bluuebunny/crossref_metadata_2025 huggingface dataset:
Philosophical and Epistemological Issues in Simulation and Gaming
Authors: Grüne-Yanoff Till , Ruphy Stéphanie , Simpson John , Weirich Paul
Published: May 2011

Philosophy finds simulation and gaming intriguing because of the epistemological issues that they raise. For example, how do simulations of a phenomenon help to explain that phenomenon? This collection of essays addresses such issues and hopes to stimulate additional investigations in this fascinating area.
Philosophy and Simulation
Authors: Crookall David
Published: May 2011

We can enhance discussions of simulation by distinguishing between the rationale for using simulation and the philosophical tools for conceptualizing it. I offer my thoughts, inspired by this symposium, on the proposition that simulation is little more than stuff of our minds, a figment of our imagination. I also argue that philosophy is important to all simulation/gaming work.
End-of-Life Care at an Academic Medical Center
Authors: Galanos Anthony Nicholas , Morris Deborah A. , Pieper Carl F. , Poppe-Ries Angela M. , Steinhauser Karen E.
Published: May 2011

Background: End-of-life care is deemed to be poor in the United States – particularly in large teaching hospitals. Via a brief survey, we examined satisfaction with end-of-life care for those patients who died in our academic medical center from provider and family perspectives. Methods: To assess the correlation between overall satisfaction between providers (attending, housestaff, and nurses) as well as family members for decedents who died in our hospital, we conducted a satisfaction survey regarding care in the last three days of life. The nine item survey was administered within 1 week of the patient s death to care providers and approximately 8 to 12 weeks to next of kin. Results: There were 166 deaths examined over the four month study period. Overall satisfaction with care was 3.02 out of 4.0, and differed by respondent group (p= 0.035). Correlation between respondents was very low (range 0.02 to 0.51). The least discordance was between residents and interns (0.5), who had the lowest level of satisfaction (2.72). Housestaff and attendings had the lowest overall correlation in mean satisfaction scores (0.05). Most providers knew their patients for 24 hours or less. Conclusions: Overall satisfaction was high, but there was discordance among different providers. Continuity of care was limited. Age and location of death alone did not significantly affect satisfaction with end-of-life care. Implications of this type of research for improving end of life care at academic centers are discussed.
Support Groups for Adults With Asperger Syndrome
Authors: Jantz Kathryn Mederise
Published: May 2011

A total of 35 adults (24—77 years; 24 males and 11 females) with Asperger syndrome (AS) who were in, were waiting to get in, or had been in support groups participated in the study. In general, the adults were highly educated but unemployed or underemployed and living alone with family members as friends. The participants were interviewed, completed the Autism-Spectrum Quotient questionnaire and the UCLA Loneliness Scale, and rated group experiences. The results of qualitative and quantitative analyses can be interpreted to conclude that participants were lonely and perceived support groups as beneficial for providing (a) social skills and interaction, (b) information and advice, and (c) structure. Participants also reported that someone had encouraged them to attend a support group. This information can help practitioners gain insight into the content and structure of support groups for individuals with AS and may aid in the design of future research on services for adults with AS.
Decreased hippocampal volume, indirectly measured, is associated with depressive symptoms and consolidation deficits in multiple sclerosis
Authors: Kiy Gevrey , Lehmann Pia , Hahn Horst K , Eling Paul , Kastrup Andreas , Hildebrandt Helmut
Published: May 2011

Background: The human hippocampus plays a role in episodic memory and depression. Recently, it has been shown, using manual tracings, that the hippocampus is smaller in volume in MS patients compared with healthy controls, and that, at least for depression, hippocampal atrophy correlates with symptom severity.

Methods: Because manual tracing of the hippocampus is time consuming, we used a semi-automatic procedure for temporal horn volumetry in 72 multiple sclerosis (MS) patients and 16 control subjects as an indirect measure of hippocampal volume. We analysed memory performance with the California Verbal Learning Test (using separate indices for encoding, consolidation and retrieval) and depressive mood with the Beck’s Depression Inventory (distinguishing between psychic and somatic aspects).

Results: MS patients had significantly larger temporal horn volumes and volume correlated with psychic symptoms of depressive mood. Temporal horn volume was also associated with consolidation, in particular in the most impaired group.

Conclusions: Temporal horn volume can be measured relatively easily and appears to correlate with two major clinical problems in MS patients: memory performance and depressive mood. The link between temporal horn volume, consolidation and depression may be hippocampal atrophy, as suggested by their adjacent neuroanatomical localization, and by the similarity in functional loss following impairment of these two structures.
Dynastic parties
Authors: Chhibber Pradeep
Published: May 2011

In the aftermath of the 2009 national elections in India a number of commentators observed that Indian party politics is a dynastic affair. Why is this the case? This paper claims that absence of a party organization, independent civil society associations that mobilize support for the party, and centralized financing of elections has led to the emergence and sustenance of dynastic parties in India. The paper assesses the impact of dynastic parties and shows that not only are party systems more volatile when parties are dynastic but more important, dynastic parties serve to make the political system less representative.
Association of angiotensin I converting enzyme insertion/deletion polymorphism with breast cancer: a meta-analysis
Authors: Sun Meili , Liu Chuanyong , Wei Fang , Zhong Jie , Sun Yuping
Published: May 2011

Background: Polymorphisms of angiotensin I converting enzyme (ACE) gene have been inconsistently associated with breast cancer risk. We examined these associations by performing a meta-analysis.

Materials and methods: Four studies (cases: 1422; controls: 3044) testing the association between ACE insertion/deletion (I/D) polymorphism and breast cancer were examined. The analyses were performed using the Review Manager 5.0.25 software package.

Results: The combined results based on the above four studies showed that there was no significant difference in genotype distribution (DD, ID or II) between breast cancer patients and controls, with the odds ratio (OR) (1.00; 0.94; 1.11) and 95% confidence interval (CI) (0.76 to 1.33; 0.83 to 1.07; 0.96 to 1.28) for DD, ID and II genotype respectively.

Conclusion: The meta-analysis suggests that ACE I/D polymorphism may not be a genetic risk factor for breast cancer.
Microlaparoscopic Hernia Repair in Children
Authors: Turial Salmai , Saied Ahmad , Schier Felix
Published: May 2011

Introduction. This study reports the authors’ experience with the exclusive use of 2-mm instrument sets and small diameter scopes in 100 children undergoing microlaparoscopic herniorrhaphy. Method. This prospective study was designed as a pilot feasibility study; all data related to patients and procedures were prospectively collected. A pneumoperitoneum was established, and 1.7 to 2 mm 0° or 30° scopes were introduced for visualization. Exclusively 2-mm instruments were used. Results. This study included 100 children (aged 15 days to 11 years, median age 2.3 years) undergoing microlaparoscopic hernia repair. A total of 140 hernias were treated. The average operative time for the microlaparoscopically experienced surgeon was 16 minutes for bilateral inguinal hernia and 12 minutes for unilateral hernias. All procedures were completed microlaparoscopically. Hernia recurrence was observed in 2 patients. Conclusion. Based on the authors’ early experience, it is found that microlaparoscopic hernia repair in children seems to be a safe and feasible procedure.
Outcome of axillary nerve injuries treated with nerve grafts
Authors: Okazaki M. , Al-Shawi A. , Gschwind C. R. , Warwick D. J. , Tonkin M. A.
Published: May 2011

This study evaluates the outcome of axillary nerve injuries treated with nerve grafting. Thirty-six patients were retrospectively reviewed after a mean of 53 months (minimum 12 months). The mean interval from injury to surgery was 6.5 months. Recovery of deltoid function was assessed by the power of both abduction and retropulsion, the deltoid bulk and extension lag. The deltoid bulk was almost symmetrical in nine of 34 cases, good in 22 and wasted in three. Grade M4 or M5* was achieved in 30 of 35 for abduction and in 32 of 35 for retropulsion. There was an extension lag in four patients. Deltoid bulk continued to improve with a longer follow-up following surgery. Nerve grafting to the axillary nerve is a reliable method of regaining deltoid function when the lesion is distal to its origin from the posterior cord.
The biomechanical assessment of gap formation after flexor tendon repair using partial interlocking cross-stitch peripheral sutures
Authors: Takeuchi N. , Mitsuyasu H. , Kikuchi K. , Shimoto T. , Higaki H. , Iwamoto Y.
Published: May 2011

The gap formation of five core plus peripheral suture techniques for flexor tendon repair was evaluated by cyclic load testing. Fifty pairs of dental roll tendon models were sutured using six-strand Pennington modified Kessler core suture with 4-0 Polypropylene. One-half or three-fourths circumferential interlocking cross-stitch, or three complete circumferential peripheral suture techniques were performed using 6-0 Polypropylene. An initial cyclic load of 10 N for 500 cycles was applied and increased by 5 N for an additional 500 cycles at each new load until rupture. The complete circumferential interlocking cross-stitch had the greatest fatigue strength. The partial circumferential cross-stitches resulted in significantly larger gap formations at both the repaired and unrepaired sides than the complete circumferential sutures, and were also associated with early rupture. The full circumference of the cut tendon must be sutured using an interlocking cross-stitch peripheral suture to improve strength and avoid gap formation.
Thickened Liquids as a Treatment for Children With Dysphagia and Associated Adverse Effects
Authors: Gosa Memorie , Schooling Tracy , Coleman Jaumeiko
Published: May 2011

Thickened liquids are a common treatment for dysphagia; however, little is known about their effects in children. The aim of this systematic review was to summarize the state and quality of evidence for the use of thickened liquids on swallowing physiology, oral feeding, weight gain/growth, hydration, and pulmonary health outcomes in children with dysphagia. Another aim was to identify any increased occurrence of adverse effects that may be associated with their use in all children, not just those with dysphagia. A total of 24 electronic databases were systematically searched. Articles meeting the inclusion criteria were evaluated for methodological quality by 2 reviewers and vetted by a third. In total, 22 studies were included. Six studies, with significant methodological limitations, examined the effects of thickened liquids on swallowing physiology or pulmonary health outcomes and reported mixed findings. Sixteen studies examined adverse effects and indicated that among a select pediatric population with gastroesophageal reflux, no significant increase in the rate of adverse effects from the use of thickened liquids was noted. Results of this review highlight the insufficient evidence base for this popular treatment option. Additional experimental research is warranted to understand the efficacy and effectiveness of thickened liquid use in the pediatric population.
Novel targeted treatment strategies for refractory chronic lymphocytic leukaemia
Authors: Schnaiter Andrea , Stilgenbauer Stephan
Published: May 2011

Patients with refractory chronic lymphocytic leukaemia (CLL) still have an unfavourable prognosis and novel treatment strategies are necessary, preferably adjusted to the patient’s individual situation. Refractoriness is no longer limited just to fludarabine (F) but extends to F-combinations with other chemotherapeutic agents (e.g. cyclophosphamide [C] and FC) and antibodies (e.g. rituximab [R], FR, and FCR). Also, refractoriness to alemtuzumab is an increasing problem. New pharmacological developments provide promising approaches. This review focuses on novel therapies such as monoclonal antibodies and small molecules aiming at specific targets of the CLL cell in the refractory situation. Approved therapeutic regimens will be presented as well as investigational approaches. An overview of completed and current clinical trials is offered.
Symptom burden and quality of life in patients with follicular lymphoma undergoing maintenance treatment with rituximab compared with observation
Authors: Walker Mark S. , Stepanski Edward J. , Reyes Carolina , Satram-Hoang Sacha , Houts Arthur C. , Schwartzberg Lee S.
Published: May 2011

Background: The impact on health related quality of life (HRQoL) of rituximab maintenance (R-M) versus observation (OBS) after induction for treatment of follicular lymphoma (FL) is unclear.

Methods: We reviewed the charts of 137 patients (53% female, 87% White, age 61.0 ± 12.4 years) who received either R-M ( n = 53) or OBS ( n = 84) after chemotherapy induction for newly diagnosed FL at community oncology practices within the US. Patients (65% with advanced disease; 48% with a high FLIPI score [3–5]) had completed ≥1 Patient Care Monitor HRQoL survey in the period following front-line therapy, and were excluded if they had progressed during front-line therapy.

Results: Linear mixed models showed that postinduction, most symptoms were stable, with patients on R-M reporting HRQoL that was equal to that reported by OBS patients.

Conclusions: Among R-M patients, receipt of rituximab was associated with improved psychological symptoms.
Fast experimental identification of suspension models for control design
Authors: Crivellaro C , Donha D C
Published: May 2011

This paper presents both the theoretical and the experimental approaches of the development of a mathematical model to be used in multi-variable control system designs of an active suspension for a sport utility vehicle (SUV), in this case a light pickup truck. A complete seven-degree-of-freedom model is successfully quickly identified, with very satisfactory results in simulations and in real experiments conducted with the pickup truth. The novelty of the proposed methodology is the use of commercial software in the early stages of the identification to speed up the process and to minimize the need for a large number of costly experiments. The paper also presents major contributions to the identification of uncertainties in vehicle suspension models and in the development of identification methods using the sequential quadratic programming, where an innovation regarding the calculation of the objective function is proposed and implemented.

Results from simulations of and practical experiments with the real SUV are presented, analysed, and compared, showing the potential of the method.
Mitochondrial targeting of human NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2) and its association with early-onset hypertrophic cardiomyopathy and encephalopathy
Authors: Liu Hsin-Yu , Liao Pin-Chao , Chuang Kai-Tun , Kao Mou-Chieh
Published: May 2011

Background

NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2), containing one iron sulfur cluster ([2Fe-2S] binuclear cluster N1a), is one of the core nuclear-encoded subunits existing in human mitochondrial complex I. Defects in this subunit have been associated with Parkinson's disease, Alzheimer's disease, Bipolar disorder, and Schizophrenia. The aim of this study is to examine the mitochondrial targeting of NDUFV2 and dissect the pathogenetic mechanism of one human deletion mutation present in patients with early-onset hypertrophic cardiomyopathy and encephalopathy.

Methods

A series of deletion and point-mutated constructs with the c-myc epitope tag were generated to identify the location and sequence features of mitochondrial targeting sequence for NDUFV2 in human cells using the confocal microscopy. In addition, various lengths of the NDUFV2 N-terminal and C-terminal fragments were fused with enhanced green fluorescent protein to investigate the minimal region required for correct mitochondrial import. Finally, a deletion construct that mimicked the IVS2+5_+8delGTAA mutation in NDUFV2 gene and would eventually produce a shortened NDUFV2 lacking 19-40 residues was generated to explore the connection between human gene mutation and disease.

Results

We identified that the cleavage site of NDUFV2 was located around amino acid 32 of the precursor protein, and the first 22 residues of NDUFV2 were enough to function as an efficient mitochondrial targeting sequence to carry the passenger protein into mitochondria. A site-directed mutagenesis study showed that none of the single-point mutations derived from basic, hydroxylated and hydrophobic residues in the NDUFV2 presequence had a significant effect on mitochondrial targeting, while increasing number of mutations in basic and hydrophobic residues gradually decreased the mitochondrial import efficacy of the protein. The deletion mutant mimicking the human early-onset hypertrophic cardiomyopathy and encephalopathy lacked 19-40 residues in NDUFV2 and exhibited a significant reduction in its mitochondrial targeting ability.

Conclusions

The mitochondrial targeting sequence of NDUFV2 is located at the N-terminus of the precursor protein. Maintaining a net positive charge and an amphiphilic structure with the overall balance and distribution of basic and hydrophobic amino acids in the N-terminus of NDUFV2 is important for mitochondrial targeting. The results of human disease cell model established that the impairment of mitochondrial localization of NDUFV2 as a mechanistic basis for early-onset hypertrophic cardiomyopathy and encephalopathy.
Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4
Authors: Aran Veronica , Bryant Nia J , Gould Gwyn W
Published: May 2011

Background

Insulin stimulates exocytosis of GLUT4 from an intracellular store to the cell surface of fat and muscle cells. Fusion of GLUT4-containing vesicles with the plasma membrane requires the SNARE proteins Syntaxin 4, VAMP2 and the regulatory Sec1/Munc18 protein, Munc18c. Syntaxin 4 and Munc18c form a complex that is disrupted upon insulin treatment of adipocytes. Munc18c is tyrosine phosphorylated in response to insulin in these cells. Here, we directly test the hypothesis that tyrosine phosphorylation of Munc18c is responsible for the observed insulin-dependent abrogation of binding between Munc18c and Syntaxin 4.

Results

We show that Munc18c is directly phosphorylated by recombinant insulin receptor tyrosine kinase in vitro. Using pull-down assays, we show that phosphorylation abrogates binding of Munc18c to both Syntaxin 4 and the v-SNARE VAMP2, as does the introduction of a phosphomimetic mutation into Munc18c (Y521E).

Conclusion

Our data indicate that insulin-stimulated tyrosine phosphorylation of Munc18c impairs the ability of Munc18c to bind its cognate SNARE proteins, and may therefore represent a regulatory step in GLUT4 traffic.
MicroRNA-196a regulates bovine newborn ovary homeobox gene (NOBOX) expression during early embryogenesis
Authors: Tripurani Swamy K , Lee Kyung-Bon , Wee Gabbine , Smith George W , Yao Jianbo
Published: May 2011

Background

Oocyte-derived maternal RNAs drive early embryogenesis when the newly formed embryo is transcriptionally inactive. Recent studies in zebrafish have identified the role of microRNAs during the maternal-to-embryonic transition (MET). MicroRNAs are short RNAs that bind to the 3' UTR of target mRNAs to repress their translation and accelerate their decay. Newborn ovary homeobox gene (NOBOX) is a transcription factor that is preferentially expressed in oocytes and essential for folliculogenesis in mice. NOBOX knockout mice are infertile and lack of NOBOX disrupts expression of many germ-cell specific genes and microRNAs. We recently reported the cloning and expression of bovine NOBOX during early embryonic development and our gene knockdown studies indicate that NOBOX is a maternal effect gene essential for early embryonic development. As NOBOX is a maternal transcript critical for development and NOBOX is depleted during early embryogenesis, we hypothesized that NOBOX is targeted by microRNAs for silencing and/or degradation.

Results

Using an algorithm "MicroInspector", a potential microRNA recognition element (MRE) for miR-196a was identified in the 3' UTR of the bovine NOBOX mRNA. Expression analysis of miR-196a in bovine oocytes and during early embryonic development indicated that it is expressed both in oocytes and embryos and tends to increase at the four-cell and eight-cell stages. Ectopic expression of NOBOX and miR-196a in HeLa cells inhibited the expression of NOBOX protein compared to the control cells without miR-196a. Similarly, the activity of a luciferase construct containing the entire 3' UTR of bovine NOBOX was suppressed, and the regulation was abolished by mutations in the miR-196a binding site indicating that the predicted MRE is critical for the direct and specific binding of miR-196a to the NOBOX mRNA. Furthermore, ectopic expression of miR-196a mimic in bovine early embryos significantly reduced the NOBOX expression at the both mRNA and protein levels.

Conclusion

Collectively, our results demonstrate that miR-196a is a bona fide negative regulator of NOBOX during bovine early embryogenesis.
Low levels of vitamin C in dialysis patients is associated with decreased prealbumin and increased C-reactive protein
Authors: Zhang Kunying , Liu Li , Cheng Xuyang , Dong Jie , Geng Qiuming , Zuo Li
Published: May 2011

Background

Subclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers.

Methods

In this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height2), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis.

Patients were classified into three subgroups by vitamin C level according to previous recommendation [1, 2] in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above).

Results

Patients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups.

Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log10hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects.

Conclusions

The investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is positively associated with serum prealbumin level and negatively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements.
Development and validation of a paediatric long-bone fracture classification. A prospective multicentre study in 13 European paediatric trauma centres
Authors: Schneidmüller Dorien , Röder Christoph , Kraus Ralf , Marzi Ingo , Kaiser Martin , Dietrich Daniel , von Laer Lutz
Published: May 2011

Background

The aim of this study was to develop a child-specific classification system for long bone fractures and to examine its reliability and validity on the basis of a prospective multicentre study.

Methods

Using the sequentially developed classification system, three samples of between 30 and 185 paediatric limb fractures from a pool of 2308 fractures documented in two multicenter studies were analysed in a blinded fashion by eight orthopaedic surgeons, on a total of 5 occasions. Intra- and interobserver reliability and accuracy were calculated.

Results

The reliability improved with successive simplification of the classification. The final version resulted in an overall interobserver agreement of κ = 0.71 with no significant difference between experienced and less experienced raters.

Conclusions

In conclusion, the evaluation of the newly proposed classification system resulted in a reliable and routinely applicable system, for which training in its proper use may further improve the reliability. It can be recommended as a useful tool for clinical practice and offers the option for developing treatment recommendations and outcome predictions in the future.
In vitro antiproliferative activity of partially purified Trigona laeviceps propolis from Thailand on human cancer cell lines
Authors: Umthong Supawadee , Phuwapraisirisan Preecha , Puthong Songchan , Chanchao Chanpen
Published: May 2011

Background

Cancers are some of the leading causes of human deaths worldwide and their relative importance continues to increase. Since an increasing proportion of cancer patients are acquiring resistance to traditional chemotherapeutic agents, it is necessary to search for new compounds that provide suitable specific antiproliferative affects that can be developed as anticancer agents. Propolis from the stingless bee, Trigona laeviceps, is one potential interesting source that is widely available and cultivatable (as bee hives) in Thailand.

Methods

Propolis (90 g) was initially extracted by 95% (v/v) ethanol and then solvent partitioned by sequential extractions of the crude ethanolic extract with 40% (v/v) MeOH, CH2Cl2 and hexane. After solvent removal by evaporation, each extract was solvated in DMSO and assayed for antiproliferative activity against five cancer (Chago, KATO-III, SW620, BT474 and Hep-G2) and two normal (HS27 fibroblast and CH-liver) cell lines using the MTT assay. The cell viability (%) and IC50 values were calculated.

Results

The hexane extract provided the highest in vitro antiproliferative activity against the five tested cancer cell lines and the lowest cytotoxicity against the two normal cell lines. Further fractionation of the hexane fraction by quick column chromatography using eight solvents of increasing polarity for elution revealed the two fractions eluted with 30% and 100% (v/v) CH2Cl2 in hexane (30DCM and 100DCM, respectively) had a higher anti-proliferative activity. Further fractionation by size exclusion chromatography lead to four fractions for each of 30DCM and 100DCM, with the highest antiproliferative activity on cancer but not normal cell lines being observed in fraction# 3 of 30DCM (IC50 value of 4.09 - 14.7 μg/ml).

Conclusions

T. laeviceps propolis was found to contain compound(s) with antiproliferative activity in vitro on cancer but not normal cell lines in tissue culture. The more enriched propolis fractions typically revealed a higher antiproliferative activity (lower IC50 value). Overall, propolis from Thailand may have the potential to serve as a template for future anticancer-drug development.
Identification of Apo-A1 as a biomarker for early diagnosis of bladder transitional cell carcinoma
Authors: Li Hongjie , Li Changying , Wu Huili , Zhang Ting , Wang Jin , Wang Shixin , Chang Jiwu
Published: May 2011

Background

Bladder transitional cell carcinoma (BTCC) is the fourth most frequent neoplasia in men, clinically characterized by high recurrent rates and poor prognosis. Availability of urinary tumor biomarkers represents a convenient alternative for early detection and disease surveillance because of its direct contact with the tumor and sample accessibility.

Results

We tested urine samples from healthy volunteers and patients with low malignant or aggressive BTCC to identify potential biomarkers for early detection of BTCC by two-dimensional electrophoresis (2-DE) coupled with mass spectrometry (MS) and bioinformatics analysis. We observed increased expression of five proteins, including fibrinogen (Fb), lactate dehydrogenase B (LDHB), apolipoprotein-A1 (Apo-A1), clusterin (CLU) and haptoglobin (Hp), which were increased in urine samples of patients with low malignant or aggressive bladder cancer. Further analysis of urine samples of aggressive BTCC showed significant increase in Apo-A1 expression compared to low malignant BTCC. Apo-A1 level was measured quantitatively using enzyme-linked immunosorbent assay (ELISA) and was suggested to provide diagnostic utility to distinguish patients with bladder cancer from controls at 18.22 ng/ml, and distinguish patients with low malignant BTCC from patients with aggressive BTCC in two-tie grading system at 29.86 ng/ml respectively. Further validation assay showed that Apo-A1 could be used as a biomarker to diagnosis BTCC with a sensitivity and specificity of 91.6% and 85.7% respectively, and classify BTCC in two-tie grading system with a sensitivity and specificity of 83.7% and 89.7% respectively.

Conclusion

Taken together, our findings suggest Apo-A1 could be a potential biomarker related with early diagnosis and classification in two-tie grading system for bladder cancer.
Shape and phase control of CdS nanocrystals using cationic surfactant in noninjection synthesis
Authors: Zou Yu , Li Dongsheng , Yang Deren
Published: May 2011

Monodispersed CdS nanocrystals with controllable shape and phase have been successfully synthesized in this study by adding cationic surfactant in noninjection synthesis system. With the increase of the amount of cetyltrimethylammonium chloride (CTAC) added, the shape of the CdS nanocrystals changed from spherical to multi-armed, and the phase changed from zinc-blende to wurtzite. It was found that halide ion Cl- plays a key role in the transformation, and other halide ions such as Br- can also induce similar transformation. We proposed that the strong binding between Cd2+ and halide ions reduced the reactivity of the precursors, decreased the nuclei formed in the nucleation stage, and led to the high concentration of precursor in the growth stage, resulting in the increase of size and phase transformation of CdS nanocrystals. In addition, it was found that the multi-armed CdS nanocrystals lost quantum confinement effect because of the increase of the size with the increase of the concentration of CTAC.
Pathogenesis of lassa fever in cynomolgus macaques
Authors: Hensley Lisa E , Smith Mark A , Geisbert Joan B , Fritz Elizabeth A , Daddario-DiCaprio Kathleen M , Larsen Tom , Geisbert Thomas W
Published: May 2011

Background

Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.

Methods

Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.

Results

Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.

Conclusion

The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.
A systems biology approach to dynamic modeling and inter-subject variability of statin pharmacokinetics in human hepatocytes
Authors: Bucher Joachim , Riedmaier Stephan , Schnabel Anke , Marcus Katrin , Vacun Gabriele , Weiss Thomas S , Thasler Wolfgang E , Nüssler Andreas K , Zanger Ulrich M , Reuss Matthias
Published: May 2011

Background

The individual character of pharmacokinetics is of great importance in the risk assessment of new drug leads in pharmacological research. Amongst others, it is severely influenced by the properties and inter-individual variability of the enzymes and transporters of the drug detoxification system of the liver. Predicting individual drug biotransformation capacity requires quantitative and detailed models.

Results

In this contribution we present the de novo deterministic modeling of atorvastatin biotransformation based on comprehensive published knowledge on involved metabolic and transport pathways as well as physicochemical properties. The model was evaluated on primary human hepatocytes and parameter identifiability analysis was performed under multiple experimental constraints. Dynamic simulations of atorvastatin biotransformation considering the inter-individual variability of the two major involved enzymes CYP3A4 and UGT1A3 based on quantitative protein expression data in a large human liver bank (n = 150) highlighted the variability in the individual biotransformation profiles and therefore also points to the individuality of pharmacokinetics.

Conclusions

A dynamic model for the biotransformation of atorvastatin has been developed using quantitative metabolite measurements in primary human hepatocytes. The model comprises kinetics for transport processes and metabolic enzymes as well as population liver expression data allowing us to assess the impact of inter-individual variability of concentrations of key proteins. Application of computational tools for parameter sensitivity analysis enabled us to considerably improve the validity of the model and to create a consistent framework for precise computer-aided simulations in toxicology.
A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression
Authors: Alloza Eva , Al-Shahrour Fátima , Cigudosa Juan C , Dopazo Joaquín
Published: May 2011

Background

Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs), will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene.

Methods

We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains.

Results

The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents). With the extension of this analysis to an Array-CGH dataset (glioblastomas) from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs.

Conclusions

The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.
Mitochondrial dysfunction in Trypanosoma cruzi: the role of Serratia marcescens prodigiosin in the alternative treatment of Chagas disease
Authors: Genes Carlos , Baquero Eduard , Echeverri Fernando , Maya Juan D , Triana Omar
Published: May 2011

Background

Chagas disease is a health threat for many people, mostly those living in Latin America. One of the most important problems in treatment is the limitation of existing drugs. Prodigiosin, produced by Serratia marcescens (Rhodnius prolixus endosymbiont), belongs to the red-pigmented bacterial prodiginine family, which displays numerous biological activities, including antibacterial, antifungal, antiprotozoal, antimalarial, immunosuppressive, and anticancer properties. Here we describe its effects on Trypanosoma cruzi mitochondria belonging to Tc I and Tc II.

Results

Parasites exposed to prodigiosin altered the mitochondrial function and oxidative phosphorylation could not have a normal course, probably by inhibition of complex III. Prodigiosin did not produce cytotoxic effects in lymphocytes and Vero cells and has better effects than benznidazole. Our data suggest that the action of prodigiosin on the parasites is mediated by mitochondrial structural and functional disruptions that could lead the parasites to an apoptotic-like cell death process.

Conclusions

Here, we propose a potentially useful trypanocidal agent derived from knowledge of an important aspect of the natural life cycle of the parasite: the vector-parasite interaction. Our results indicate that prodigiosin could be a good candidate for the treatment of Chagas disease.
Expression and distribution of PPP2R5C gene in leukemia
Authors: Zheng Haitao , Chen Yu , Chen Shaohua , Niu Yuzhe , Yang Lijian , Li Bo , Lu Yuhong , Geng Suxia , Du Xin , Li Yangqiu
Published: May 2011

Background

Recently, we clarified at the molecular level novel chromosomal translocation t(14;14)(q11;q32) in a case of Sézary syndrome, which caused a rearrangement from TRAJ7 to the PPP2R5C gene. PPP2R5C is one of the regulatory B subunits of protein phosphatase 2A (PP2A). It plays a crucial role in cell proliferation, differentiation, and transformation. To characterize the expression and distribution of five different transcript variants of the PPP2R5C gene in leukemia, we analyzed the expression level of PPP2R5C in peripheral blood mononuclear cells from 77 patients with de novo leukemia, 26 patients with leukemia in complete remission (CR), and 20 healthy individuals by real-time PCR and identified the different variants of PPP2R5C by RT-PCR.

Findings

Significantly higher expression of PPP2R5C was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls. High expression of PPP2R5C was detected in the B-ALL group; however, no significant difference was found compared with the healthy group. The expression level of PPP2R5C in the CML-CR group decreased significantly compared with that in the de novo CML group and was not significantly different from the level in the healthy group. By using different primer pairs that covered different exons, five transcript variants of PPP2R5C could be identified. All variants could be detected in healthy samples as well as in all the leukemia samples, and similar frequencies and distributions of PPP2R5C were indicated.

Conclusions

Overexpression of PPP2R5C in T-cell malignancy as well as in myeloid leukemia cells might relate to its proliferation and differentiation. Investigation of the effect of target inhibition of this gene might be beneficial to further characterization of molecular mechanisms and targeted therapy in leukemia.
CP690,550 inhibits oncostatin M-induced JAK/STAT signaling pathway in rheumatoid synoviocytes
Authors: Migita Kiyoshi , Komori Atsumasa , Torigoshi Takafumi , Maeda Yumi , Izumi Yasumori , Jiuchi Yuka , Miyashita Taiichiro , Nakamura Minoru , Motokawa Satoru , Ishibashi Hiromi
Published: May 2011

Introduction

Interleukin (IL)-6-type cytokines exert their effects through activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade. The JAK/STAT pathways play an important role in rheumatoid arthritis, since JAK inhibitors have exhibited dramatic effects on rheumatoid arthritis (RA) in clinical trials. In this study, we investigated the molecular effects of a small molecule JAK inhibitor, CP690,550 on the JAK/STAT signaling pathways and examined the role of JAK kinases in rheumatoid synovitis.

Methods

Fibroblast-like synoviocytes (FLS) were isolated from RA patients and stimulated with recombinant oncostatin M (OSM). The cellular supernatants were analyzed using cytokine protein chips. IL-6 mRNA and protein expression were analyzed by real-time PCR method and ELISA, respectively. Protein phosphorylation of rheumatoid synoviocytes was assessed by Western blot using phospho-specific antibodies.

Results

OSM was found to be a potent inducer of IL-6 in FLS. OSM stimulation elicited rapid phosphorylation of STATs suggesting activation of the JAK/STAT pathway in FLS. CP690,550 pretreatment completely abrogated the OSM-induced production of IL-6, as well as OSM-induced JAK/STAT, and activation of mitogen-activated kinases (MAPKs) in FLS.

Conclusions

These findings suggest that IL-6-type cytokines contribute to rheumatoid synovitis through activation of the JAK/STAT pathway in rheumatoid synoviocytes. Inhibition of these pro-inflammatory signaling pathways by CP690,550 could be important in the treatment of RA.
Shallow-structure characterization by 2D elastic full-waveform inversion
Authors: Romdhane Anouar , Grandjean Gilles , Brossier Romain , Rejiba Fayçal , Operto Stéphane , Virieux Jean
Published: May 2011

Assessing the effectiveness of elastic full-waveform-inversion (FWI) algorithms when applied to shallow 2D structures in the presence of a complex topography is critically important. By using FWI, we overcome inherent limitations of conventional seismic methods used for near-surface prospecting (acoustic tomography and multichannel spectral analysis of surface waves). The elastic forward problem, formulated in the frequency domain, is based on a mixed finite-element P0-P1 discontinuous Galerkin method to ensure accurate modeling of complex topography effects at a reasonable computing cost. The inversion problem uses an FWI algorithm to minimize the misfit between observed and calculated data. Based on results from a numerical experiment performed on a realistic landslide model inspired from the morphostructure of the Super-Sauze earthflow, we analyzed the effect of using a hierarchical preconditioning strategy, based on a simultaneous multifrequency inversion of damped data, to mitigate the strong nonlinearities coming from the surface waves. This strategy is a key point in alleviating the strong near-surface effects and avoiding convergence toward a local minimum. Using a limited-memory quasi-Newton method improved the convergence level. These findings are analogous to recent applications on large-scale domains, although limited source-receiver offset ranges, low-frequency content of the source, and domination of surface waves on the signal led to some difficulties. Regarding the impact of data decimation on the inversion results, we have learned that an inversion restricted to the vertical data component can be successful without significant loss in terms of parameter imagery resolution. In our investigations of the effect of increased source spacing, we found that a sampling of 4 m (less than three times the theoretical maximum of one half-wavelength) led to severe aliasing.
Role of certain trace minerals in oxidative stress, inflammation, CD4/CD8 lymphocyte ratios and lung function in asthmatic patients
Authors: Guo Chih-Hung , Liu Po-Jen , Hsia Simon , Chuang Chia-Ju , Chen Pei-Chung
Published: May 2011

Background

Asthma is associated with increased inflammation, oxidative stress and abnormal immune system function. We determined the distributions of several essential trace minerals and assessed their relationships to factors that are associated with the pathophysiological status of patients with mild/moderate asthma.

Methods

We enrolled 25 asthmatic patients and 25 healthy subjects. We measured: blood trace minerals, zinc (Zn), copper (Cu) and selenium (Se); oxidative stress markers thiobarbituric acid reactive substances (TBARS); antioxidant enzyme activities; percentages of CD4 and CD8 lymphocyte subsets; high-sensitivity C-reactive protein (hs-CRP); and a lung function index (FEV1/FVC%).

Results

Compared with healthy subjects, asthmatics had lower concentrations of Zn and Se; higher Cu concentrations, and Cu/Zn and Cu/Se ratios; and lower antioxidant enzyme glutathione peroxidase (GPx), glutathione reductase (GR) and catalase activities. Significantly increased concentrations of hs-CRP, TBARS and CD4/CD8 lymphocyte ratios were also observed. Furthermore, plasma TBARS or hs-CRP concentrations were negatively associated with Se concentrations, but were positively associated with Cu/Se ratios. CD4/CD8 lymphocyte ratios were inversely correlated with Se, while it was positively correlated with Cu/Se ratio. FEV1/FVC% was also significantly correlated with Se concentrations, and Cu/Se and Cu/Zn ratios.

Conclusions

Abnormal distributions of these trace minerals may aggravate oxidative damage and inflammation, increased CD4/CD8 lymphocyte ratios and decreased lung function in asthma.
Your Actions Speak Louder than Words when it Comes to Patient Safety; Electrolyte Shortages; Proper Preparation of Multi-chamber Bag
Authors: Cohen Michael R. , Smetzer Judy L.
Published: May 2011

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.