bluuebunny/crossref_metadata_2025 huggingface dataset:
Three monoclonal antibodies against the serpin protease nexin-1 prevent protease translocation
Authors: Kousted Tina M. , Skjoedt Karsten , Petersen Steen V. , Koch Claus , Vitved Lars , Sochalska Maja , Lacroix Céline , Andersen Lisbeth M. , Wind Troels , Andreasen Peter A. , Jensen Jan K.
Published: October 2013

Protease nexin-1 (PN-1) belongs to the serpin family and is an inhibitor of thrombin, plasmin, urokinase-type plasminogen activator, and matriptase. Recent studies have suggested PN-1 to play important roles in vascular-, neuro-, and tumour-biology. The serpin inhibitory mechanism consists of the serpin presenting its so-called reactive centre loop as a substrate to its target protease, resulting in a covalent complex with the inactivated enzyme. Previously, three mechanisms have been proposed for the inactivation of serpins by monoclonal antibodies: steric blockage of protease recognition, conversion to an inactive conformation or induction of serpin substrate behaviour. Until now, no inhibitory antibodies against PN-1 have been thoroughly characterised. Here we report the development of three monoclonal antibodies binding specifically and with high affinity to human PN-1. The antibodies all abolish the protease inhibitory activity of PN-1. In the presence of the antibodies, PN-1 does not form a complex with its target proteases, but is recovered in a reactive centre cleaved form. Using site-directed mutagenesis, we mapped the three overlapping epitopes to an area spanning the gap between the loop connecting α-helix F with β-strand 3A and the loop connecting α-helix A with β-strand 1B. We conclude that antibody binding causes a direct blockage of the final critical step of protease translocation, resulting in abortive inhibition and premature release of reactive centre cleaved PN-1. These new antibodies will provide a powerful tool to study the in vivo role of PN-1’s protease inhibitory activity.
Flow Reversal Versus Filter Protection
Authors: de Castro-Afonso Luis Henrique , Abud Lucas Giansante , Rolo Jaicer Gonçalves , dos Santos Antônio Carlos , de Oliveira Lívia , Barreira Clara Monteiro Antunes , Velasco Tonicarlo Rodrigues , Pontes-Neto Octávio Marques , Abud Daniel Giansante
Published: October 2013

Background—

Carotid artery stenting (CAS) has become an alternative treatment for patients presenting symptomatic carotid artery stenosis. The improvement in clinical outcomes with CAS has been associated with the development of embolic protection devices. The trial aim is to compare flow reversal versus filter protection during CAS through femoral access.

Methods and Results—

Patients were randomly enrolled in CAS using flow reversal or filter protection. The primary end points were the incidence, number, and size of new ischemic brain lesions after CAS. The secondary end points included major adverse cardiac and cerebrovascular events, transient ischemic attack, and definitive ischemic brain lesions on fluid-attenuated inversion recovery magnetic resonance image at a 3-month follow-up. Ischemic brain lesions were assessed by a 3T magnetic resonance image. Neurological outcomes were evaluated by means of the National Institutes of Health Stroke Scale and the modified Rankin Scale (mRS). Forty consecutive patients were randomly assigned. Compared with flow reversal (n=21), filter protection (n=19) resulted in a significant reduction in the incidence (15.8% versus 47.6%,
P
=0.03), number (0.73 versus 2.6,
P
=0.05), and size (0.81 versus 2.23 mm,
P
=0.05) of new ischemic brain lesions. Two patients, 1 from each group, presented transient ischemic attack at 3-month follow-up. There were no major adverse cardiac and cerebrovascular events in the hospital or at 3-month follow-up.

Conclusions—

In this small sample size trial, filter protection was more effective than flow reversal in reducing ischemic brain lesions during CAS through femoral approach.

Clinical Trial Registration—

URL:
http://portal2.saude.gov.br/sisnep/
. Unique identifier: 0538.0.004.000-10.
Inhibition of Four-and-a-Half LIM Domain Protein-2 Increases Survival, Migratory Capacity, and Paracrine Function of Human Early Outgrowth Cells Through Activation of the Sphingosine Kinase-1 Pathway
Authors: Ebrahimian Talin , Arfa Omar , Simeone Stefania , Lemarié Catherine A. , Lehoux Stéphanie , Wassmann Sven
Published: October 2013

Rationale:

Inhibition of four-and-a-half LIM domain protein-2 (FHL2) attenuates atherosclerotic lesion formation and increases endothelial cell migration. Early outgrowth cells (EOCs) contribute substantially to endothelial repair.

Objective:

We investigated the role of FHL2 in the regulation of EOCs.

Methods and Results:

Human EOCs were cultured from peripheral blood. FHL2 knockdown in EOCs by siRNA resulted in increased EOC numbers and reduced apoptosis, as indicated by decreased cleaved caspase-III and reduced Bax/Bcl-2 expression ratio. This was mediated through increased phosphorylation and membrane translocation of sphingosine kinase-1, increased sphingosine-1-phosphate levels, and Akt phosphorylation. FHL2 knockdown increased stromal cell–derived factor-1–induced EOC migration through upregulation of αv/β3, αv/β5, and β2 integrins, associated with increased cortactin expression. Reduced apoptosis, increased EOC migration, and cortactin upregulation by FHL2 siRNA were prevented by CAY10621, the sphingosine kinase-1 inhibitor, and the sphingosine-1-phosphate receptor-1/-3 antagonist VPC23019. These findings were confirmed using spleen-derived EOCs from FHL2
−/−
mice. Apoptosis was decreased and migration increased in endothelial cells exposed to the conditioned medium of FHL2
−/−
versus wild-type (WT) EOCs. These paracrine effects were abolished by VPC23019. Importantly, reendothelialization after focal carotid endothelial injury in WT mice was significantly increased after intravenous injection of FHL2
−/−
versus WT EOCs.

Conclusions:

Our findings suggest that FHL2 negatively regulates EOC survival, migration, and paracrine function. FHL2 inhibition in EOCs reduces apoptosis and enhances survival and migratory capacity of both EOCs and surrounding endothelial cells by activation of the sphingosine kinase-1/sphingosine-1-phosphate pathway, resulting in improvement of endothelial regeneration.
Twenty-Year Trends in Long-Term Mortality Risk in 17 149 Survivors of Ischemic Stroke Less Than 55 Years of Age
Authors: Giang Kok Wai , Björck Lena , Nielsen Susanne , Novak Masuma , Sandström Tatiana Zverkova , Jern Christina , Torén Kjell , Rosengren Annika
Published: October 2013

Background and Purpose—

The purpose of the present study was to investigate the 4-year mortality risk among patients <55 years with a first ischemic stroke during 1987–2006.

Methods—

A total of 17 149 cases (37.4% women) aged 18 to 54 years who survived ≥28 days after a first ischemic stroke were identified in the Swedish Inpatient Register from 1987 to 2006. All patients were followed for 4 years or until death. The standardized mortality ratio was calculated by comparing the mortality rates with those of the general population of equivalent age, sex, and calendar year.

Results—

During the period, there were 1265 deaths. Long-term survival improved over time in both men and women. Among men, the mortality risk decreased by 32% (hazard ratio=0.68 [95% confidence interval, 0.56–0.82]) from the first 5-year period to the last 5-year period (1987–1991 versus 2002–2006), and among women, the mortality risk decreased by 45% (0.55 [0.41–0.75]). Despite an overall decrease in mortality, the standardized mortality ratios for the last 5-year period remained high: 5.88 (95% confidence interval, 5.10–6.71) for men and 5.91 (4.68–7.29) for women with an absolute excess risk of 1.60 and 0.97 per 100 person-years, respectively, with nearly half of all deaths related to cardiovascular disease.

Conclusions—

During the 20-year period, 4-year mortality decreased by one third but was still 6-fold higher than that of the general population in the most recent period, emphasizing the importance of secondary prevention in young persons who have had a stroke.
The Devil is Red: Socialist Satanism in the Nineteenth Century
Authors: Faxneld Per
Published: October 2013

Abstract

During the nineteenth century, socialists all over the Western world employed Satan as a symbol of the workers’ emancipation from capitalist tyranny and the toppling of the Christian Church, which they perceived as a protector of this oppressive system. Starting with the English Romantics at the end of the eighteenth century, European radicals developed a discourse of symbolic Satanism, which was put to use by major names in socialism like Godwin, Proudhon, and Bakunin. This shock tactic became especially widespread in turn-of-the-century Sweden, and accordingly the article focuses on the many examples of explicit socialist Satanism in that country. They are contextualized by showing the parallels to, among other things, use of Lucifer as a positive symbol in the realm of alternative spirituality, specifically the Theosophical Society. A number of reasons for why Satan gained such popularity among socialists are suggested, and the sometimes blurry line separating the rhetoric of symbolic Satanism from actual religious writing is scrutinized.
A new genus of Arietelloidea (Copepoda, Calanoida), Frankferrarius, from deep waters of the Atlantic Ocean
Authors: Markhaseva Elena L.
Published: October 2013

A new calanoid copepod genusFrankferrariusis based on the female and male of a new species described herein. The specimens were collected in the North and South Atlantic from abyssal depths close to the sea bed during the German expedition DIVA III in 2009.Frankferrarius admirabilisgen. et sp. nov. is a representative of the superfamily Arietelloidea with the praecoxal arthrite of the maxillule heavily sclerotized and a highly specialized, huge maxilla with a well-pronounced articulation between the coxa and basis and with long, grouped endopod setae apparently designed for piercing and grasping prey. This new genus,Frankferrarius, does not completely fit any known family of the Arietelloidea, but is provisionally placed in the Augaptilidae as it shares with this family the general pattern of segmentation and setation of its swimming legs, and a single genital operculum positioned medially on the ventral part of the genital double-somite.
Microscopic and cytochemical characterisation of haemocytes of the mud crab Scylla serrata (Forskål, 1775) (Decapoda, Portunidae)
Authors: Kumar Brajendu , Deepika A. , Arumugam M. , Mullainadhan P. , Makesh M. , Tripathi Gayatri , Purushothaman C. S. , Rajendran K. V.
Published: October 2013

Haemocytes of the mud crab Scylla serrata (Forskål, 1775) were characterised based on morphological features using light and electron microscopy, and cytochemistry. The cells were identified as hyaline, semigranular and granular haemocytes. Hyaline cells were the smallest haemocytes among the three types identified, having the highest nucleo-cytoplasmic ratio. The cells showed a number of cytoplasmic organelles and also contained a few small as well as large-sized granules. Semigranular haemocytes possessed moderate numbers of large-sized granules or numerous small-sized granules and comparatively less numbers of organelles. Granular haemocytes were the largest haemocytes with the lowest nucleo-cytoplasmic ratio and contained many large-sized granules. Cytoplasmic organelles were least observed in the granular haemocytes. These three haemocyte morphotypes constituted 60, 21 and 19%, respectively, of the total haemocyte population, while the total haemocyte count was 7.31 × 106 to 7.18 × 107 with a mean of 2.86 × 107 cells ml−1. In cytochemical studies performed to localize carbohydrates, lipids and prophenol oxidase, all the haemocyte types were positive for PAS and toluidine blue, indicating the presence of mucopolysaccharides, whereas semigranular and granular haemocytes were rich in carbohydrates and lipid moieties. Besides, prophenol oxidase was localised within the granules of semigranular and granular haemocytes. Hyaline haemocytes showed an abundance of well differentiated cytoplasmic organelles and granules, and there was a distinct differentiation between semigranular and granular haemocytes in terms of granules and organelles. This is the first report of the characterisation of haemocytes of the mud crab.
Impact of lobster size on catches and prediction of commercial spiny lobster landings in Brazil
Authors: Cruz Raúl , Silva Katia C. A. , Neves Soraya D. S. , Cintra Israel H. A.
Published: October 2013

On the Brazilian continental shelf, red spiny lobsters, Panulirus argus (Latreille, 1804) constitute a separate population with two distinct stocks, one in shallow waters (<50 m) and one in deeper waters (50-100 m). Stocks are highly exploited, especially undersized animals (≤75 mm CL) and older individuals. The observed decline in spiny lobster landings over the past two decades is believed to be due to overfishing in shallow waters, since over half the harvested lobsters are below the minimum legal size (75 mm CL), with a length at first capture of 61 mm CL. Spawning lobsters in deeper waters measure 96 mm CL at first capture; this coincides with the size class (90-99 mm CL) with the greatest reproductive potential. Furthermore, the capture of berried females and older lobsters (>135 mm CL) from deeper waters increases the risk of low recruitment and fishing collapse. The observed change in fishing patterns appears to be the consequence of increased fishing mortality (F) among pre-recruits. This is possibly the main cause of the large fluctuations observed in landings, although other factors, such as the interplay between environmental conditions and recruitment abundance, may have to be considered. Our results show that increasing the minimum legal size of red lobsters is likely to improve total landings in the long term, provided appropriate and tightly enforced control measures are designed and implemented.
Antisense-based RNA therapy of factor V deficiency: in vitro and ex vivo rescue of a F5 deep-intronic splicing mutation
Authors: Nuzzo Francesca , Radu Claudia , Baralle Marco , Spiezia Luca , Hackeng Tilman M. , Simioni Paolo , Castoldi Elisabetta
Published: October 2013

Key Points

Homozygosity for the F5 c.1296+268A>G splicing mutation causes life-threatening factor V deficiency. Mutation-specific antisense molecules can correct this splicing defect and restore factor V synthesis in the patient’s megakaryocytes.
Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program
Authors: Ladetto Marco , Lobetti-Bodoni Chiara , Mantoan Barbara , Ceccarelli Manuela , Boccomini Carola , Genuardi Elisa , Chiappella Annalisa , Baldini Luca , Rossi Giuseppe , Pulsoni Alessandro , Di Raimondo Francesco , Rigacci Luigi , Pinto Antonello , Galimberti Sara , Bari Alessia , Rota-Scalabrini Delia , Ferrari Angela , Zaja Francesco , Gallamini Andrea , Specchia Giorgina , Musto Pellegrino , Rossi Francesca Gaia , Gamba Enrica , Evangelista Andrea , Vitolo Umberto
Published: October 2013

Key Points

PCR negativity is a strong outcome predictor after rituximab-intensive immunochemotherapy at multiple posttreatment times. PCR is predictive even when maintenance is delivered, and accumulation of PCR-negative results further reduces the likelihood of relapse.
Development of SNP markers for genes of the phenylpropanoid pathway and their association to kernel and malting traits in barley
Authors: Peukert Manuela , Weise Stephan , Röder Marion S , Matthies Inge E
Published: October 2013

Background

Flavonoids are an important class of secondary compounds in angiosperms. Next to certain biological functions in plants, they play a role in the brewing process and have an effect on taste, color and aroma of beer. The aim of this study was to reveal the haplotype diversity of candidate genes involved in the phenylpropanoid biosynthesis pathway in cultivated barley varieties (Hordeum vulgare L.) and to determine associations to kernel and malting quality parameters.

Results

Five genes encoding phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), chalcone synthase (CHS), flavanone 3-hydroxylase (F3H) and dihydroflavonol reductase (DFR) of the phenylpropanoid biosynthesis pathway were partially resequenced in 16 diverse barley reference genotypes. Their localization in the barley genome, their genetic structure, and their genetic variation e.g. single nucleotide polymorphism (SNP) and Insertion/Deletion (InDel) patterns were revealed. In total, 130 SNPs and seven InDels were detected. Of these, 21 polymorphisms were converted into high-throughput pyrosequencing markers. The resulting SNP and haplotype patterns were used to calculate associations with kernel and malting quality parameters.

Conclusions

SNP patterns were found to be highly variable for the investigated genes. The developed high-throughput markers are applicable for assessing the genetic variability and for the determination of haplotype patterns in a set of barley accessions. The candidate genes PAL, C4H and F3H were shown to be associated to several malting properties like glassiness (PAL), viscosity (C4H) or to final attenuation (F3H).
Bolbase: a comprehensive genomics database for Brassica oleracea
Authors: Yu Jingyin , Zhao Meixia , Wang Xiaowu , Tong Chaobo , Huang Shunmou , Tehrim Sadia , Liu Yumei , Hua Wei , Liu Shengyi
Published: October 2013

Background

Brassica oleracea is a morphologically diverse species in the family Brassicaceae and contains a group of nutrition-rich vegetable crops, including common heading cabbage, cauliflower, broccoli, kohlrabi, kale, Brussels sprouts. This diversity along with its phylogenetic membership in a group of three diploid and three tetraploid species, and the recent availability of genome sequences within Brassica provide an unprecedented opportunity to study intra- and inter-species divergence and evolution in this species and its close relatives.

Description

We have developed a comprehensive database, Bolbase, which provides access to the B. oleracea genome data and comparative genomics information. The whole genome of B. oleracea is available, including nine fully assembled chromosomes and 1,848 scaffolds, with 45,758 predicted genes, 13,382 transposable elements, and 3,581 non-coding RNAs. Comparative genomics information is available, including syntenic regions among B. oleracea, Brassica rapa and Arabidopsis thaliana, synonymous (Ks) and non-synonymous (Ka) substitution rates between orthologous gene pairs, gene families or clusters, and differences in quantity, category, and distribution of transposable elements on chromosomes. Bolbase provides useful search and data mining tools, including a keyword search, a local BLAST server, and a customized GBrowse tool, which can be used to extract annotations of genome components, identify similar sequences and visualize syntenic regions among species. Users can download all genomic data and explore comparative genomics in a highly visual setting.

Conclusions

Bolbase is the first resource platform for the B. oleracea genome and for genomic comparisons with its relatives, and thus it will help the research community to better study the function and evolution of Brassica genomes as well as enhance molecular breeding research. This database will be updated regularly with new features, improvements to genome annotation, and new genomic sequences as they become available. Bolbase is freely available at http://ocri-genomics.org/bolbase.
The shaping and functional consequences of the dosage effect landscape in multiple myeloma
Authors: Samur Mehmet K , Shah Parantu K , Wang Xujun , Minvielle Stéphane , Magrangeas Florence , Avet-Loiseau Hervé , Munshi Nikhil C , Li Cheng
Published: October 2013

Background

Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs.

Results

We proposegene-wise dosage effect scoreandgenome-wide karyotype plotas tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers.

Conclusions

Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver genes in cancer genomics studies. The accompanying R code is available athttp://www.canevolve.org/dosageEffect/.
Retrospective analysis of antimicrobial resistance and bacterial spectrum of infection in Gabon, Central Africa
Authors: Alabi Abraham S , Frielinghaus Lisa , Kaba Harry , Kösters Katrin , Huson Michaëla A M , Kahl Barbara C , Peters Georg , Grobusch Martin P , Issifou Saadou , Kremsner Peter G , Schaumburg Frieder
Published: October 2013

Background

Physicians depend on reliable information on the local epidemiology of infection and antibiotic resistance rates to guide empiric treatment in critically ill patients. As these data are scarce for Central Africa, we performed a retrospective analysis of microbiological findings from a secondary care hospital in Gabon.

Methods

Microbiological reports from 2009 to 2012 were used to assess the non-susceptibility rates of the three most common isolates from six major types of infections (bloodstream, ear-eye-nose-throat, surgical site, skin and soft tissue, urinary tract and wound infection).

Results

A high diversity of pathogens was found, but Staphylococcus aureus was predominant in the majority of infections. Overall, the three most prevalent pathogens in children were S. aureus (33.7%), Streptococcus pyogenes (8.1%) and Escherichia coli (4.5%) and in adults S. aureus (23.5%), E. coli (15.1%) and Klebsiella pneumoniae (7.4%). In total, 5.8% (n = 19) of all S. aureus isolates were methicillin resistant. The proportion of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae was 15.4% (n = 78), 49.4% of all K. pneumoniae were ESBL-producer (n = 42).

Conclusion

The high diversity of potential pathogens and high resistance rates in Gram-negative bacteria challenge a rational empiric use of antibiotics. Countrywide continuous sentinel surveillance is therefore urgently needed.
Effect of an educational intervention on HPV knowledge and vaccine attitudes among urban employed women and female undergraduate students in China: a cross-sectional study
Authors: Chang Irene J , Huang Rong , He Wei , Zhang Shao-Kai , Wang Shao-Ming , Zhao Fang-Hui , Smith Jennifer S , Qiao You-Lin
Published: October 2013

Background

Due to the potential of human papillomavirus (HPV) vaccination for decreasing cervical cancer rates in Mainland China, where some of the highest incidences in the world have been reported, our study aimed to assess HPV and HPV vaccine knowledge, and to evaluate the effect of a brief educational intervention on HPV knowledge and vaccine acceptability in Chinese undergraduate students and employed women.

Methods

This multi-center, cross-sectional study was conducted across five representative cities of the five main geographical regions of Mainland China. Participants were selected from one comprehensive university and three to four companies in each city for a total of six comprehensive universities and 16 companies. A 62-item questionnaire on HPV knowledge and HPV vaccine acceptability was administered to participants before and after an educational intervention. The intervention consisted of an informative group lecture.

Results

A total of 1146 employed women and 557 female undergraduate students were surveyed between August and November 2011. Baseline HPV knowledge was low among both groups— 320/1146 (28%) of employed women and 66/557 (12%) of students had heard of HPV, while only 237/1146 (21%) of employed women and 40/557 (7.2%) of students knew that HPV is related to cervical cancer. After educational instruction, 947/1061 (89%) of employed women and 193/325 (59%) of students knew the relationship between HPV and cervical cancer (χ2 = 1041.8, p < 0.001 and χ2 = 278.5, p < 0.001, respectively). Post-intervention, vaccine acceptability increased from 881/1146 (77%) to 953/1061 (90%), (p = <0.001) in employed women and 405/557 (73%) in students to 266/325 (82%), (p < 0.001). Women in both groups cited concerns about the HPV vaccine’s safety, efficacy, and limited use to date as reasons for being unwilling to receive vaccination. 502/1146 (44%) of women were willing to vaccinate their children at baseline, which increased to 857/1061 (81%) post-intervention, p < 0.001.

Conclusions

Incorporation of our lecture-based education initiative into a government-sponsored or school-based program may improve HPV-related knowledge and HPV vaccine acceptability. Further studies are needed to evaluate and standardize HPV education programs in China.
Moxibustion in the management of irritable bowel syndrome: systematic review and meta-analysis
Authors: Park Jae-Woo , Lee Byung-Hee , Lee Hyangsook
Published: October 2013

Background

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Many patients suffer from IBS that can be difficult to treat, thus complementary therapies which may be effective and have a lower likelihood of adverse effects are being sought.

This systematic review and meta-analysis aimed at critically evaluating the current evidence on moxibustion for improving global symptoms of IBS.

Methods

We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, AMED, CINAHL, and CNKI databases for randomised controlled trials (RCTs) of moxibustion comparing with sham moxibustion, pharmacological medications, and other active treatments in patients with IBS. Trials should report global symptom improvement as an outcome measure. Risk of bias for each RCT was assessed according to criteria by the Cochrane Collaboration, and the dichotomous data were pooled according to the control intervention to obtain a risk ratio (RR) of global symptom improvement after moxibustion, with 95% confidence intervals (CI).

Results

A total of 20 RCTs were eligible for inclusion (n = 1625). The risk of bias was generally high. Compared with pharmacological medications, moxibustion significantly alleviated overall IBS symptoms but there was a moderate inconsistency among studies (7 RCTs, RR 1.33, 95% CI [1.15, 1.55], I2 = 46%). Moxibustion combined with acupuncture was more effective than pharmacological therapy but a moderate inconsistency among studies was found (4 RCTs, RR 1.24, 95% CI [1.09, 1.41], I2 = 36%). When moxibustion was added to pharmacological medications or herbal medicine, no additive benefit of moxibustion was shown compared with pharmacological medications or herbal medicine alone. One small sham-controlled trial found no difference between moxibustion and sham control in symptom severity (mean difference 0.35, 95% CI [−0.77, 1.47]). Moxibustion appears to be associated with few adverse events but the evidence is limited due to poor reporting.

Conclusions

This systematic review and meta-analysis suggests that moxibustion may provide benefit to IBS patients although the risk of bias in the included studies is relatively high. Future studies are necessary to confirm whether this finding is reproducible in carefully-designed and conducted trials and to firmly establish the place of moxibustion in current practice.
Cytotoxicity of Elaoephorbia drupifera and other Cameroonian medicinal plants against drug sensitive and multidrug resistant cancer cells
Authors: Kuete Victor , Voukeng Igor K , Tsobou Roger , Mbaveng Armelle T , Wiench Benjamin , Beng Veronique P , Efferth Thomas
Published: October 2013

Background

Multidrug resistance (MDR) is a major hurdle for cancer treatment worldwide and accounts for chemotherapy failure in over 90% of patients with metastatic cancer. Evidence of the cytotoxicity of Cameroonian plants against cancer cell lines including MDR phenotypes is been intensively and progressively provided. The present work was therefore designed to evaluate the cytotoxicity of the methanol extracts of twenty-two Cameroonian medicinal plants against sensitive and MDR cancer cell lines.

Methods

The methanol maceration was used to obtain the crude plant extracts whilst the cytotoxicity of the studied extracts was determined using a resazurin reduction assay.

Results

A preliminary assay on leukemia CCRF-CEM cells at 40 μg/mL shows that six of the twenty plant extract were able to enhance less than 50% of the growth proliferation of CCRF-CEM cells. These include Crinum zeylanicum (32.22%), Entada abyssinica (34.67%), Elaoephorbia drupifera (35.05%), Dioscorea bulbifera (45.88%), Eremomastax speciosa (46.07%) and Polistigma thonningii (45.11%). Among these six plants, E. drupifera showed the best activity with IC50 values below or around 30 μg/mL against the nine tested cancer cell lines. The lowest IC50 value of 8.40 μg/mL was recorded with the extract of E. drupifera against MDA-MB231 breast cancer cell line. The IC50 values below 10 μg/mL were recorded with the extracts of E. drupifera against MDA-MB231 breast cancer cells, C. zeylanicum against HCT116 p53+/+ and HCT116p53-/- colon cancer cells and E. abyssinica against HCT116 p53+/+ cells.

Conclusion

The results of the present study provide evidence of the cytotoxic potential of some Cameroonian medicinal plants and a baseline information for the potential use of Elaoephorbia drupifera in the treatment of sensitive and drug-resistant cancer cell lines.
Following the money: copy-paste of lifestyle counseling documentation and provider billing
Authors: Zhang Mary , Shubina Maria , Morrison Fritha , Turchin Alexander
Published: October 2013

Background

Evidence suggests that copy-pasted components of electronic notes may not reliably reflect the care delivered. Federal agencies have raised concerns that such components may be used to justify inappropriately inflated claims for reimbursement. It is not known whether copied information is used to justify higher evaluation and management (E&M) charges.

Methods

This retrospective cohort study aimed to assess the relationship between the level of evaluation and management (E&M) charges and the method of documentation (none, distinct or copied) of lifestyle counseling (diet, exercise and weight loss) for patients with diabetes mellitus. To determine the association, an ordered multinomial logistic regression model that corrected for clustering within individual providers and patients and adjusted for patient and encounter characteristics was utilized. E&M charge level served as the primary outcome variable. Patients were included if they were followed by primary care physicians affiliated with two academic hospitals for a minimum of two years between 01/01/2000 and 12/13/2009.

Results

Lifestyle counseling was documented in 65.4% of 155,168 primary care encounters of 16,164 patients. Copied counseling was identified in 12,527 encounters. In multivariable analysis higher E&M charges were associated with older patient age, longer notes, treatment with insulin, medication changes and acute complaints. However, copied lifestyle counseling was associated with a decrease of 70.5% in the odds of higher E&M charge levels when time spent on counseling (required to justify higher charges based on counseling) was recorded (p<0.0001). This finding is opposite to what would have been expected if the impetus for copied documentation of lifestyle counseling was an increase in submitted E&M charges.

Conclusion

There is no evidence that copied documentation of lifestyle counseling is used to justify higher evaluation and management charges. Higher charges were generally associated with indicators of complexity of care.
Usefulness of metabolic syndrome score in the prediction of angiographic coronary artery disease severity according to the presence of diabetes mellitus: relation with inflammatory markers and adipokines
Authors: Kim Jong-Youn , Choi Eui-Young , Mun Hee-Sun , Min Pil-Ki , Yoon Young-Won , Lee Byoung Kwon , Hong Bum-Kee , Rim Se-Joong , Kwon Hyuck Moon
Published: October 2013

Background

It is a matter of debate whether metabolic syndrome (MS) improves cardiovascular risk prediction beyond the risk associated with its individual components. The present study examined the association of MS score with high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), resistin, adiponectin, and angiographic coronary artery disease (CAD) severity according to the presence of DM. In addition, the predictive value of various clinical and biochemical parameters were analyzed, including the MS score for angiographic CAD.

Methods

The study enrolled 363 consecutive patients (196 men, 62 ± 11 years of age) who underwent coronary angiography for evaluation of chest pain. Blood samples were taken prior to elective coronary angiography. MS was defined by the National Cholesterol Education Program criteria, with MS score defined as the numbers of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD severity was assessed using the Gensini score.

Results

Of the 363 patients studied, 174 (48%) had CAD and 178 (49%) were diagnosed with MS. When the patients were divided into 4 subgroups according to MS score (0–1, 2, 3, 4–5), IL-6 levels and the CAD severity as assessed by the Gensini score increased as MS scores increased. In contrast, adiponectin levels decreased significantly as MS scores increased. When subjects were divided into two groups according to the presence of DM, the relationships between MS score and IL-6, adiponectin, and Gensini score were maintained only in patients without DM. Age, smoking, DM, MS score, and adiponectin independently predicted angiographic CAD in the whole population. However, age is the only predictor for angiographic CAD in patients with DM.

Conclusions

In the presence of DM, neither adipokines nor MS score predicted angiographic CAD. However, in non-diabetic patients, IL-6 and adiponectin showed progressive changes according to MS score, and MS score was an independent predictor of CAD in patients without DM.
Pituitary apoplexy induced by Gonadotropin-releasing hormone agonists for treating prostate cancer-report of first Asian case
Authors: Huang Tsung-Yi , Lin Jih-Pin , Lieu Ann-Shung , Chen Yi-Ting , Chen Hung-Sheng , Jang Mei-Yu , Shen Jung-Tsung , Wu Wen-Jeng , Huang Shu-Pin , Juan Yung-Shun
Published: October 2013

We present the first Asian case of a 77-year-old man who developed pituitary apoplexy (PA) soon after gonadotropin-releasing hormone agonist (GnRHa) (leuprorelin) injection to treat prostate cancer. Headache, ophthalmoplegia, visual field deficit, nausea, and vomiting are the typical characteristics of pituitary apoplexy. Though the occurrence rate is rare, the consequence of this condition can vary from mild symptoms such as headache to life-threatening scenarios like conscious change. Magnetic resonance imaging is the best imaging modality to detect PA and sublabial trans-sphenoid pituitary tumor removal can resolve most of PA symptoms and is so far the best solution in consensus. We also review 11 previous reported cases receiving GnRHa for androgen deprivation therapy of prostate cancer, and hope to alert clinicians to use GnRHa with caution.
Saturable human neopterin response to interferon-α assessed by a pharmacokinetic-pharmacodynamic model
Authors: Jeon Sangil , Juhn Jae-Hyeon , Han Seunghoon , Lee Jongtae , Hong Taegon , Paek Jeongki , Yim Dong-Seok
Published: October 2013

Background

In this study, we developed a pharmacokinetic (PK)- pharmacodynamic (PD) model of a new sustained release formulation of interferon-α-2a (SR-IFN-α) using the blood concentration of IFN-α and neopterin in order to quantify the magnitude and saturation of neopterin production over time in healthy volunteers. The SR-IFN-α in this study is a solid microparticular formulation manufactured by spray drying of a feeding solution containing IFN-α, a biocompatible polymer (polyethylene glycol) and sodium hyaluronate.

Methods

The full PK and PD (neopterin concentration) datasets from 24 healthy subjects obtained after single doses of 9, 18, 27 and 36 MIU of subcutaneous SR-IFN-α were used to build the mixed-effect model using NONMEM (version 7.2) with the GFORTRAN compiler.

Results

A one-compartment model with first-order elimination and a mixture of zero- and first-order absorption was chosen to describe the PK of SR-IFN-α. The time-concentration profile of neopterin, the PD marker, was described by a turnover model combined with a single transit compartment. The saturable pattern of the neopterin response blurring the dose–response relationship of SR-IFN-α was addressed by introducing the concept of the EC50 increasing over time.

Conclusions

The PK-PD model of SR-IFN-α developed in this study has presented a quantitative tool to assess the time-course of a saturable neopterin response in humans.
Novel solutions for side information generation and fusion in multiview DVC
Authors: Petrazzuoli Giovanni , Cagnazzo Marco , Pesquet-Popescu Béatrice
Published: October 2013

One of the key problems in distributed video coding is the generation of side information. This task consists of producing an estimate of an image with some neighboring ones, such as those taken by the same camera at different time instants, or, in the case of multiview setups, images taken at the same time instant by different cameras. If both estimates are available, a further problem arises, which is how to merge them in order to create a single side information. This problem is very relevant since a good estimate of the unknown image will require only a few bits to be corrected. Considering a multiview distributed video-coding setup, we propose a novel technique for inter-view interpolation based on occlusion prediction, a new fusion technique from multiple estimates, and finally an adaptive validation step for switching among the three possible side information images: temporal, inter-view, and fusion. We provide a comprehensive set of experimental results, which indicate bit rate reductions of more than 9% in average; moreover, we observe much more consistent results with respect to state-of-the-art techniques.
A comprehensive map of the influenza A virus replication cycle
Authors: Matsuoka Yukiko , Matsumae Hiromi , Katoh Manami , Eisfeld Amie J , Neumann Gabriele , Hase Takeshi , Ghosh Samik , Shoemaker Jason E , Lopes Tiago JS , Watanabe Tokiko , Watanabe Shinji , Fukuyama Satoshi , Kitano Hiroaki , Kawaoka Yoshihiro
Published: October 2013

Background

Influenza is a common infectious disease caused by influenza viruses. Annual epidemics cause severe illnesses, deaths, and economic loss around the world. To better defend against influenza viral infection, it is essential to understand its mechanisms and associated host responses. Many studies have been conducted to elucidate these mechanisms, however, the overall picture remains incompletely understood. A systematic understanding of influenza viral infection in host cells is needed to facilitate the identification of influential host response mechanisms and potential drug targets.

Description

We constructed a comprehensive map of the influenza A virus (‘IAV’) life cycle (‘FluMap’) by undertaking a literature-based, manual curation approach. Based on information obtained from publicly available pathway databases, updated with literature-based information and input from expert virologists and immunologists, FluMap is currently composed of 960 factors (i.e., proteins, mRNAs etc.) and 456 reactions, and is annotated with ~500 papers and curation comments. In addition to detailing the type of molecular interactions, isolate/strain specific data are also available. The FluMap was built with the pathway editor CellDesigner in standard SBML (Systems Biology Markup Language) format and visualized as an SBGN (Systems Biology Graphical Notation) diagram. It is also available as a web service (online map) based on the iPathways+ system to enable community discussion by influenza researchers. We also demonstrate computational network analyses to identify targets using the FluMap.

Conclusion

The FluMap is a comprehensive pathway map that can serve as a graphically presented knowledge-base and as a platform to analyze functional interactions between IAV and host factors. Publicly available webtools will allow continuous updating to ensure the most reliable representation of the host-virus interaction network. The FluMap is available athttp://www.influenza-x.org/flumap/.
Non-neoplastic bulky mediastinal mass presentation in an adolescent patient: a case report
Authors: Blatyta Paula Fraiman , Borba Claudio Carneiro , de Queiroz Ligia Reis , de Medeiros Raphael Salles Scortegagna , de Campos Fabiana Gomes , Bendit Israel
Published: October 2013

Introduction

Mediastinal masses in pediatric patients are very heterogeneous in origin and etiology. In the first decade of life, 70% of the mediastinal masses are benign whereas malignant tumors are more frequent in the second decade of life. Among the mediastinal masses, lymph nodes are the most common involved structures and could be enlarged due to a lymphoma, leukemia, metastatic disease, or due to infectious diseases as sarcoidosis, tuberculosis and others.

Case presentation

We report a case of a 13-year-old Caucasian girl who came to the emergency room with a history of intermittent fever, weight loss and night sweating for at least 1 month. A radiologic image work-up presented an anterior and posterior mediastinal mass. The 18F-fluorodeoxyglucose positron emission tomography presented a high maximum standard uptake value, which directed our decision for mediastinal biopsy for diagnostic elucidation. Histologic examination described the mass as granulomatous tuberculosis. The patient was treated with anti-tuberculosis therapy and developed a full clinical recovery.

Conclusions

The present case report demonstrates that a bulky mediastinal lymphadenopathy detected on 18F-fluorodeoxyglucose positron emission tomography is not always a malignant lesion, and in countries where tuberculosis is endemic, this etiology should not be forgotten during clinical investigations. There is a need for more accurate cut-off values for this technology; meanwhile, the further investigation of patients with bulky mediastinal masses with procedures such as the open biopsy is indispensable.
Selection and validation of reference genes for gene expression analysis in apomictic and sexual Cenchrus ciliaris
Authors: Simon Bindu , Conner Joann A , Ozias-Akins Peggy
Published: October 2013

Background

Apomixis is a naturally occurring asexual mode of seed reproduction resulting in offspring genetically identical to the maternal plant. Identifying differential gene expression patterns between apomictic and sexual plants is valuable to help deconstruct the trait. Quantitative RT-PCR (qRT-PCR) is a popular method for analyzing gene expression. Normalizing gene expression data using proper reference genes which show stable expression under investigated conditions is critical in qRT-PCR analysis. We used qRT-PCR to validate expression and stability of six potential reference genes (EF1alpha, EIF4A, UBCE, GAPDH, ACT2 and TUBA) in vegetative and reproductive tissues of B-2S and B-12-9 accessions of C. ciliaris.

Findings

Among tissue types evaluated, EF1alpha showed the highest level of expression while TUBA showed the lowest. When all tissue types were evaluated and compared between genotypes, EIF4A was the most stable reference gene. Gene expression stability for specific ovary stages of B-2S and B-12-9 was also determined. Except for TUBA, all other tested reference genes could be used for any stage-specific ovary tissue normalization, irrespective of the mode of reproduction.

Conclusion

Our gene expression stability assay using six reference genes, in sexual and apomictic accessions of C. ciliaris, suggests that EIF4A is the most stable gene across all tissue types analyzed. All other tested reference genes, with the exception of TUBA, could be used for gene expression comparison studies between sexual and apomictic ovaries over multiple developmental stages. This reference gene validation data in C. ciliaris will serve as an important base for future apomixis-related transcriptome data validation.
Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech
Authors: Worthey Elizabeth A , Raca Gordana , Laffin Jennifer J , Wilk Brandon M , Harris Jeremy M , Jakielski Kathy J , Dimmock David P , Strand Edythe A , Shriberg Lawrence D
Published: October 2013

Background

Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation inFOXP2in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS.

Methods

As part of a larger study of children and youth with motor speech sound disorders, 32 participants were classified as positive for CAS on the basis of a behavioral classification marker using auditory-perceptual and acoustic methods that quantify the competence, precision and stability of a speaker’s speech, prosody and voice. WES of 10 randomly selected participants was completed using the Illumina Genome Analyzer IIx Sequencing System. Image analysis, base calling, demultiplexing, read mapping, and variant calling were performed using Illumina software. Software developed in-house was used for variant annotation, prioritization and interpretation to identify those variants likely to be deleterious to neurodevelopmental substrates of speech-language development.

Results

Among potentially deleterious variants, clinically reportable findings of interest occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which included six genes either strongly associated with CAS (FOXP1andCNTNAP2) or associated with disorders with phenotypes overlapping CAS (ATP13A4,CNTNAP1,KIAA0319andSETX). A total of 8 (80%) of the 10 participants had clinically reportable variants in one or two of the six genes, with variants inATP13A4,KIAA0319andCNTNAP2being the most prevalent.

Conclusions

Similar to the results reported in emerging WES studies of other complex neurodevelopmental disorders, our findings from this first WES study of CAS are interpreted as support for heterogeneous genetic origins of this pediatric motor speech disorder with multiple genes, pathways and complex interactions. We also submit that our findings illustrate the potential use of WES for both gene identification and case-by-case clinical diagnostics in pediatric motor speech disorders.