bluuebunny/crossref_metadata_2025 huggingface dataset:
Dimensions of Temperament in Preschoolers Predict Risk Taking and Externalizing Behaviors in Adolescents
Authors: Honomichl Ryan D. , Donnellan M. Brent
Published: June 2011

The present research examines the relation between measures of childhood temperament at 54 months and adolescent risk taking and externalizing problems. Three temperament factors were calculated from maternal reports: negative affectivity, surgency, and effortful control. At Age 15, data was gathered on risk taking and externalizing problems using self- and maternal reports. Analyses indicated that effortful control predicted self-reported risk taking. Different dimensions of temperament were related to externalizing behaviors, depending on the identity of the reporter. Maternal reports of externalizing problems were predicted by all three dimensions, whereas self-reports of externalizing problems were predicted only by surgency. Additional analyses demonstrated that the prospective associations between childhood effortful control and adolescent risk taking and externalizing behaviors were partially mediated by adolescent measures of self-regulation: impulse control and future planning. Collectively, these findings underscore the importance of early emerging personality differences for understanding problem behaviors during the teen years.
Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses
Authors: Karube Kennosuke , Nakagawa Masao , Tsuzuki Shinobu , Takeuchi Ichiro , Honma Keiichiro , Nakashima Yasuhiro , Shimizu Norio , Ko Young-Hyeh , Morishima Yasuo , Ohshima Koichi , Nakamura Shigeo , Seto Masao
Published: June 2011

Oligo-array comparative genomic hybridization (CGH) and gene-expression profiling of natural killer (NK)–cell neoplasms were used in an effort to delineate the molecular pathogenesis involved. Oligo-array CGH identified two 6q21 regions that were most frequently deleted (14 of 39 or 36%). One of these regions included POPDC3, PREP, PRDM1, ATG5, and AIM1, whereas the other included LACE1 and FOXO3. All genes located in these regions, except for POPDC3 and AIM1, were down-regulated in neoplastic samples, as determined by gene-expression analysis, and were therefore considered to be candidate tumor-suppressor genes. A20 and HACE1, the well-known tumor-suppressor genes located on 6q21-23, were included as candidate genes because they also demonstrated frequent genomic deletions and down-regulated expression. The Tet-Off NK cell line NKL was subsequently established for functional analyses. Seven candidate genes were transduced into Tet-Off NKL and forced re-expression was induced. Re-expression of FOXO3 and PRDM1 suppressed NKL proliferation, but this was not the case after re-expression of the other genes. This effect was confirmed using another NK cell line, SNK10. Furthermore, genomic analyses detected nonsense mutations of PRDM1 that led to functional inactivation in one cell line and one clinical sample. PRDM1 and FOXO3 are considered to play an important role in the pathogenesis of NK-cell neoplasms.
Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study
Authors: Thomas Xavier , Elhamri Mohamed , Raffoux Emmanuel , Renneville Aline , Pautas Cécile , de Botton Stéphane , de Revel Thierry , Reman Oumedaly , Terré Christine , Gardin Claude , Chelghoum Youcef , Boissel Nicolas , Quesnel Bruno , Hicheri Yosr , Bourhis Jean-Henri , Fenaux Pierre , Preudhomme Claude , Michallet Mauricette , Castaigne Sylvie , Dombret Hervé
Published: June 2011

To assess the value of administering timed-sequential chemotherapy (TSC; 2 therapeutic sequences separated by a 4-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in consolidation therapy for acute myeloid leukemia (AML), 459 patients 15 to 50 years of age were enrolled in the prospective randomized Acute Leukemia French Association–9802 trial. Complete remission was achieved in 89%. A total of 237 patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the 2 consolidation arms (5-year event-free survival [EFS]: 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML NPM1+ or CEBPA+ and FLT3-ITD− had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; P = .02), especially cytogenetically normal AML (5-year EFS: 48% vs 31%; P = .04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243.
Some inequalities for unitarily invariant norms of matrices
Authors: Wang Shaoheng , Zou Limin , Jiang Youyi
Published: June 2011

This article aims to discuss inequalities involving unitarily invariant norms. We obtain a refinement of the inequality shown by Zhan. Meanwhile, we give an improvement of the inequality presented by Bhatia and Kittaneh for the Hilbert-Schmidt norm.

Mathematical Subject Classification

MSC (2010) 15A60; 47A30; 47B15
On the refinements of the Jensen-Steffensen inequality
Authors: Franjić Iva , Khalid Sadia , Pečarić Josip
Published: June 2011

In this paper, we extend some old and give some new refinements of the Jensen-Steffensen inequality. Further, we investigate the log-convexity and the exponential convexity of functionals defined via these inequalities and prove monotonicity property of the generalized Cauchy means obtained via these functionals. Finally, we give several examples of the families of functions for which the results can be applied.

2010 Mathematics Subject Classification. 26D15.
Boundedness of positive operators on weighted amalgams
Authors: Aguilar Cañestro María Isabel , Ortega Salvador Pedro
Published: June 2011

In this article, we characterize the pairs (u, v) of positive measurable functions such that T maps the weighted amalgam "Equation missing" in (L

p
(u), ℓ
q
) for all "Equation missing", where T belongs to a class of positive operators which includes Hardy operators, maximal operators, and fractional integrals.

2000 Mathematics Subject Classification 26D10, 26D15 (42B35)
Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines
Authors: Wen Chih-Chun , Chen Hui-Ming , Chen Swey-Shen , Huang Li-Ting , Chang Wei-Ting , Wei Wen-Chi , Chou Li-Chen , Arulselvan Palanisamy , Wu Jin-Bin , Kuo Sheng-Chu , Yang Ning-Sun
Published: June 2011

Background

Damage-associated molecular patterns (DAMPs) are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs). Specific microtubule-depolymerizing agents (MDAs) such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs.

Methods

In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues) to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine.

Results

The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT). DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+and NK cells, but not CD4+cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+and CD8+T-cell proliferation when co-cultured with DCs.

Conclusions

Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs) can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine.
Molecular Characterization of Chinese Hamster Cells Mutants Affected in Adenosine Kinase and Showing Novel Genetic and Biochemical Characteristics
Authors: Cui Xianying A , Agarwal Tanvi , Singh Bhag , Gupta Radhey S
Published: June 2011

Background

Two isoforms of the enzyme adenosine kinase (AdK), which differ at their N-terminal ends, are found in mammalian cells. However, there is no information available regarding the unique functional aspects or regulation of these isoforms.

Results

We show that the two AdK isoforms differ only in their first exons and the promoter regions; hence they arise via differential splicing of their first exons with the other exons common to both isoforms. The expression of these isoforms also varied greatly in different rat tissues and cell lines with some tissues expressing both isoforms and others expressing only one of the isoforms. To gain insights into cellular functions of these isoforms, mutants resistant to toxic adenosine analogs formycin A and tubercidin were selected from Chinese hamster (CH) cell lines expressing either one or both isoforms. The AdK activity in most of these mutants was reduced to <5% of wild-type cells and they also showed large differences in the expression of the two isoforms. Thus, the genetic alterations in these mutants likely affected both regulatory and structural regions of AdK. We have characterized the molecular alterations in a number of these mutants. One of these mutants lacking AdK activity was affected in the conserved NxxE motif thereby providing evidence that this motif involved in the binding of Mg2+ and phosphate ions is essential for AdK function. Another mutant, FomR-4, exhibiting increased resistance to only C-adenosine analogs and whose resistance was expressed dominantly in cell-hybrids contained a single mutation leading to Ser191Phe alteration in AdK. We demonstrate that this mutation in AdK is sufficient to confer the novel genetic and biochemical characteristics of this mutant. The unusual genetic and biochemical characteristics of the FomR-4 mutant suggest that AdK in this mutant might be complexed with the enzyme AMP-kinase. Several other AdK mutants were altered in surface residues that likely affect its binding to the adenosine analogs and its interaction with other cellular proteins.

Conclusions

These AdK mutants provide important insights as well as novel tools for understanding the cellular functions of the two isoforms and their regulation in mammalian cells.
Dissecting protein loops with a statistical scalpel suggests a functional implication of some structural motifs
Authors: Regad Leslie , Martin Juliette , Camproux Anne-Claude
Published: June 2011

Background

One of the strategies for protein function annotation is to search particular structural motifs that are known to be shared by proteins with a given function.

Results

Here, we present a systematic extraction of structural motifs of seven residues from protein loops and we explore their correspondence with functional sites. Our approach is based on the structural alphabet HMM-SA (Hidden Markov Model - Structural Alphabet), which allows simplification of protein structures into uni-dimensional sequences, and advanced pattern statistics adapted to short sequences. Structural motifs of interest are selected by looking for structural motifs significantly over-represented in SCOP superfamilies in protein loops. We discovered two types of structural motifs significantly over-represented in SCOP superfamilies: (i) ubiquitous motifs, shared by several superfamilies and (ii) superfamily-specific motifs, over-represented in few superfamilies. A comparison of ubiquitous words with known small structural motifs shows that they contain well-described motifs as turn, niche or nest motifs. A comparison between superfamily-specific motifs and biological annotations of Swiss-Prot reveals that some of them actually correspond to functional sites involved in the binding sites of small ligands, such as ATP/GTP, NAD(P) and SAH/SAM.

Conclusions

Our findings show that statistical over-representation in SCOP superfamilies is linked to functional features. The detection of over-represented motifs within structures simplified by HMM-SA is therefore a promising approach for prediction of functional sites and annotation of uncharacterized proteins.
Turbot reovirus (SMReV) genome encoding a FAST protein with a non-AUG start site
Authors: Ke Fei , He Li-Bo , Pei Chao , Zhang Qi-Ya
Published: June 2011

Background

A virus was isolated from diseased turbotScophthalmus maximusin China. Biophysical and biochemical assays, electron microscopy, and genome electrophoresis revealed that the virus belonged to the genusAquareovirus, and was namedScophthalmus maximusreovirus (SMReV). To the best of our knowledge, no complete sequence of an aquareovirus from marine fish has been determined. Therefore, the complete characterization and analysis of the genome of this novel aquareovirus will facilitate further understanding of the taxonomic distribution of aquareovirus species and the molecular mechanism of its pathogenesis.

Results

The full-length genome sequences of SMReV were determined. It comprises eleven dsRNA segments covering 24,042 base pairs and has the largest S4 genome segment in the sequenced aquareoviruses. Sequence analysis showed that all of the segments contained six conserved nucleotides at the 5' end and five conserved nucleotides at the 3' end (5'-GUUUUA ---- UCAUC-3'). The encoded amino acid sequences share the highest sequence identities with the respective proteins of aquareoviruses in species groupAquareovirusA. Phylogenetic analysis based on the major outer capsid protein VP7 and RNA-dependent RNA polymerase were performed. Members inAquareoviruswere clustered in two groups, one from fresh water fish and the other from marine fish. Furthermore, a fusion associated small transmembrane (FAST) protein NS22, which is translated from a non-AUG start site, was identified in the S7 segment.

Conclusions

This study has provided the complete genome sequence of a novel isolated aquareovirus from marine fish. Amino acids comparison and phylogenetic analysis suggested that SMReV was a new aquareovirus in the species groupAquareovirusA. Phylogenetic analysis among aquareoviruses revealed that VP7 could be used as a reference to divide the aquareovirus from hosts in fresh water or marine. In addition, a FAST protein with a non-AUG start site was identified, which partially contributed to the cytopathic effect caused by the virus infection. These results provide new insights into the virus-host and virus-environment interactions.
Virulence gene profiling of enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli strains: a basis for molecular risk assessment of typical and atypical EPEC strains
Authors: Bugarel Marie , Martin Annett , Fach Patrick , Beutin Lothar
Published: June 2011

Background

Enterohaemorrhagic E. coli (EHEC) can cause severe disease such as bloody diarrhoea and haemolytic uraemic syndrome in humans. Besides production of Shiga toxins, the presence of LEE (eae-gene) and non-LEE (nle) encoded effector genes harboured on O-islands OI-122, OI-71 and OI-57 is associated with EHEC virulence and their frequency in outbreaks. Genes encoded by the EHEC-plasmid are putative virulence markers of EHEC. EHEC-plasmids, LEE and non-LEE effector genes have also been detected in some strains of enteropathogenic E. coli (EPEC). The objective of this study was to analyze the relationship between EHEC and EPEC for virulence genes encoded by genomic O-islands and by the EHEC-plasmids.

Results

Nle genes ent/espL2, nleB and nleE (OI-122), nleA, nleF and nleH1-2 (OI-71), nleG5-2 and nleG6-2 (OI-57), espK (CP-933N) and the EHEC-plasmid encoded genes ehxA, espP, etpD and katP were searched in 73 typical and in 235 atypical enteropathogenic E. coli (EPEC) strains. Typical and atypical EPEC each fall into two clusters. Cluster 1 typical (n = 46) and atypical (n = 129) EPEC strains were characterized by the presence of OI-122 encoded genes and grouped together with 64 investigated EHEC strains. Cluster 2 typical (n = 27) and atypical (n = 106) strains grouped together with 52 LEE-negative, Shiga toxin-producing E. coli (STEC) and with 21 apathogenic E. coli strains. Typical EPEC Cluster 1 strains belonged to serotypes frequently involved in severe illness and outbreaks in children (O111:H2, O114:H2, O55:H6, O127:H6 and O142:H6). Atypical EPEC Cluster 1 strains were characterized by serotypes related to EHEC (O26:H11, O55:H7, O145:H28, O103:H2 and O103:H25).

Conclusion

The OI-122 encoded nleB gene was found to be most closely associated with Cluster 1 strains and may serve as a diagnostic tool for the identification of virulent EHEC and EPEC seropathotypes. OI-71 encoded genes nleA, nleF and nleH1-2 are less associated with Cluster 1 strains. EHEC-plasmid, OI-57 and CP-933 associated genes showed only weak similarities with virulent Cluster 1 EHEC and EPEC strains.
Enhancing the effect of repetitive I-wave paired-pulse TMS (iTMS) by adjusting for the individual I-wave periodicity
Authors: Sewerin Sebastian , Taubert Marco , Vollmann Henning , Conde Virginia , Villringer Arno , Ragert Patrick
Published: June 2011

Background

Repeated application of paired-pulse TMS over the primary motor cortex (M1) in human subjects with an inter-pulse interval (IPI) of 1.5 ms (iTMS1.5 ms) has been shown to significantly increase paired-pulse MEP (ppMEP) amplitudes during the stimulation period and increased single-pulse MEP amplitudes for up to 10 minutes after termination of iTMS.

Results

Here we show in a cross-over design that a modified version of the iTMS1.5 ms protocol with an I-wave periodicity adjusted to the individual I1-peak wave latency (iTMSadj) resulted in a stronger effect on ppMEPs relative to iTMS1.5 ms.

Conclusions

Based on these findings, our results indicate that the efficiency of iTMS strongly depends on the individual choice of the IPI and that parameter optimization of the conventional iTMS1.5 ms protocol might improve the outcome of this novel non-invasive brain stimulation technique.
RETRACTED ARTICLE: Slug down-regulation by RNA interference inhibits invasion growth in human esophageal squamous cell carcinoma
Authors: Tang Peng , Yu Zhentao , Zhang Kejun , Wang Yu , Ma Zhongliang , Zhang Shaoyan , Chen Dong , Zhou Yanbing
Published: June 2011

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cellsin vitroandin vivoin immunodeficient mice.

Methods

We utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assayin vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development.

Results

The EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhihited fewer seeded nodes and demonstrated more apoptosis.

Conclusions

Slug down-regulation promotes cell apoptosis and decreases invasion capabilityin vitroandin vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.
Functional assays to determine the significance of two common XPC 3'UTR variants found in bladder cancer patients
Authors: Qiao Boling , Scott Gina B , Elliott Faye , Vaslin Laurence , Bentley Johanne , Hall Janet , Bishop D Timothy , Knowles Margaret A , Kiltie Anne E
Published: June 2011

Background

XPC is involved in the nucleotide excision repair of DNA damaged by carcinogens known to cause bladder cancer. Individuals homozygous for the variant allele of XPC c.1496C > T (p.Ala499Val) were shown in a large pooled analysis to have an increased bladder cancer risk, and we found two 3'UTR variants, *611T > A and c.*618A > G, to be in strong linkage disequilibrium with c.1496T. Here we determined if these two 3'UTR variants can affect mRNA stability and assessed the impact of all three variants on mRNA and protein expression.

Methods

In vitro mRNA stability assays were performed and mRNA and protein expression measured both in plasmid-based assays and in lymphocytes and lymphoblastoid cell lines from bladder and breast cancer patients.

Results

The two 3'UTR variants were associated with reduced protein and mRNA expression in plasmid-based assays, suggesting an effect on mRNA stability and/or transcription/translation. A near-significant reduction in XPC protein expression (p = 0.058) was detected in lymphoblastoid cell lines homozygous for these alleles but no differences in mRNA stability in these lines was found or in mRNA or protein levels in lymphocytes heterozygous for these alleles.

Conclusion

The two 3'UTR variants may be the variants underlying the association of c.1496C > T and bladder cancer risk acting via a mechanism modulating protein expression.
Down-regulation of NKD1 increases the invasive potential of non-small-cell lung cancer and correlates with a poor prognosis
Authors: Zhang Sheng , Wang Yan , Dai Shun-Dong , Wang En-Hua
Published: June 2011

Background

As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression pattern and clinicopathological significance of NKD1 in patients with non-small-cell lung cancer (NSCLC) is still unclear.

Methods

Immunohistochemical studies were performed on 35 cases of normal lung tissues and 100 cases of NSCLC, including 66 cases with complete follow-up records. The NKD1 protein and mRNA expressions were detected by western blot and Real-time PCR, respectively. To examine the effect of NKD1 on the invasiveness of lung cancer cells, NKD1 was down-regulated by siRNA in lung cancer cell lines and the invasive ability was then evaluated by the Matrigel invasion assay. In addition, the expressions of Dishevelled-1 and β-catenin proteins, as well as MMP mRNA were also examined in NKD1 knockdown cells.

Results

In 35 fresh lung cancer tissues examined, 27(79%) of them exhibited lower levels of NKD1 protein in comparison with their corresponding normal tissue (P = 0.009). However, the NKD1 mRNA level was significantly higher in cancerous lung tissues, compared with the adjacent normal tissues. In 100 NSCLC tissues, NKD1 was significantly lower in 78 cases (78%) than in the normal specimens, determined by immunohistochemical staining. The reduced NKD1 expression was correlated with histological type (P = 0.003), poor differentiation (P = 0.004), lymph node metastasis (P = 0.013), TNM stage (P = 0.002) and poor survival (62.88 ± 3.23 versus 23.61 ± 2.18 months, P = 0.03). In addition, NKD1 knockdown could up-regulate Dishevelled-1 and β-catenin protein levels, as well as increased MMP-7 transcription and the invasive ability of lung cancer cells. Furthermore, when the NKD1-knockdown cells were treated with Dishevelled-1 antibody, their invasive potential was significantly reduced.

Conclusion

NKD1 protein is reduced but NKD1 mRNA is elevated in NSCLC. Reduced NKD1 protein expression correlates with a poor prognosis in NSCLC. NKD1 might inhibit the activity of the canonical Wnt pathway through Dishevelled-1.
Psychological treatment of depressive symptoms in Chinese elderly inpatients with significant medical comorbidity: A meta-analysis
Authors: Dai Bibing , Li Juan , Cuijpers Pim
Published: June 2011

Background

As it is uncertain whether psychological treatments for depressive symptoms are effective in elderly inpatients with significant medical comorbidity, we aimed to assess the treatment effectiveness not only on depressive symptoms but also on somatic symptoms in these inpatients.

Methods

We performed a meta-analysis of randomized controlled studies assessing the effects of psychological treatments in Chinese older inpatients with significant medical comorbidity based upon extensive searches of the most comprehensive computerized Chinese academic database.

Results

The overall effect size for depressive symptoms of twelve studies which compared psychological treatments with a care-as-usual control group was d = 0.80 (95% Confidence Intervals (CI) = 0.60-0.99; p < 0.001). The relative risk of psychological intervention of being effective or not, compared to control condition, was 1.52 (95% CI = 1.25-1.85; p < 0.001).

Conclusions

We conclude that psychological treatments of depressive symptoms are effective for Chinese elderly inpatients with significant medical comorbidity which should receive more attention in medical settings.
Cross-sectional evaluation of the periapical status as related to quality of root canal fillings and coronal restorations in a rural adult male population of Turkey
Authors: Gündüz Kaan , Avsever Hakan , Orhan Kaan , Demirkaya Kadriye
Published: June 2011

Background

To determine the prevalence of periapical lesions in root canal-treated teeth in a rural, male adult, Turkish population and to investigate the influence of the quality of root canal fillings on prevalence of periapical lesions.

Methods

The sample for this cross-sectional study consisted of 552 adult male patients, 18-32 years of age, presenting consecutively as new patients seeking routine dental care at the Dental Sciences of Gulhane Military Medicine, Ankara. The radiographs of the 1014 root canal-treated teeth were evaluated. The teeth were grouped according to the radiographic quality of the root canal filling and the coronal restoration. The criteria used for the examination were slightly modified from those described by De Moor. Periapical status was assessed by the Periapical Index scores (PAI) proposed by Orstavik.

Results

The overall success rate of root canal treatment was 32.1%. The success rates of adequately root canal treatment were significantly higher than inadequately root canal treatment, regardless of the quality or presence of the coronal restoration (P < .001). In addition, the success rate of inadequate root canal treatment was also significantly affected by the quality of coronal restorations.

Conclusions

Our results revealed a high prevalence of periapical lesions in root canal treatment, which is comparable to that reported in other methodologically compatible studies from diverse geographical locations. In addition, the results from the present study confirm the findings of other studies that found the quality of the root canal treatment to be a key factor for prognosis with or without adequate coronal restoration.
The interleukin-6 and noradrenaline mediated inflammation-stress feedback mechanism is dysregulated in metabolic syndrome: Effect of exercise
Authors: Martín-Cordero Leticia , García Juan J , Hinchado Maria D , Ortega Eduardo
Published: June 2011

Background

Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and "low grade inflammation", with the concomitant increased risk of cardiovascular events. Removal of the inflammatory mediator signals is a promising strategy to protect against insulin resistance, obesity, and other problems associated with MS such as cardiovascular disease. The aim of the present investigation was to determine the "inflammatory and stress status" in an experimental model of MS, and to evaluate the effect of a program of habitual exercise and the resulting training-induced adaptation to the effects of a single bout of acute exercise.

Methods

Obese Zucker rats (fa/fa) were used as the experimental model of MS, and lean Zucker rats (Fa/fa) were used for reference values. The habitual exercise (performed by the obese rats) consisted of treadmill running: 5 days/week for 14 weeks, at 35 cm/s for 35 min in the last month. The acute exercise consisted of a single session of 25-35 min at 35 cm/s. Circulating concentrations of IL-6 (a cytokine that regulates the inflammatory and metabolic responses), CRP (a systemic inflammatory marker), and corticosterone (CTC) (the main glucocorticoid in rats) were determined by ELISA, and that of noradrenaline (NA) was determined by HPLC. Glucose was determined by standard methods.

Results

The genetically obese animals showed higher circulating levels of glucose, IL-6, PCR, and NA compared with the control lean animals. The habitual exercise program increased the concentration of IL-6, PCR, NA, and glucose, but decreased that of CTC. Acute exercise increased IL-6, CRP, and NA in the sedentary obese animals, but not in the trained obese animals. CTC was increased after the acute exercise in the trained animals only.

Conclusion

Animals with MS present a dysregulation in the feedback mechanism between IL-6 and NA which can contribute to the systemic low-grade inflammation and/or hyperglycaemia of MS. An inappropriate exercise intensity can worsen this dysregulation, contributing to the metabolic, inflammatory, and stress disorders associated with MS. Habitual exercise (i.e., training) induces a positive adaptation in the response to acute exercise.
Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda
Authors: De Beaudrap Pierre , Nabasumba Carolyn , Grandesso Francesco , Turyakira Eleanor , Schramm Birgit , Boum Yap , Etard Jean-François
Published: June 2011

Background

Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection.

Methods

Two cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed.

Results

In 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors.

Conclusions

This study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.
Dietary red palm oil supplementation decreases infarct size in cholesterol fed rats
Authors: Szucs Gergo , Bester Dirk J , Kupai Krisztina , Csont Tamas , Csonka Csaba , Esterhuyse Adriaan J , Ferdinandy Peter , Van Rooyen Jacques
Published: June 2011

Background and Aims

The effect of red palm oil (RPO) supplementation on infarct size after ischaemia/reperfusion in a cholesterol enriched diet-induced hyperlipidemic animal model has not been reported. Previous studies reported results on the effect of RPO in a normal diet, whilst evidence of protection has been linked to improved functional recovery, prosurvival kinase, anti-apoptosis and NO-cGMP. Therefore, we aimed to investigate the effects of dietary RPO supplementation in a cholesterol-enriched diet-induced hyperlipidemic rat model and to investigate the involvement of matrix metalloproteinase 2 (MMP2) inhibition as a possible mechanism of protection.

Materials and Methods

Male Wistar rats were fed either a standard rat chow diet (Norm) or a 2% cholesterol-enriched diet (Chol) for nine weeks. Additionally, two more groups received the same treatment, however, at the week 4, diet was supplemented with RPO for the last five weeks (Norm+RPO and Chol+RPO), respectively. After the feeding period hearts were isolated, perfused according to Langendorff and subjected to 30 minutes of normothermic global ischaemia followed by two hours of reperfusion. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining at the end of reperfusion.

Results

Cholesterol-enriched diet increased myocardial infarct size from 23.5 ± 3.0% to 37.2 ± 3.6% (p < 0.05) when compared to normal diet. RPO supplementation significantly reduced infarct size either in Norm+RPO or in Chol+RPO (to 9.2 ± 1.0% and 26.9 ± 3.0%), respectively. Infarct size in Chol+RPO was comparable to the Norm group. MMP2 activity before ischaemia was significantly reduced in the Chol+RPO group when compared to the Chol group. However, the MMP2 activity of the hearts of the RPO fed rats was significantly increased when compared to the normal diet group after ischaemia.

Conclusions

For the first time it was shown that dietary RPO supplementation attenuated the increased susceptibility of the hearts in cholesterol fed rats to ischaemia/reperfusion injury. This was shown by reduced infarct size. For the first time we also show that red palm oil supplementation altered pre-ischaemic levels of MMP-2, which may indicate that myocardial MMP2 may be implicated as a possible role player in RPO mediated protection against ischaemia/reperfusion injury in hearts of cholesterol supplemented rats.
Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy
Authors: Arienti Chiara , Tesei Anna , Verdecchia Giorgio Maria , Framarini Massimo , Virzì Salvatore , Grassi Antonio , Scarpi Emanuela , Turci Livia , Silvestrini Rosella , Amadori Dino , Zoli Wainer
Published: June 2011

Background

Platinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world. The aim of the present study was to compare the advantages and limits of a conventional chemosensitivity test with those of new biomolecular markers in predicting response to platinum regimens in a series of patients with peritoneal carcinomatosis from ovarian cancer.

Methods

Fresh surgical biopsy specimens were obtained from 30 patients with primary or recurrent peritoneal carcinomatosis from ovarian cancer. ERCC1, GSTP1, MGMT, XPD, and BRCA1 gene expression levels were determined by Real-Time RT-PCR. An in vitro chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient.

Results

MGMT and XPD expression was directly and significantly related to resistance to platinum-containing treatment (p = 0.036 and p = 0.043, respectively). Significant predictivity in terms of sensitivity and resistance was observed for MGMT expression (75.0% and 72.5%, respectively; p = 0.03), while high predictivity of resistance (90.9%) but very low predictivity of sensitivity (37.5%) (p = 0.06) were observed for XPD. The best overall and significant predictivity was observed for chemosensitivity test results (85.7% sensitivity and 91.3% resistance; p = 0.0003).

Conclusions

The in vitro assay showed a consistency with results observed in vivo in 27 out of the 30 patients analyzed. Sensitivity and resistance profiles of different drugs used in vivo would therefore seem to be better defined by the in vitro chemosensitivity test than by expression levels of markers.
Long- term outcome of paediatric patients with ANCA vasculitis
Authors: Arulkumaran Nishkantha , Jawad Susan , Smith Stuart W , Harper Lorraine , Brogan Paul , Pusey Charles D , Salama Alan D
Published: June 2011

Background

Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment- related morbidity and mortality is important. The aim of this study is to describe the long- term clinical course of paediatric patients with ANCA vasculitis.

Methods

The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis.

Results

We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only.

Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy.

Conclusion

Close long- term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease- related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group of patients. In addition, although not yet observed in our series, late cardiovascular morbidity remains a major longer-term potential concern for adult survivors of paediatric vasculitis.
Resistance to thyroid hormone associated with a novel mutation of the thyroid β receptor gene in a four-year-old female
Authors: Canadas Karina T , Rivkees Scott A , Udelsman Robert , Breuer Christopher K
Published: June 2011

Resistance to thyroid hormone (RTH) is a rare syndrome of reduced responsiveness of target tissues to thyroid hormone and is caused mutation in the thyroid β receptor gene. We report a novel mutation, E445X, causing RTH in a 4-year old girl. The patient exhibited extreme signs and symptoms of RTH at an early age, and had a large compressive goiter. Following total extracapsular thyroidectomy, upper airway compression was relieved and symptoms of hyperthyroidism improved. This case appears to be the youngest child recorded to have undergone total thyroidectomy for RTH. Post-operative TSH elevations were managed with every-other-day triiodothyronine therapy.
Interactomes, manufacturomes and relational biology: analogies between systems biology and manufacturing systems
Authors: Rietman Edward A , Colt John Z , Tuszynski Jack A
Published: June 2011

Background

We review and extend the work of Rosen and Casti who discuss category theory with regards to systems biology and manufacturing systems, respectively.

Results

We describe anticipatory systems, or long-range feed-forward chemical reaction chains, and compare them to open-loop manufacturing processes. We then close the loop by discussing metabolism-repair systems and describe the rationality of the self-referential equationf=f(f). This relationship is derived from some boundary conditions that, in molecular systems biology, can be stated as the cardinality of the following molecular sets must be about equal: metabolome, genome, proteome. We show that this conjecture is not likely correct so the problem of self-referential mappings for describing the boundary between living and nonliving systems remains an open question. We calculate a lower and upper bound for the number of edges in the molecular interaction network (the interactome) for two cellular organisms and for two manufacturomes for CMOS integrated circuit manufacturing.

Conclusions

We show that the relevant mapping relations may not be Abelian, and that these problems cannot yet be resolved because the interactomes and manufacturomes are incomplete.
Identification of serum biomarkers for aging and anabolic response
Authors: Banerjee Camellia , Ulloor Jagadish , Dillon Edgar L , Dahodwala Qusai , Franklin Brittani , Storer Thomas , Sebastiani Paola , Sheffield-Moore Melinda , Urban Randall J , Bhasin Shalender , Montano Monty
Published: June 2011

Objective

With the progressive aging of the human population, there is an inexorable decline in muscle mass, strength and function. Anabolic supplementation with testosterone has been shown to effectively restore muscle mass in both young and elderly men. In this study, we were interested in identifying serum factors that change with age in two distinct age groups of healthy men, and whether these factors were affected by testosterone supplementation.

Methods

We measured the protein levels of a number of serum biomarkers using a combination of banked serum samples from older men (60 to 75 years) and younger men (ages 18 to 35), as well as new serum specimens obtained through collaboration. We compared baseline levels of all biomarkers between young and older men. In addition, we evaluated potential changes in these biomarker levels in association with testosterone dose (low dose defined as 125 mg per week or below compared to high dose defined as 300 mg per week or above) in our banked specimens.

Results

We identified nine serum biomarkers that differed between the young and older subjects. These age-associated biomarkers included: insulin-like growth factor (IGF1), N-terminal propeptide of type III collagen (PIIINP), monokine induced by gamma interferon (MIG), epithelial-derived neutrophil-activating peptide 78 (ENA78), interleukin 7 (IL-7), p40 subunit of interleukin 12 (IL-12p40), macrophage inflammatory protein 1β (MIP-1β), platelet derived growth factor β (PDGFβ) and interferon-inducible protein 10 (IP-10). We further observed testosterone dose-associated changes in some but not all age related markers: IGF1, PIIINP, leptin, MIG and ENA78. Gains in lean mass were confirmed by dual energy X-ray absorptiometry (DEXA).

Conclusions

Results from this study suggest that there are potential phenotypic biomarkers in serum that can be associated with healthy aging and that some but not all of these biomarkers reflect gains in muscle mass upon testosterone administration.
Isolation and characterization of a novel alphanodavirus
Authors: Bai Huimin , Wang Yun , Li Xiang , Mao Haitao , Li Yan , Han Shili , Shi Zhengli , Chen Xinwen
Published: June 2011

Background

Nodaviridae is a family of non-enveloped isometric viruses with bipartite positive-sense RNA genomes. The Nodaviridae family consists of two genera: alpha- and beta-nodavirus. Alphanodaviruses usually infect insect cells. Some commercially available insect cell lines have been latently infected by Alphanodaviruses.

Results

A non-enveloped small virus of approximately 30 nm in diameter was discovered co-existing with a recombinant Helicoverpa armigera single nucleopolyhedrovirus (Hear NPV) in Hz-AM1 cells. Genome sequencing and phylogenetic assays indicate that this novel virus belongs to the genus of alphanodavirus in the family Nodaviridae and was designated HzNV. HzNV possesses a RNA genome that contains two segments. RNA1 is 3038 nt long and encodes a 110 kDa viral protein termed protein A. The 1404 nt long RNA2 encodes a 44 kDa protein, which exhibits a high homology with coat protein precursors of other alphanodaviruses. HzNV virions were located in the cytoplasm, in association with cytoplasmic membrane structures. The host susceptibility test demonstrated that HzNV was able to infect various cell lines ranging from insect cells to mammalian cells. However, only Hz-AM1 appeared to be fully permissive for HzNV, as the mature viral coat protein essential for HzNV particle formation was limited to Hz-AM1 cells.

Conclusion

A novel alphanodavirus, which is 30 nm in diameter and with a limited host range, was discovered in Hz-AM1 cells.
Prednisolone and acupuncture in Bell's palsy: study protocol for a randomized, controlled trial
Authors: Xia Feng , Han Junliang , Liu Xuedong , Wang Jingcun , Jiang Zhao , Wang Kangjun , Wu Songdi , Zhao Gang
Published: June 2011

Background

There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients.

Methods/Design

In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period.

Discussion

The result of this trial will assess the efficacy of using prednisolone and staging acupuncture to treat Bell's palsy, and to determine a best combination therapy with prednisolone and acupuncture for treating Bell's palsy.

Trial Registration

ClinicalTrials.gov: NCT01201642