4 RING mutant, resulted in cytoplasmic enrichment of Tax. The RNF4-induced nucleus-to-cytoplasm relocalization was associated with increased NF-κB–mediated and decreased cAMP Response Element-Binding (CREB)–mediated Tax activity. Finally, depletion of RNF4 by RNAi prevented the DNA damage–induced nuclear/cytoplasmic translocation of Tax. These results provide important new insight into STUbL-mediated pathways that regulate the subcellular localization and functional dynamics of viral oncogenes.
Role and regulation of phosphatidylinositol 3-kinase β in platelet integrin α2β1 signaling
Authors: Consonni Alessandra , Cipolla Lina , Guidetti Gianni , Canobbio Ilaria , Ciraolo Elisa , Hirsch Emilio , Falasca Marco , Okigaki Mitsuhiko , Balduini Cesare , Torti Mauro
Published: November 2011

Integrin α2β1–mediated adhesion of human platelets to monomeric type I collagen or to the GFOGER peptide caused a time-dependent activation of PI3K and Akt phosphorylation. This process was abrogated by pharmacologic inhibition of PI3Kβ, but not of PI3Kγ or PI3Kα. Moreover, Akt phosphorylation was undetectable in murine platelets expressing a kinase-dead mutant of PI3Kβ (PI3KβKD), but occurred normally in PI3KγKD platelets. Integrin α2β1 failed to stimulate PI3Kβ in platelets from phospholipase Cγ2 (PLCγ2)–knockout mice, and we found that intracellular Ca2+ linked PLCγ2 to PI3Kβ activation. Integrin α2β1 also caused a time-dependent stimulation of the focal kinase Pyk2 downstream of PLCγ2 and intracellular Ca2+. Whereas activation of Pyk2 occurred normally in PI3KβKD platelets, stimulation of PI3Kβ was strongly reduced in Pyk2-knockout mice. Neither Pyk2 nor PI3Kβ was required for α2β1–mediated adhesion and spreading. However, activation of Rap1b and inside-out stimulation of integrin αIIbβ3 were reduced after inhibition of PI3Kβ and were significantly impaired in Pyk2-deficient platelets. Finally, both PI3Kβ and Pyk2 significantly contributed to thrombus formation under flow. These results demonstrate that Pyk2 regulates PI3Kβ downstream of integrin α2β1, and document a novel role for Pyk2 and PI3Kβ in integrin α2β1 promoted inside-out activation of integrin αIIbβ3 and thrombus formation.
MLVA genotyping of Chinese human Brucella melitensisbiovar 1, 2 and 3 isolates
Authors: Jiang Hai , Fan Mengguang , Chen Jingdiao , Mi Jingchuan , Yu Ruiping , Zhao Hongyan , Piao Dongri , Ke Changwen , Deng Xiaoling , Tian Guozhong , Cui Buyun
Published: November 2011

Background

Since 1950, Brucella melitensis has been the predominant strain associated with human brucellosis in China. In this study we investigated the genotypic characteristics of B. melitensis isolates from China using a multiple-locus variable-number tandem-repeat analysis (MLVA) and evaluated the utility of MLVA with regards to epidemiological trace-back investigation.

Results

A total of 105 B. melitensis strains isolated from throughout China were divided into 69 MLVA types using MLVA-16. Nei's genetic diversity indices for the various loci ranged between 0.00 - 0.84. 12 out 16 loci were the low diversity with values < 0.2 and the most discriminatory markers were bruce16 and bruce30 with a diversity index of > 0.75 and containing 8 and 7 alleles, respectively. Many isolates were single-locus or double-locus variants of closely related B. melitensis isolates from different regions, including the north and south of China. Using panel 1, the majority of strains (84/105) were genotype 42 clustering to the 'East Mediterranean' B. melitensis group. Chinese B. melitensis are classified in limited number of closely related genotypes showing variation mainly at the panel 2B loci.

Conclusion

The MLVA-16 assay can be useful to reveal the predominant genotypes and strain relatedness in endemic or non-endemic regions of brucellosis. However it is not suitable for biovar differentiation of B. melitensis. Genotype 42 is widely distributed throughout China during a long time. Bruce 16 and bruce 30 in panel 2B markers are most useful for typing Chinese isolates.
SWI/SNF regulates the alternative processing of a specific subset of pre-mRNAs in Drosophila melanogaster
Authors: Waldholm Johan , Wang Zhi , Brodin David , Tyagi Anu , Yu Simei , Theopold Ulrich , Farrants Ann Kristin Östlund , Visa Neus
Published: November 2011

Background

The SWI/SNF chromatin remodeling factors have the ability to remodel nucleosomes and play essential roles in key developmental processes. SWI/SNF complexes contain one subunit with ATPase activity, which in Drosophila melanogaster is called Brahma (Brm). The regulatory activities of SWI/SNF have been attributed to its influence on chromatin structure and transcription regulation, but recent observations have revealed that the levels of Brm affect the relative abundances of transcripts that are formed by alternative splicing and/or polyadenylation of the same pre-mRNA.

Results

We have investigated whether the function of Brm in pre-mRNA processing in Drosophila melanogaster is mediated by Brm alone or by the SWI/SNF complex. We have analyzed the effects of depleting individual SWI/SNF subunits on pre-mRNA processing throughout the genome, and we have identified a subset of transcripts that are affected by depletion of the SWI/SNF core subunits Brm, Snr1 or Mor. The fact that depletion of different subunits targets a subset of common transcripts suggests that the SWI/SNF complex is responsible for the effects observed on pre-mRNA processing when knocking down Brm. We have also depleted Brm in larvae and we have shown that the levels of SWI/SNF affect the pre-mRNA processing outcome in vivo.

Conclusions

We have shown that SWI/SNF can modulate alternative pre-mRNA processing, not only in cultured cells but also in vivo. The effect is restricted to and specific for a subset of transcripts. Our results provide novel insights into the mechanisms by which SWI/SNF regulates transcript diversity and proteomic diversity in higher eukaryotes.
Retrospective study of necrotizing fasciitis and characterization of its associated Methicillin-resistant Staphylococcus aureusin Taiwan
Authors: Changchien Chih-Hsuan , Chen Ying-Ying , Chen Shu-Wun , Chen Wan-Lin , Tsay Jwu-Guh , Chu Chishih
Published: November 2011

Background

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a prevalent pathogen of necrotizing fasciitis (NF) in Taiwan. A four-year NF cases and clinical and genetic differences between hospital acquired (HA)- and community-acquired (CA)-MRSA infection and isolates were investigated.

Methods

A retrospective study of 247 NF cases in 2004-2008 and antimicrobial susceptibilities, staphylococcal chromosomal cassette mec (SCCmec) types, pulsed field gel electrophoresis (PFGE) patterns, virulence factors, and multilocus sequence typing (MLST) of 16 NF-associated MRSA in 2008 were also evaluated.

Results

In 247 cases, 42 microbial species were identified. S. aureus was the major prevalent pathogen and MRSA accounted for 19.8% of NF cases. Most patients had many coexisting medical conditions, including diabetes mellitus, followed by hypertension, chronic azotemia and chronic hepatic disease in order of decreasing prevalence. Patients with MRSA infection tended to have more severe clinical outcomes in terms of amputation rate (p < 0.05) and reconstruction rate (p = 0.001) than those with methicillin-sensitive S. aureus or non-S. aureus infection. NF patients infected by HA-MRSA had a significantly higher amputation rate, comorbidity, C-reactive protein level, and involvement of lower extremity than those infected by CA-MRSA. In addition to over 90% of MRSA resistant to erythromycin and clindamycin, HA-MRSA was more resistant than CA-MRSA to trimethoprim-sulfamethoxazole (45.8% vs. 4%). ST59/pulsotype C/SCCmec IV and ST239/pulsotype A/SCCmec III isolates were the most prevalent CA- and HA-MRSA, respectively in 16 isolates obtained in 2008. In contrast to the gene for γ-hemolysin found in all MRSA, the gene for Panton-Valentine leukocidin was only identified in ST59 MRSA isolates. Other three virulence factors TSST-1, ETA, and ETB were occasionally identified in MRSA isolates tested.

Conclusion

NF patients with MRSA infection, especially HA-MRSA infection, had more severe clinical outcomes than those infected by other microbial. The prevalent NF-associated MRSA clones in Taiwan differed distinctly from the most predominant NF-associated USA300 CA-MRSA clone in the USA. Initial empiric antimicrobials with a broad coverage for MRSA should be considered in the treatment of NF patients in an endemic area.
Accuracy of physical activity assessment during pregnancy: an observational study
Authors: Smith Katie M , Foster Randal C , Campbell Christina G
Published: November 2011

Background

Prenatal physical activity may improve maternal and infant health and lower future disease risk for both mother and baby; however, very few physical activity assessment methods have been validated for use during pregnancy. The purpose of this study was to evaluate the accuracy of a subjective physical activity record (PAR) and an objective activity monitor, against a reference standard to quantify moderate and vigorous physical activity (MVPA) in pregnant women. The reference standard was based on participant interviews to determine if a woman was an exerciser and confirmed with information obtained from the PAR and a heart rate monitor.

Methods

Fifty-two pregnant women completed a physical activity record (PAR) and wore a SenseWear® Mini Armband (SWA) activity monitor over a 7-day period at 18 weeks gestation. Total minutes spent in MVPA were totaled from both modalities and evaluated against the reference standard using contingency analysis and Pearson's chi-square test to evaluate the number of women meeting minimum prenatal physical activity recommendations (at least 3, 30 minute sessions of exercise per week). Both modalities were also tested individually and collectively to assess their ability as indicators of activity using empirically determined cut-offs as indicated by receiver-operator characteristic curves. These experimentally-derived criteria were also tested with Pearson's chi-square test.

Results

According to the reference standard, 13 of 52 participants (25%) met the criterion of 3, 30 minute sessions of volitional, moderate-intensity activity. When compared to the reference standard, both the PAR and SWA overestimated exercise status; 42 (81%) and 52 (100%) participants, respectively, achieved 90 minutes of MVPA (P < 0.0001 for both comparisons). Single-modality predictors of MVPA did not show a significant correlation. A composite predictor of MVPA offered the most favorable option for sensitivity and specificity (true positives, n = 8 and true negatives, n = 36) using cut-offs of 280 and 385 minutes/week for the PAR and SWA, respectively.

Conclusion

Compared to the reference standard, time spent in MVPA obtained from the PAR or SWA overestimated the prevalence of women meeting prenatal exercise recommendations. The most accurate predictor of women meeting current prenatal exercise guidelines was identified by using the PAR and SWA collectively.
Prognostic significance of a systemic inflammatory response in patients receiving first-line palliative chemotherapy for recurred or metastatic gastric cancer
Authors: Hwang Jun-Eul , Kim Ha-Na , Kim Dae-Eun , Choi Hyun-Jung , Jung Sung-Hoon , Shim Hyun-Jeong , Bae Woo-Kyun , Hwang Eu-Chang , Cho Sang-Hee , Chung Ik-Joo
Published: November 2011

Background

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor prognosis in patients with advanced cancers. We evaluated the relationships between clinical status, laboratory factors and progression free survival (PFS), and overall survival (OS) in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy.

Methods

We reviewed 402 patients with advanced gastric adenocarcinoma who received first-line palliative chemotherapy from June 2004 and December 2009. Various chemotherapy regimens were used. Eastern Cooperative Oncology Group performance status (ECOG PS), C-reactive protein (CRP), albumin, Glasgow prognostic score (GPS), and clinical factors were recorded immediately prior to first-line chemotherapy. Patients with both an elevated CRP (>1.0 mg/dL) and hypoalbuminemia (<3.5 mg/dL) were assigned a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were assigned a GPS of 1, and patients with a normal CRP and albumin were assigned a score of 0. To evaluate the factors that affected PFS and OS, univariate and multivariate analyses were performed.

Results

According to multivariate analysis, the factors independently associated with PFS were ECOG PS (HR 1.37, 95% CI 1.02-1.84, P = 0.035), bone metastasis (HR 1.74, 95% CI 1.14-2.65, P = 0.009), and CRP elevation (HR 1.64, 95% CI 1.28-2.09, P = 0.001). The factors independently associated with OS were ECOG PS (HR 1.33, 95% CI 1.01-1.76, P = 0.037), bone metastasis (HR 1.61, 95% CI 1.08-2.39, P = 0.017), and GPS ≥ 1 (HR 1.76, 95% CI 1.41-2.19, P = 0.001).

Conclusions

The results of this study showed that the presence of a systemic inflammatory response as evidenced by the CRP, GPS was significantly associated with shorter PFS and OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Bone metastasis and GPS were very useful indicator for survival in patients with recurrent or metastatic gastric cancer receiving palliative chemotherapy.
Insulin resistance increases the occurrence of new cardiovascular events in patients with manifest arterial disease without known diabetes. The SMART study
Authors: Verhagen Sandra N , Wassink Annemarie MJ , van der Graaf Yolanda , Gorter Petra M , Visseren Frank LJ ,   the SMART Study Group
Published: November 2011

Background

Insulin resistance is accompanied by a cluster of metabolic changes, often referred to as metabolic syndrome. Metabolic syndrome is associated with an increased cardiovascular risk in patients with manifest arterial disease. We investigated whether insulin resistance is associated with an increased risk for cardiovascular events in patients with manifest arterial disease without known diabetes and whether this can be explained by the components of the metabolic syndrome or by inflammation.

Methods

Prospective cohort study in 2611 patients with manifest arterial disease without known diabetes. Homeostasis model of insulin resistance (HOMA-IR) was used to quantify insulin resistance. The relation of HOMA-IR with cardiovascular events (vascular death, myocardial infarction or stroke) and all cause mortality was assessed with Cox regression analysis. In additional models adjustments were performed for the single components constituting the metabolic syndrome and for inflammation.

Results

HOMA-IR increases with the number of metabolic syndrome components (mean HOMA-IR ± SD in groups with 0, 1, 2, 3, 4 and 5 metabolic syndrome components: 1.4 ± 0.7; 1.8 ± 1.2; 2.4 ± 1.5; 3.1 ± 1.8; 4.0 ± 2.6; and 5.6 ± 3.6 respectively). High HOMA-IR was independently associated with an increased risk of cardiovascular events (tertile 2 vs. 1 HR 1.92; 95%CI 1.20-3.08) (tertile 3 vs.1 HR 1.78; 95%CI 1.10-2.89) and with all cause mortality (tertile 2 vs. 1 HR 1.80; 95%CI 1.04-3.10) (tertile 3 vs.1 HR 1.56; 95%CI 0.88-2.75). These relations were not influenced by the individual components of metabolic syndrome or by inflammation.

Conclusions

In patients with manifest arterial disease without known diabetes, insulin resistance increases with the number of metabolic syndrome components, and elevated insulin resistance increases the risk of new cardiovascular events.
High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction
Authors: Arena Christopher B , Sano Michael B , Rossmeisl John H , Caldwell John L , Garcia Paulo A , Rylander Marissa Nichole , Davalos Rafael V
Published: November 2011

Background

Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death.

Methods

A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation.

Results

No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain.

Conclusions

H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.
HBV inhibits apoB production via the suppression of MTP expression
Authors: Wang Fu-Bing , Zhu Cheng-liang , Liu Xinghui , Gao Guo-sheng
Published: November 2011

Background

Liver dominates the production and secretion of apolipoprotein B (apoB) and evidence shows that liver malfunction induced by hepatitis B virus (HBV) infection could lead to apolipoprotein metabolism disorders. The present study was undertaken to assess the effects of HBV on apoB expression.

Methods

Clinical examination: serum apoB levels in patients with chronic HBV infection and in healthy individuals were measured by immunoturbidimetry using biochemical analyzer Olympus 5400. Cell study: mRNA and protein expression levels of apoB in HepG2 and HepG2.2.15 cells were measured by RT-PCR and Western blot. Alternatively, HBV infectious clone pHBV1.3 or control plasmid pBlue-ks were tranfected into HepG2 cells, and mRNA and protein expression levels of apoB, as well as the microsomal triglyceride transfer protein (MTP) in tranfected HepG2 cells were also measured by RT-PCR and western blot.

Results

Serum apoB level was much lower in chronic HBV patients as compared to healthy individuals (P < 0.05). Expression of apoB mRNA and protein was lower in HepG2.2.15 cells than in HepG2 cells. Similarly, expression of apoB mRNA and protein was lower in pHBV1.3 transfected HepG2 cells than in pBlue-ks transfected HepG2 cells. Expression of MTP mRNA and protein in pHBV1.3 transfected HepG2 cells was reduced in a dose-dependent fashion.

Conclusion

HBV infection plays an inhibitory effect on apoB expression.
Retroperitoneoscopic laparo-endoscopic single-site radical nephrectomy (RLESS-RN): initial experience with a homemade port
Authors: Chung Shiu-Dong , Huang Chao-Yuan , Tsai Yao-Chou , Chueh Shih-Chieh , Hung Shun-Fa , Wang Shuo-Meng , Liao Chun-Hou , Yu Hong-Jeng
Published: November 2011

We successfully performed 6 LESS radical nephrectomy via the retroperitoneal approach (RLESS) using the Alexis wound retractor as a single access with conventional laparoscopic instruments. The results demonstrated that our RLESS technique of radical nephrectomy is a safe and feasible procedure for management of localized renal cancer.
Prevention of abdominal wound infection (PROUD trial, DRKS00000390): study protocol for a randomized controlled trial
Authors: Heger Ulrike , Voss Sabine , Knebel Phillip , Doerr-Harim Colette , Neudecker Jens , Schuhmacher Christoph , Faist Eugen , Diener Markus K , Kieser Meinhard , Seiler Christoph M , Büchler Markus W
Published: November 2011

Background

Wound infection affects a considerable portion of patients after abdominal operations, increasing health care costs and postoperative morbidity and affecting quality of life. Antibacterial coating has been suggested as an effective measure to decrease postoperative wound infections after laparotomies. The INLINE metaanalysis has recently shown the superiority of a slowly absorbable continuous suture for abdominal closure; with PDS plus® such a suture has now been made available with triclosan antibacterial coating.

Methods/Design

The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery. The intervention group will receive triclosan coated polydioxanone sutures, whereas the control group will receive the standard polydioxanone sutures; abdominal closure will otherwise be standardized in both groups. Statistical analysis is based on intention-to-treat population via binary logistic regression analysis, the total sample size of n = 750 is sufficient to ensure alpha = 5% and power = 80%, an interim analysis will be carried out after data of 375 patients are available.

Discussion

The PROUD trial will yield robust data to determine the effectiveness of antibacterial coating in one of the standard sutures for abdominal closure and potentially lead to amendment of current guidelines. The exploration of clinically objective parameters as well as quality of life holds immediate relevance for clinical management and the pragmatic trial design ensures high external validity.

Trial Registration

The trial protocol has been registered with the German Clinical Trials Register (DRKS00000390).
Ten-year experiences with Tracheostomy at a University teaching hospital in Northwestern Tanzania: A retrospective review of 214 cases
Authors: Gilyoma Japhet M , Balumuka Darius D , Chalya Phillipo L
Published: November 2011

Background

Tracheostomy remains a very important life saving surgical procedure worldwide and particularly in our environment where patients present late in upper airway obstruction. Little work has been done on this subject in our environment and therefore it was necessary to conduct this study to describe our own experiences with tracheostomy, outlining the common indications and outcome of tracheostomized patients in our setting and compare our results with those from other centers in the world.

Methods

This was a 10-year retrospective study which was conducted at Bugando Medical Centre from January 2001 to December 2010. Data were retrieved from patients' files kept in the Medical record department and analyzed using SPSS computer software version 15.0. Ethical approval to conduct the study was obtained from relevant authority before the commencement of the study.

Results

A total of 214 patients were studied. The male to female ratio was 3.1: 1. The majority of patients were in the 3rddecade of life. The most common indication for tracheostomy was upper airway obstruction secondary to traumatic causes in 55.1% of patients, followed by upper airway obstruction due to neoplastic causes in 39.3% of cases. The majority of tracheostomies (80.4%) were performed as an emergency. Transverse skin crease incision was employed in all the cases. Post-tracheostomy complication rate was 21.5%. Complication rate was significantly higher in emergency tracheostomy than in electives (P< 0.001). The duration of temporary tracheostomy ranged from 8 days to 46 months, with a median duration of 4 months. Tracheostomy decannulation was successively performed in 72.4% of patients who survived. Mortality rate was 13.6%. The mortality was due to their underlying illnesses, none had tracheostomy-related mortality.

Conclusion

Upper airway obstruction secondary to trauma and laryngeal tumors still remains the most common indication for tracheostomy in our centre and tracheostomy is still a life saving procedure in the surgical management of airway despite complications which are seen more commonly in paediatric patients. Most of tracheostomy related complications can be avoided by meticulous attention to the details of the technique and postoperative tracheostomy care by skilled and trained staff.
Critical assessment of human metabolic pathway databases: a stepping stone for future integration
Authors: Stobbe Miranda D , Houten Sander M , Jansen Gerbert A , van Kampen Antoine HC , Moerland Perry D
Published: November 2011

Background

Multiple pathway databases are available that describe the human metabolic network and have proven their usefulness in many applications, ranging from the analysis and interpretation of high-throughput data to their use as a reference repository. However, so far the various human metabolic networks described by these databases have not been systematically compared and contrasted, nor has the extent to which they differ been quantified. For a researcher using these databases for particular analyses of human metabolism, it is crucial to know the extent of the differences in content and their underlying causes. Moreover, the outcomes of such a comparison are important for ongoing integration efforts.

Results

We compared the genes, EC numbers and reactions of five frequently used human metabolic pathway databases. The overlap is surprisingly low, especially on reaction level, where the databases agree on 3% of the 6968 reactions they have combined. Even for the well-established tricarboxylic acid cycle the databases agree on only 5 out of the 30 reactions in total. We identified the main causes for the lack of overlap. Importantly, the databases are partly complementary. Other explanations include the number of steps a conversion is described in and the number of possible alternative substrates listed. Missing metabolite identifiers and ambiguous names for metabolites also affect the comparison.

Conclusions

Our results show that each of the five networks compared provides us with a valuable piece of the puzzle of the complete reconstruction of the human metabolic network. To enable integration of the networks, next to a need for standardizing the metabolite names and identifiers, the conceptual differences between the databases should be resolved. Considerable manual intervention is required to reach the ultimate goal of a unified and biologically accurate model for studying the systems biology of human metabolism. Our comparison provides a stepping stone for such an endeavor.
Laudation to Prof. Dr. Hans-Toni Ratte--towards conceptual, theory-based ecological science and its transfer to the applied field of ecotoxicology
Authors: Brock Theo , Giesy John P , Heimbach Fred , Hollert Henner , Roß-Nickoll Martina , Schäffer Andreas , Steinhäuser Klaus Günther
Published: November 2011

In order to thank Prof. Dr. Hans-Toni Ratte on the occasion of his retirement for his outstanding experimental and modelling merits in the field of ecotoxicology and ecology and his personal 65th anniversary on November 25th this article will present a laudation.
Integrating body language movements in augmented reality learning environment
Authors: Hsiao Kuei-Fang , Rashvand Habib F
Published: November 2011

Due to excessive use of computer and other low activity learning systems in many schools the physical health status of young students is deteriorating at an alarming rate throughout the world and more seriously in Taiwan upon recent national survey. We address this growing global problem with student learning process in mind in this study we examine making a better use of information technology in virtual really under our new augmented reality (AR) enhanced learning method. Under our AR design/approach we make use of body language by integrating learners' interactions with the computer in their learning based set of physical activities in a way that the effectiveness of the method/technique increases their academic performance through a preference selectivity system. Our results collected from in-school extensive experiments and analysis of the results using recently developed seven multimedia learning subscale factors show that those students who begin with more challenging preferences show more interest and also they gain significantly more in their academic achievements than others.
A human-centric integrated approach to web information search and sharing
Authors: Shtykh Roman Y , Jin Qun
Published: November 2011

In this paper we argue a user has to be in the center of information seeking task, as in any other task where the user is involved. In addition, an essential part of user-centrism is considering a user not only in his/her individual scope, but expanding it to the user's community participation quintessence. Through our research we make an endeavor to develop a holistic approach from how to harnesses relevance feedback from users in order to estimate their interests, construct user profiles reflecting those interests to applying them for information acquisition in online collaborative information seeking context. Here we discuss a human-centric integrated approach for Web information search and sharing incorporating the important user-centric elements, namely a user's individual context and 'social' factor realized with collaborative contributions and co-evaluations, into Web information search.
Human epidermal growth factor receptor bispecific ligand trap RB200: abrogation of collagen-induced arthritis in combination with tumour necrosis factor blockade
Authors: Gompels Luke L , Malik Nasser M , Madden Leigh , Jin Pei , Feldmann Marc , Shepard H Michael , Paleolog Ewa M
Published: November 2011

Introduction

Rheumatoid arthritis (RA) is a chronic disease associated with inflammation and destruction of bone and cartilage. Although inhibition of TNFα is widely used to treat RA, a significant number of patients do not respond to TNFα blockade, and therefore there is a compelling need to continue to identify alternative therapeutic strategies for treating chronic inflammatory diseases such as RA. The anti-epidermal growth factor (anti-EGF) receptor antibody trastuzumab has revolutionised the treatment of patients with EGF receptor-positive breast cancer. Expression of EGF ligands and receptors (known as HER) has also been documented in RA. The highly unique compound RB200 is a bispecific ligand trap that is composed of full-length extracellular domains of HER1 and HER3 EGF receptors. Because of its pan-HER specificity, RB200 inhibits responses mediated by HER1, HER2 and HER3 in vitro and in vivo. The objective of this study was to assess the effect of RB200 combined with TNF blockade in a murine collagen-induced arthritis (CIA) model of RA.

Methods

Arthritic mice were treated with RB200 alone or in combination with the TNF receptor fusion protein etanercept. We performed immunohistochemistry to assess CD31 and in vivo fluorescent imaging using anti-E-selectin antibody labelled with fluorescent dye to elucidate the effect of RB200 on the vasculature in CIA.

Results

RB200 significantly abrogated CIA by reducing paw swelling and clinical scores. Importantly, low-dose RB200 combined with a suboptimal dose of etanercept led to complete abrogation of arthritis. Moreover, the combination of RB200 with etanercept abrogated the intensity of the E-selectin-targeted signal to the level seen in control animals not immunised to CIA.

Conclusions

The human pan-EGF receptor bispecific ligand trap RB200, when combined with low-dose etanercept, abrogates CIA, suggesting that inhibition of events downstream of EGF receptor activation, in combination with TNFα inhibitors, may hold promise as a future therapy for patients with RA.
Detection of autoantibodies to citrullinated BiP in rheumatoid arthritis patients and pro-inflammatory role of citrullinated BiP in collagen-induced arthritis
Authors: Shoda Hirofumi , Fujio Keishi , Shibuya Mihoko , Okamura Tomohisa , Sumitomo Shuji , Okamoto Akiko , Sawada Tetsuji , Yamamoto Kazuhiko
Published: November 2011

Introduction

Anti-citrullinated protein/peptide antibodies (ACPAs) are highly specific to rheumatoid arthritis (RA) patients and are thought to have a close relationship with the pathogenesis of arthritis. Several proteins, including fibrinogen, vimentin, and alpha-enolase, were reported as ACPA-target antigens, and their importance in RA pathogenesis was widely proposed. We identified citrullinated immunoglobulin binding protein (citBiP) as another ACPA target in RA patients and examined its pro-inflammatory role in arthritis.

Methods

We measured the levels of anti-citBiP, anti-BiP, and anti-cyclic citrullinated peptide (CCP) antibodies in the serum of RA patients (n = 100), systemic lupus erythematosus (SLE) patients (n = 60), and healthy controls (n = 30) using ELISA and immunoblotting. Epitope mapping was performed using 27 citBiP-derived peptides. In the mouse study, after DBA/1J mice were immunized with BiP or citBiP, serum titers of ACPAs were measured by ELISA and immunohistochemistry. The development of collagen-induced arthritis (CIA) was observed in BiP- or citBiP-pre-immunized mice.

Results

The serum levels of anti-BiP and anti-citBiP antibodies were significantly increased in RA patients, although only anti-BiP antibodies were slightly increased in SLE patients. Interestingly, anti-citBiP antibody levels were higher than anti-BiP antibody levels in 72% of RA patients, whereas no significant increase in anti-citBiP antibody levels was detected in SLE patients and healthy controls. The serum levels of anti-CCP antibodies were correlated with those of anti-citBiP antibodies in RA patients (R2 = 0.41). Several citrulline residues of citBiP were determined to be major epitopes of anti-citBiP antibodies, one of which showed cross-reactivity with CCP. Immunization of DBA/1J mice with citBiP induced several kinds of ACPAs, including anti-CCP and anti-citrullinated fibrinogen antibodies. Pre-immunization with citBiP exacerbated CIA, and anti-CCP antibody levels were increased in citBiP-pre-immunized CIA mice.

Conclusions

CitBiP is a newly described ACPA target that may play a pro-inflammatory role in arthritis.
Collecting core data in severely injured patients using a consensus trauma template: an international multicentre study
Authors: Ringdal Kjetil Gorseth , Lossius Hans Morten , Jones J Mary , Lauritsen Jens M , Coats Timothy J , Palmer Cameron S , Lefering Rolf , Di Bartolomeo Stefano , Dries David J , Søreide Kjetil ,   The Utstein Trauma Data Collaborators
Published: November 2011

Introduction

No worldwide, standardised definitions exist for documenting, reporting and comparing data from severely injured trauma patients. This study evaluated the feasibility of collecting the data variables of the international consensus-derived Utstein Trauma Template.

Methods

Trauma centres from three different continents were invited to submit Utstein Trauma Template core data during a defined period, for up to 50 consecutive trauma patients. Directly admitted patients with a New Injury Severity Score (NISS) equal to or above 16 were included. Main outcome variables were data completeness, data differences and data collection difficulty.

Results

Centres from Europe (n = 20), North America (n = 3) and Australia (n = 1) submitted data on 965 patients, of whom 783 were included. Median age was 41 years (interquartile range (IQR) 24 to 60), and 73.1% were male. Median NISS was 27 (IQR 20 to 38), and blunt trauma predominated (91.1%). Of the 36 Utstein variables, 13 (36%) were collected by all participating centres. Eleven (46%) centres applied definitions of the survival outcome variable that were different from those of the template. Seventeen (71%) centres used the recommended version of the Abbreviated Injury Scale (AIS). Three variables (age, gender and AIS) were documented in all patients. Completeness > 80% was achieved for 28 variables, and 20 variables were > 90% complete.

Conclusions

The Utstein Template was feasible across international trauma centres for the majority of its data variables, with the exception of certain physiological and time variables. Major differences were found in the definition of survival and in AIS coding. The current results give a clear indication of the attainability of information and may serve as a stepping-stone towards creation of a European trauma registry.
Sepsis induces albuminuria and alterations in the glomerular filtration barrier: a morphofunctional study in the rat
Authors: Adembri Chiara , Sgambati Eleonora , Vitali Luca , Selmi Valentina , Margheri Martina , Tani Alessia , Bonaccini Laura , Nosi Daniele , Caldini Anna L , Formigli Lucia , De Gaudio Angelo R
Published: November 2011

Introduction

Increased vascular permeability represents one of the hallmarks of sepsis. In the kidney, vascular permeability is strictly regulated by the 'glomerular filtration barrier' (GFB), which is comprised of glomerular endothelium, podocytes, their interposed basement membranes and the associated glycocalyx. Although it is likely that the GFB and its glycocalyx are altered during sepsis, no study has specifically addressed this issue. The aim of this study was to evaluate whether albuminuria -- the hallmark of GFB perm-selectivity -- occurs in the initial stage of sepsis and whether it is associated with morphological and biochemical changes of the GFB.

Methods

Cecal ligation and puncture (CLP) was used to induce sepsis in the rat. Tumor necrosis factor (TNF)-alpha levels in plasma and growth of microorganisms in the peritoneal fluid were evaluated at 0, 3 and 7 hours after CLP or sham-operation. At the same times, kidney specimens were collected and structural and ultrastructural alterations in the GFB were assessed. In addition, several components of GFB-associated glycocalyx, syndecan-1, hyluronan (HA) and sialic acids were evaluated by immunofluorescence, immunohistochemistry and lectin histochemistry techniques. Serum creatinine and creatinine clearance were measured to assess kidney function and albuminuria for changes in GFB permeability. Analysis of variance followed by Tukey's multiple comparison test was used.

Results

Septic rats showed increased TNF-alpha levels and growth of microorganisms in the peritoneal fluid. Only a few renal corpuscles had major ultrastructural and structural alterations and no change in serum creatinine or creatinine clearance was observed. Contrarily, urinary albumin significantly increased after CLP and was associated with diffuse alteration in the glycocalyx of the GFB, which consisted in a decrease in syndecan-1 expression and in HA and sialic acids contents. Sialic acids were also changed in their structure, exhibiting a higher degree of acetylation.

Conclusions

In its initial phase, sepsis is associated with a significant alteration in the composition of the GFB-associated glycocalyx, with loss of GFB perm-selectivity as documented by albumin leakage into urine.