bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between dopamine and renalase in type 2 diabetic patients with and without diabetic nephropathy
Authors: Gaber Eman W , El-Attar Hoda A
Published: May 2013

Background:

Diabetes clustered with hypertension and nephropathy is the commonest cause of end stage renal disease. Dopamine, an ancestral catecholamine, is involved in the regulation of sodium homeostasis and blood pressure. Renalase metabolises circulating catecholamines and is thought to regulate blood pressure. This study aimed to assess the relationship between dopamine and renalase in type 2 diabetic patients with and without diabetic nephropathy.

Methods:

This study was conducted on 80 subjects. Group 1 included 10 healthy subjects as controls, group 2 included 60 type 2 diabetic patients with normal or increased albumin excretion rate (AER) and group 3 included 10 type 2 diabetic patients on maintenance hemodialysis (HD). Thorough clinical assessment and laboratory investigations included estimation of serum levels of fasting glucose (FSG), creatinine, urea, calcium, phosphorus, cholesterol (total and high and low-density lipoprotein) and triglycerides. Urinary albumin/creatinine ratio (ACR) was estimated to assess AER and plasma dopamine and serum renalase were estimated.

Results:

There were no significant differences in the mean dopamine levels between the three studied groups. Renalase level was significantly higher in HD patients than controls and other diabetic patients. Diabetic patients with increased AER had significantly higher systolic blood pressure, serum creatinine and renalase levels than diabetic patients with normal AER. Diabetic patients with increased serum creatinine ≥ 1.5 mg/dl had significantly longer duration of diabetes and higher systolic and diastolic blood pressures. They also had significantly higher AER, FSG, dopamine and renalase levels than diabetic patients with serum creatinine < 1.5 mg/dl. ACR was positively correlated with duration of diabetes, systolic and diastolic blood pressure and serum creatinine and negatively correlated with the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Renalase was positively correlated with diastolic blood pressure, ACR, serum creatinine, phosphorus and dopamine

Conclusion:

Serum levels of renalase are increased in type 2 diabetic patients with renal dysfunction. Renalase levels may be increased to compensate for the increase in dopamine level. The higher renalase level in HD patients may be due to much lower renalase clearance, higher production or slower degradation in these patients.
Comparison of 12-W Versus 14-W Endovenous Laser Ablation in the Treatment of Great Saphenous Varicose Veins
Authors: Samuel Nehemiah , Wallace Tom , Carradice Daniel , Mazari Fayyaz AK , Chetter Ian C.
Published: May 2013

Introduction:

Endovenous laser ablation (EVLA) has been demonstrated to be an effective treatment for lower limb varicose veins in the short and midterm results. This study reports the 5-year outcomes of EVLA technique at different power settings.

Methods:

Patients with primary symptomatic, unilateral varicose veins secondary to saphenofemoral junction (SFJ) incompetence and great saphenous vein (GSV) reflux were recruited and randomized to either 12W (intermittent laser withdrawal) or 14W (continuous laser withdrawal). They were assessed at baseline, 1, 6, 12, 52, 104 weeks, and 5 years. Outcome measures included: Venous Clinical Severity Score (VCSS), pain scores, time taken to return to normal functions, complications, recurrence, quality of life (QoL), and duplex ultrasound findings.

Results:

76 consecutive patients, M: F 30:46, median age 54(IQR: 37.3-59) years were randomized.

Intragroup analysis:

Significant improvement was seen in both groups in VCSS, pain scores, Aberdeen varicose vein questionnaire (AVVQ) scores, Shortform-36 (SF-36) and Euroqol (EQ-5D) domains over the follow-up period ( P < 0.05).

Intergroup analysis:

Over 5 years, clinically recurrent varicosities and duplex detected SFJ incompetence was less frequent and patient satisfaction with cosmetic outcome significantly higher in the 14W group ( P < 0.05). There was no significant difference between the groups in duration of procedure, postoperative pain scores, return to normal functioning, complications, VCSS, disease specific (AVVQ) and generic (SF36, EQ-5D) QoL measures ( P > 0.05).

Conclusion:

Late outcomes following EVLA were superior for the 14W continuous power settings achieving better long term venous occlusion and lowered recurrence rates without increasing post-operative morbidity. Hence 14W continuous setting should be the energy delivery mode of choice.
The Great White Hope? Examining the White Privilege and Epistemology of an Urban High School Principal
Authors: Green Terrance L. , Dantley Michael E.
Published: May 2013

This case was developed for use in courses on the principalship as well as school reform, with an emphasis on developing socially just, epistemologically and racially conscious school leaders. Data are presented about the principal, the school district, the school, the students, and the community. This case explores notions of White privilege to develop epistemological and racial consciousnesses, and works toward disrupting systems of repression. To do so, this case seeks to problematize how urban school reform can be self-serving for White principals, and aims to provoke urban school principals to go beyond epistemological and racial awareness, to action. Course instructors can use this case to examine students’ epistemologies as well as racial consciousness, explore the nexus of White privilege and urban school reform, and discuss race and racism in American schools.
The impact of material selection on arrow design and optimal selection for competition
Authors: Park James L
Published: May 2013

Modern arrow shafts are usually tubular and are constructed using high-strength materials, with most competition arrows now using carbon fibre composites. The need to mount the arrow components (and in particular the arrow point) internally and the need to retain sufficient wall strength to avoid crushing combine to set design limits on the arrow’s mass–diameter relationship for a given arrow shaft material. This article considers those design limits and the consequent selection of the optimal arrow shafts to use for the various types of major archery competitions, depending upon the major score-detracting factors. It is shown that for a given arrow shaft material, a simple set of rules can be used for the selection.
Small School Reform
Authors: Bronson Carroll E.
Published: May 2013

This qualitative ethnographic case study explored the evolution of a public urban high school in its 3rd year of small school reform. The study focused on how the high school proceeded from its initial concept, moving to a small school program, and emerging as a new small high school. Data collection included interviews, observations, and document review to develop a case study of one small high school sharing a multiplex building. The first key finding, “Too Many Pieces, Not Enough Glue,” revealed that the school had too many new programs starting at once and they lacked a clear understanding of their concept and vision for their new small school, training on the Montessori philosophies, teaching and learning in small schools, and how to operate within a teacher-cooperative model. The second key finding, “A Continuous Struggle,” revealed that the shared building space presented problems for teachers and students. District policies remain unchanged, resulting in staff and students resorting to activist approaches to get things done. These findings offer small school reform leaders suggestions for developing and sustaining a small school culture and cohesion despite the pressures to revert back to top-down, comprehensive high school norms.
Of Course I Don’t Post Too Much
Authors: Holmes Kristie
Published: May 2013

This study explored participant perception regarding the ease of relationship maintenance online, honesty in information sharing, and whether people were more, less, or similarly concerned about their online image over their in-person image given the prevalence and preference for electronic communication in most relationship forms. Most of the 296 participants were consistently honest in their online information sharing. Women were more likely to worry about maintaining their in-person image than men and found it easier to maintain friendships online. Participants aged 30 to 45 years were the least likely to post misleading information about themselves or their interests. Participants seemed to equate “post a lot” of information online as equated to “post too much” as not a single participant revealed that they “post a lot.”
Social Constructionism in the Context of Organization Development
Authors: Camargo-Borges Celiane , Rasera Emerson F.
Published: May 2013

The world faces rapid changes that call for new epistemologies and methodologies that can generate innovative forms of “being” and “doing” within organizations. This article investigates conceptual and practical resources from the social constructionist perspective that can be useful in realizing the transformation of organizations. Initially, a global context of the world in change is described, explaining the consequences for organizations; then social constructionism is introduced as a postmodern epistemology and offered as a potential approach to the organizational development field in supporting research and intervention. Some perspectives for action and knowledge production are offered in the context of an organization. Finally, some resources with examples will be articulated; these new frameworks for action can be effective for organizations coping in times of change.
Determinants of Gender Differences in Self-Rated Health Among Older Population
Authors: Singh Lucky , Arokiasamy Perianayagam , Singh Prashant Kumar , Rai Rajesh Kumar
Published: May 2013

The purpose of this study is to examine gender difference in self-rated health among older population in India. Data from the 60th round of National Sample Survey Organization on 34,831 older persons are used. The present study measured self-rated health categorized as “poor” and “good.” We used bivariate and binary logistic regression model to investigate differences and factors that best explain and predict the self-rated health among older persons. Results show that poor self-rated health was more common among women than men. Furthermore, the poor self-rated health was higher among Muslims, Scheduled Castes, and women residing in rural areas. Findings suggest a clear need for gender-sensitive health interventions.
AML1-ETO mediates hematopoietic self-renewal and leukemogenesis through a COX/β-catenin signaling pathway
Authors: Zhang Yiyun , Wang Jianfeng , Wheat Justin , Chen Xi , Jin Shan , Sadrzadeh Hossein , Fathi Amir T. , Peterson Randall T. , Kung Andrew L. , Sweetser David A. , Yeh Jing-Ruey Joanna
Published: May 2013

Key Points

AE induces hematopoietic self-renewal through a COX/prostaglandin E2/β-catenin signaling pathway. Clinically available COX inhibitors may target AML stem cells and suppress AML of various karyotypes.
Endemic Burkitt lymphoma is associated with strength and diversity of Plasmodium falciparum malaria stage-specific antigen antibody response
Authors: Aka Peter , Vila Maria Candida , Jariwala Amar , Nkrumah Francis , Emmanuel Benjamin , Yagi Masanori , Palacpac Nirianne Marie Q. , Periago Maria V. , Neequaye Janet , Kiruthu Christine , Tougan Takahiro , Levine Paul H. , Biggar Robert J. , Pfeiffer Ruth M. , Bhatia Kishor , Horii Toshihiro , Bethony Jeffrey M. , Mbulaiteye Sam M.
Published: May 2013

Key Points

eBL was positively associated with anti–HRP-II antibodies and inversely associated with anti-SE36 antibodies. Anti–HRP-II antibodies suggest that recent malaria infection triggers the onset of eBL; anti-SE36 antibodies suggest long-term infection and immunity.
Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation
Authors: De Filippo Katia , Dudeck Anne , Hasenberg Mike , Nye Emma , van Rooijen Nico , Hartmann Karin , Gunzer Matthias , Roers Axel , Hogg Nancy
Published: May 2013

Key Points

Mast cells contribute to early neutrophil recruitment. Mast cells and macrophages both make CXCL1 and CXCL2.
Long noncoding RNAs in biology and hematopoiesis
Authors: Paralkar Vikram R. , Weiss Mitchell J.
Published: May 2013

Genome and transcriptome sequencing have revealed a rich assortment of noncoding RNAs in eukaryote cells, including long noncoding RNAs (lncRNAs), which regulate gene expression independent of protein coding potential. LncRNAs modulate protein coding gene expression in many cell types by regulating multiple processes, including epigenetic control of transcription, mRNA stability, and protein localization. Although little is known about lncRNAs in hematopoiesis, they are likely to exert widespread roles in this process.
Exhaled volatile organic compounds predict exacerbations of childhood asthma in a 1-year prospective study
Authors: Robroeks Charlotte M. , van Berkel Joep J. , Jöbsis Quirijn , van Schooten Frederik-Jan , Dallinga Jan W. , Wouters Emiel F. , Dompeling Edward
Published: May 2013

The hypothesis was that prediction of asthma exacerbations in children is possible by profiles of exhaled volatile organic compounds (VOCs), a noninvasive measure of airway inflammation. The aims of the present study were to determine: 1) whether VOCs in exhaled breath are able to predict asthma exacerbations; and 2) the time course and chemical background of the most predictive VOCs.

A prospective study was performed in 40 children with asthma over 1 year. At standard 2-month intervals, exhaled nitric oxide fraction (FeNO), VOC profiles in exhaled breath samples, lung function and symptoms were determined in a standardised way. VOC profiles were analysed by gas chromatography–time-of-flight mass spectrometry.

16 out of 40 children experienced an exacerbation. With support vector machine analysis, the most optimal model of baseline measurementsversusexacerbation within patients was based on six VOCs (correct classification 96%, sensitivity 100% and specificity 93%). The model of baseline values of patients with compared to those without an exacerbation consisted of seven VOCs (correct classification 91%, sensitivity 79% and specificity 100%).FeNOand lung function were not predictive for exacerbations.

This study indicates that a combination of different exhaled VOCs is able to predict exacerbations of childhood asthma.
FAQs about the GOLD 2011 assessment proposal of COPD: a comparative analysis of four different cohorts
Authors: Agusti Alvar , Hurd Suzanne , Jones Paul , Fabbri Leonardo M. , Martinez Fernando , Vogelmeier Claus , Vestbo Jørgen , Rodriguez-Roisin Robert
Published: May 2013

Since the publication of the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposal for the assessment of chronic obstructive lung disease (COPD), four studies have used existing cohorts to explore the characteristics, temporal variability and/or relationship with outcomes of the four resulting patient categories (A, B, C and D).

Here, we compare their results and address a number of frequently asked questions (FAQs) on the topic.

The most salient findings were that: 1) the prevalence of these four groups depends on the specific population studied, C being the least prevalent; 2) comorbidities are particularly prevalent in the two “high-symptom” groups (B and D); 3) patients classifiedZ as A or D tend to remain in the same group over time, whereas those classified as B or C change substantially during follow-up; 4) mortality at 3 years was lowest in A and worst in D but surprisingly similar (and intermediate) in B and C; and 5) the incidence of exacerbations during follow-up increases progressively from A to D but that of hospitalisations behave similarly to mortality.

These results identify several strengths and shortcomings of the new GOLD assessment proposal, particularly that group B is associated with more morbidity and high mortality.
Paediatrics in Vienna
Authors: Midulla Fabio , Lombardi Enrico , Lødrup Carlsen Karin C. , Regamey Nicolas , Grigg Jonathan , Ross Russell Robert I. , Turner Steve W. , Priftis Kostas , Eber Ernst
Published: May 2013

The aim of this update is to describe, in the context of the current literature, major papers from the seven groups of the Paediatric Assembly (Respiratory Physiology; Asthma and Allergy; Cystic Fibrosis; Respiratory Infection and Immunology; Neonatology and Paediatric Intensive Care; Respiratory Epidemiology; and Bronchology) presented during the annual European Respiratory Society congress held in 2012 in Vienna, Austria.
Plasma advanced glycation end-products and skin autofluorescence are increased in COPD
Authors: Gopal Poornima , Reynaert Niki L. , Scheijen Jean L.J.M. , Engelen Lean , Schalkwijk Casper G. , Franssen Frits M.E. , Wouters Emiel F.M. , Rutten Erica P.A.
Published: May 2013

Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. These conditions may lead to the formation of advanced glycation end-products (AGEs).

In this study we investigated in 88 COPD patients and 55 control subjects (80% ex-smokers) the association of the plasma protein-bound AGEs Nϵ-(carboxymethyl)lysine (CML), pentosidine, Nϵ-(carboxyethyl)lysine (CEL), and AGE accumulation in skin by skin autofluorescence (AFR), with lung function.

Mean±sdplasma CML was decreased (COPD 61.6±15.6 nmol·mmol−1lysine, never-smokers 80.7±19.8 nmol·mmol−1lysine and ex-smokers 82.9±19.3 nmol·mmol−1lysine) and CEL (COPD 39.1±10.9 nmol·mmol−1lysine, never-smokers 30.4±5.0 nmol·mmol−1lysine and ex-smokers 27.7±6.4 nmol·mmol−1lysine) and AFR (COPD 3.33±0.67 arbitrary units (AU), never-smokers 2.24±0.45 AU and ex-smokers 2.31±0.47 AU) were increased in COPD patients compared to controls. Disease state was inversely associated with CML, and linearly associated with CEL and AFR. Performing regression analyses in the total group, CEL and AFR showed a negative association and CML a positive association with lung function, even after correction for potential confounders.

In conclusion, CEL and AFR were negatively and CML was positively associated with disease state. In the total group only the AGEs showed an association with forced expiratory volume in 1 s. Our data suggest that AGEs are involved in the pathophysiology of COPD, although their exact role remains to be determined.
Lung adenocarcinoma subtypes based on expression of human airway basal cell genes
Authors: Fukui Tomoya , Shaykhiev Renat , Agosto-Perez Francisco , Mezey Jason G. , Downey Robert J. , Travis William D. , Crystal Ronald G.
Published: May 2013

Lung cancer, including lung adenocarcinoma, is a heterogeneous disease, which evolves from molecular alterations in the airway epithelium. This study explores whether a subtype of lung adenocarcinomas expresses the unique molecular features of human airway basal cells (BCs), and how expression of the airway BC features correlates with the molecular, pathological and clinical phenotype of lung adenocarcinoma.

Three independent lung adenocarcinoma data sets were analysed for expression of genes that constitute the airway BC signature. Expression of the BC signature in lung adenocarcinoma was then correlated to clinical and biological parameters.

Remarkable enrichment of airway BC signature genes was found in lung adenocarcinomas. A subset of lung adenocarcinomas (BC-high adenocarcinoma) exhibited high expression of BC signature genes in association with poorer tumour grade, higher frequency of vascular invasion and shorter survival than adenocarcinomas with lower expression of these genes. At the molecular level, BC-high adenocarcinomas displayed a higher frequency ofKRASmutations, activation of transcriptional networks and pathways related to cell cycle, extracellular matrix organisation, and a distinct differentiation pattern with suppression of ciliated and exocrine bronchiolar cell (Clara cell)-related genes.

Activation of the airway BC programme is a molecular feature of a distinct, aggressive subtype of lung adenocarcinoma.
Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation
Authors: Hostettler Katrin E. , Halter Jörg P. , Gerull Sabine , Lardinois Didier , Savic Spasenija , Roth Michael , Tamm Michael
Published: May 2013

Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS).

Cells were isolated from surgical lung biopsies of eight HSCT patients with BOS. Proliferation was assessed by [3H]-thymidine incorporation.

Biopsies revealed constrictive bronchiolitis obliterans in three patients and lymphocytic bronchiolitis in five patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Costimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1of patients with bronchiolitis obliterans was unchanged.

Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMFin vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT.
Serum uric acid as a predictor of mortality and future exacerbations of COPD
Authors: Bartziokas Konstantinos , Papaioannou Andriana I. , Loukides Stelios , Papadopoulos Alexandros , Haniotou Aikaterini , Papiris Spyridon , Kostikas Konstantinos
Published: May 2013

Serum uric acid is increased in respiratory disease, especially in the presence of hypoxia and systemic inflammation. We evaluated serum uric acid as a biomarker for prediction of mortality and future acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Serum uric acid was measured in 314 eligible consecutive patients on admission for AECOPD. Patients were evaluated monthly for 1 year.

Uric acid levels were higher in patients with more severe airflow limitation and in those experiencing frequent exacerbations. High uric acid levels (≥6.9 mg·dL−1) were an independent predictor of 30-day mortality in multivariate Cox regression analysis (HR 1.317, 95% CI 1.011–1.736; p=0.044), but not of 1-year mortality. Patients with high serum uric acid required more prolonged hospitalisation, and more often needed noninvasive ventilation and admission to the intensive care unit within 30 days. In addition, high uric acid levels were associated with increased risk and hospitalisation for AECOPD in 1 year in multivariate Poisson regression analysis (incidence rate ratio 1.184 (95% CI 1.125–1.246) and 1.190 (95% CI 1.105–1.282), respectively; both p<0.001).

Serum uric acid is associated with increased 30-day mortality and risk for AECOPD and hospitalisations in 1-year follow-up. This low-cost biomarker may be useful in the identification of high-risk chronic obstructive pulmonary disease patients that could benefit from intensive management.
Proteomic analyses and identification of arginine methylated proteins differentially recognized by autosera from anti-Sm positive SLE patients
Authors: Chang Hong-How , Hu Huan-Hsuan , Lee Yu-Jen , Wei Hung-Ming , Fan-June Ming-Chun , Hsu Tsai-Ching , Tsay Gregory J , Li Chuan
Published: May 2013

Background

Antibodies against spliceosome Sm proteins (anti-Sm autoantibodies) are specific to the autoimmune disease systemic lupus erythematosus (SLE). Anti-Sm autosera have been reported to specifically recognize Sm D1 and D3 with symmetric di-methylarginines (sDMA). We investigated if anti-Sm sera from local SLE patients can differentially recognize Sm proteins or any other proteins due to their methylation states.

Results

We prepared HeLa cell proteins at normal or hypomethylation states (treated with an indirect methyltransferase inhibitor adenosine dialdehyde, AdOx). A few signals detected by the anti-Sm positive sera from typical SLE patients decreased consistently in the immunoblots of hypomethylated cell extracts. The differentially detected signals by one serum (Sm1) were pinpointed by two-dimensional electrophoresis and identified by mass spectrometry. Three identified proteins: splicing factor, proline- and glutamine-rich (SFPQ), heterogeneous nuclear ribonucleoprotein D-like (hnRNP DL) and cellular nucleic acid binding protein (CNBP) are known to contain methylarginines in their glycine and arginine rich (GAR) sequences. We showed that recombinant hnRNP DL and CNBP expressed in Escherichia coli can be detected by all anti-Sm positive sera we tested. As CNBP appeared to be differentially detected by the SLE sera in the pilot study, differential recognition of arginine methylated CNBP protein by the anti-Sm positive sera were further examined. Hypomethylated FLAG-CNBP protein immunopurified from AdOx-treated HeLa cells was less recognized by Sm1 compared to the CNBP protein expressed in untreated cells. Two of 20 other anti-Sm positive sera specifically differentiated the FLAG-CNBP protein expressed in HeLa cells due to the methylation. We also observed deferential recognition of methylated recombinant CNBP proteins expressed from E. coli by some of the autosera.

Conclusion

Our study showed that hnRNP DL and CNBP are novel antigens for SLE patients and the recognition of CNBP might be differentiated dependent on the level of arginine methylation.
Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis
Authors: Jenkins Victoria A , Barton Geraint R , Robertson Brian D , Williams Kerstin J
Published: May 2013

Background

Nitrogen is an essential element for bacterial growth and an important component of biological macromolecules. Consequently, responding to nitrogen limitation is critical for bacterial survival and involves the interplay of signalling pathways and transcriptional regulation of nitrogen assimilation and scavenging genes. In the soil dwelling saprophyte Mycobacterium smegmatis the OmpR-type response regulator GlnR is thought to mediate the transcriptomic response to nitrogen limitation. However, to date only ten genes have been shown to be in the GlnR regulon, a vastly reduced number compared to other organisms.

Results

We investigated the role of GlnR in the nitrogen limitation response and determined the entire GlnR regulon, by combining expression profiling of M. smegmatis wild type and glnR deletion mutant, with GlnR-specific chromatin immunoprecipitation and high throughput sequencing. We identify 53 GlnR binding sites during nitrogen limitation that control the expression of over 100 genes, demonstrating that GlnR is the regulator controlling the assimilation and utilisation of nitrogen. We also determine a consensus GlnR binding motif and identify key residues within the motif that are required for specific GlnR binding.

Conclusions

We have demonstrated that GlnR is the global nitrogen response regulator in M. smegmatis, directly regulating the expression of more than 100 genes. GlnR controls key nitrogen stress survival processes including primary nitrogen metabolism pathways, the ability to utilise nitrate and urea as alternative nitrogen sources, and the potential to use cellular components to provide a source of ammonium. These studies further our understanding of how mycobacteria survive nutrient limiting conditions.
Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs
Authors: Christoforides Alexis , Carpten John D , Weiss Glen J , Demeure Michael J , Von Hoff Daniel D , Craig David W
Published: May 2013

Background

The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations – changes specific to a tumor and not within an individual’s germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific.

Results

We have developed a generalized Bayesian analysis framework for matched tumor/normal samples with the purpose of identifying tumor-specific alterations such as single nucleotide mutations, small insertions/deletions, and structural variation. We describe our methodology, and discuss its application to other types of paired-tissue analysis such as the detection of loss of heterozygosity as well as allelic imbalance. We also demonstrate the high level of sensitivity and specificity in discovering simulated somatic mutations, for various combinations of a) genomic coverage and b) emulated heterogeneity.

Conclusion

We present a Java-based implementation of our methods named Seurat, which is made available for free academic use. We have demonstrated and reported on the discovery of different types of somatic change by applying Seurat to an experimentally-derived cancer dataset using our methods; and have discussed considerations and practices regarding the accurate detection of somatic events in cancer genomes. Seurat is available at https://sites.google.com/site/seuratsomatic.
Functional transcriptomic analysis of the role of MAB-5/Hox in Q neuroblast migration in Caenorhabditis elegans
Authors: Tamayo Joel V , Gujar Mahekta , Macdonald Stuart J , Lundquist Erik A
Published: May 2013

Background

Directed cell migration is a fundamental process in normal development and in tumor metastasis. In C. elegans the MAB-5/Hox transcription factor is a determinant of posterior migration of the Q neuroblast descendants. In this work, mab-5 transcriptional targets that control Q descendant migration are identified by comparing RNA-seq profiles in wild type and mab-5 mutant backgrounds.

Results

Transcriptome profiling is a widely-used and potent tool to identify genes involved in developmental and pathological processes, and is most informative when RNA can be isolated from individual cell or tissue types. Cell-specific RNA samples can be difficult to obtain from invertebrate model organisms such as Drosophila and C. elegans. Here we test the utility of combining a whole organism RNA-seq approach with mab-5 loss and gain-of-function mutants and functional validation using RNAi to identify genes regulated by MAB-5 to control Q descendant migration. We identified 22 genes whose expression was controlled by mab-5 and that controlled Q descendant migration. Genes regulated by mab-5 were enriched for secreted and transmembrane molecules involved in basement membrane interaction and modification, and some affected Q descendant migration.

Conclusions

Our results indicate that a whole-organism RNA-seq approach, when combined with mutant analysis and functional validation, can be a powerful method to identify genes involved in a specific developmental process, in this case Q descendant posterior migration. These genes could act either autonomously in the Q cells, or non-autonomously in other cells that express MAB-5. The identities of the genes regulated by MAB-5 indicate that MAB-5 acts by modifying interactions with the basement membrane, resulting in posterior versus anterior migration.
When the group practice breaks up: a qualitative study
Authors: Marechal François , Schmidt Dorothée , Lasserre Evelyne , Letrilliart Laurent
Published: May 2013

Background

Group practices are increasingly common for primary care physicians worldwide. Although breakups are likely to happen frequently within group practices, their process has not been studied to date. The aims of this study were therefore to explore the reasons for breakups of group practices of general practitioners and to describe the associated feelings.

Methods

We conducted a qualitative study consisting of in-depth interviews of 21 general practitioners and one secretary from past group practices in the Rhône-Alpes region, France, who experienced a breakup.

Results

When getting started in group practice for the first time, young doctors did not feel ready and supported, and did not necessarily share the same expectations as their partners. The reasons for the breakups involved imbalances within the groups, contrasting working and management styles, and breakdowns in communication. The breakup process often generated long-persistent feelings of suffering and failure for almost every partner who experienced a breakup, particularly for the partner who was leaving.

Conclusions

Weakening factors exist from the very beginning of a partnership, and problems are likely to increase at every change or event occurring in the group. We provide several recommendations, including fair management, a shared project based on a precise contract, the consultation of third parties as necessary and, in the worst case scenario, leaving the group practice in time.
Clinical and economic burden of invasive pneumococcal disease in adults: a multicenter hospital-based study
Authors: Song Joon Young , Choi Jun Yong , Lee Jin Soo , Bae In-Gyu , Kim Young Keun , Sohn Jang Wook , Jo Yu Mi , Choi Won Suk , Lee Jacob , Park Kyung Hwa , Kim Woo Joo , Cheong Hee Jin
Published: May 2013

Background

Streptococcus pneumoniae causes a broad spectrum of illnesses ranging from mild upper respiratory tract infections to invasive pneumococcal disease (IPD). Quantitative data on the burden of pneumococcal disease, important for the establishment of appropriate vaccination strategies, is currently lacking in adults.

Methods

This multicenter, retrospective cohort study was designed to estimate the clinical and economic burden of IPD in adults over the last decade. Data were collected from patients with IPD at 10 university hospitals in South Korea. We estimated the proportion of IPD among all hospitalized patients, the case fatality rate, and the direct medical costs of IPD. Data were further analyzed according to age and risk groups.

Results

During the study period, 970 patients with IPD were identified. The mean age for all patients was 60.9 years; patients aged 50–64 years (33.0%) were most numerous, followed by those aged 65–74 years (27.4%). Overall, the proportion of IPD was 0.36 cases/1000 hospitalized patients and the case fatality rate was 30.9%, which increased significantly with age (p < 0.01). The mean direct medical costs were estimated to be US $7,452 without a difference between age and risk groups. On multivariate analysis, old age, advanced ECOG performance status, bacteremic pneumonia, and nosocomial infection were independent risk factors of 30-day case fatality.

Conclusions

The clinical disease burden of IPD increased significantly with age and direct medical costs from IPD were substantial, regardless of age and co-morbid conditions. The current age-based vaccination strategy appears to be appropriate.
Factors associated with cervical cancer screening uptake among Inuit women in Nunavik, Quebec, Canada
Authors: Cerigo Helen , Coutlée Francois , Franco Eduardo L , Brassard Paul
Published: May 2013

Background

The Canadian circumpolar Inuit population has a higher incidence rate of cervical cancer than the general population and the majority of cases occur among underscreened women. The objectives of this study were to determine Pap smear utilization rates and to determine factors associated with time-inappropriate use of cervical cancer screening among a cohort of Inuit women from Nunavik, Quebec, Canada.

Methods

This study utilizes baseline information collected from a cohort formed between January 2002 and December 2007 to study the natural history of HPV among Inuit women aged 21–69 years in Nunavik, Quebec. Cervical cancer screening history and other variables were obtained from a baseline questionnaire and medical chart review. Unconditional logistic regression was used to estimate the odds ratios and 95% confidence intervals for potential predictors of not having a Pap smear within the previous 3 years prior to cohort entry.

Results

A total of 403 Inuit women who had a baseline questionnaire and chart review were included. The mean age of the study population was 34.2 years. In the three years prior to study entry, 25% of women did not have a Pap smear. Older age and never giving birth were significant predictors of time-inappropriate Pap smear use.

Conclusions

Our results suggest that older women and women who are not accessing reproductive care have a lower compliance with time-appropriate cervical cancer screening and future research should address potential strategies to increase screening coverage among this group.
Evaluation of the inhibition of carbohydrate hydrolysing enzymes, antioxidant activity and polyphenolic content of extracts of ten African Ficus species (Moraceae) used traditionally to treat diabetes
Authors: Olaokun Oyinlola O , McGaw Lyndy J , Eloff Jacobus N , Naidoo Vinny
Published: May 2013

Background

Some Ficus species have been used in traditional African medicine in the treatment of diabetes. The antidiabetic potential of certain species has been confirmed in vivo but the mechanism of activity remains uncertain. The aim of this study was to determine the activity and to investigate the mechanism of antidiabetic activity of ten selected Ficus species through inhibition of α-amylase and α-glucosidase activity, and the possible relationship between these activities, the total polyphenolic content and the antioxidant activity.

Methods

Dried acetone leaf extracts were reconstituted with appropriate solvents and used to determine total polyphenolic content antioxidant activity, α-amylase and α-glucosidase inhibitory activity.

Results

The crude acetone extract of F. lutea had the highest polyphenolic content (56.85 ± 1.82 mg GAE/g of dry material) and the strongest antioxidant activity with a TEAC value of 4.80 ± 0.90. The antioxidant activity of the acetone extracts of the Ficus species may not be ascribed to total polyphenolic content alone. The crude extract at a concentration of 0.5 mg/ml of F. lutea (64.3 ± 3.6%) had the best α-glucosidase (sucrase) inhibitory activity. The EC50 of F. lutea (290 ± 111 μg/ml) was not significantly different from that of F. sycomorus (217 ± 69 μg/ml). The α-amylase inhibitory activity of F. lutea (95.4 ± 1.2%) at a concentration of 1 mg/ml was the highest among the Ficus species screened. The EC50 for F. lutea (9.42 ± 2.01 μ g/ml), though the highest, was not significantly different (p < 0.05) from that of F. craterostoma and F. natalensis. It was apparent that the crude acetone extract of F. lutea is a partially non-competitive inhibitor of α-amylase and α-glucosidase. Based on correlation coefficients polyphenolics may be responsible for α-glucosidase activity but probably not for α-amylase activity.

Conclusion

Antidiabetic activity potential via inhibition of α-amylase and α-glucosidase was discovered in Ficus lutea which has not been previously reported. The acetone extract of the leaves was high in total polyphenolic content and antioxidant activity, and was a potent inhibitor of α-amylase activity. Research is underway to isolate the active compound(s) responsible for the antidiabetic activity and to confirm the in vitro antidiabetic activity and to investigate in vitro toxicity.
Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients
Authors: Cabré Anna , Valdovinos Pilar , Lázaro Iolanda , Bonet Gil , Bardají Alfredo , Masana Lluís
Published: May 2013

Background

Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF).

Methods

We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons.

Results

In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF.

Conclusions

FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients.
Effects of 24-week treatment with acarbose on glucagon-like peptide 1 in newly diagnosed type 2 diabetic patients: a preliminary report
Authors: Zheng Miao-yan , Yang Ju-hong , Shan Chun-yan , Zhou Hong-tao , Xu Yan-guang , Wang Ying , Ren Hui-zhu , Chang Bao-cheng , Chen Li-ming
Published: May 2013

Background

Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. However, the underlying mechanisms of this effect are unclear. AGIs were recently suggested to participate in stimulating glucagon-like peptide 1 (GLP-1) secretion. We therefore examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D).

Methods

Blood was drawn from 24 subjects (14 male, 10 female, age: 50.7 ± 7.36 years, BMI: 26.64 ± 3.38 kg/m2, GHbA1c: 7.00 ± 0.74%) with drug-naïve T2D at 0 and 120 min following a standard mixed meal for the measurements of active GLP-1, NO and NOS. The CIMT was measured prior to and following 24 weeks of acarbose monotherapy (mean dose: 268 mg daily).

Results

Following 24 weeks of acarbose treatment, both fasting and postprandial plasma GLP-1 levels were increased. In patients with increased postprandial GLP-1 levels, serum NO levels and NOS activities were also significantly increased and were positively related to GLP-1 levels. Although the CIMT was not significantly altered following treatment with acarbose, a decreased CIMT was negatively correlated with increased GLP-1 levels.

Conclusions

Twenty-four weeks of acarbose monotherapy in newly diagnosed patients with T2D is associated with significantly increased levels of both fasting and postprandial GLP-1 as well as significantly increased NO levels and NOS activity for those patients in whom postprandial GLP-1 levels were increased. Therefore, the benefits of acarbose on cardiovascular risk may be related to its stimulation of GLP-1 secretion.
Lactic acid fermentation as a tool to enhance the functional features of Echinacea spp
Authors: Rizzello Carlo Giuseppe , Coda Rossana , Macías Davinia Sánchez , Pinto Daniela , Marzani Barbara , Filannino Pasquale , Giuliani Giammaria , Paradiso Vito Michele , Di Cagno Raffaella , Gobbetti Marco
Published: May 2013

Background

Extracts and products (roots and/or aerial parts) fromEchinaceassp. represent a profitable market sector for herbal medicines thanks to different functional features. Alkamides and polyacetylenes, phenols like caffeic acid and its derivatives, polysaccharides and glycoproteins are the main bioactive compounds ofEchinaceaspp. This study aimed at investigating the capacity of selected lactic acid bacteria to enhance the antimicrobial, antioxidant and immune-modulatory features ofE. purpureawith the prospect of its application as functional food, dietary supplement or pharmaceutical preparation.

Results

Echinacea purpureasuspension (5%, wt/vol) in distilled water, containing 0.4% (wt/vol) yeast extract, was fermented withLactobacillus plantarumPOM1, 1MR20 or C2, previously selected from plant materials. Chemically acidified suspension, without bacterial inoculum, was used as the control to investigate functional features.Echinaceasuspension fermented withLb. plantarumC2 exhibited a marked antimicrobial activity towards Gram-positive and -negative bacteria. Compared to control, the water-soluble extract fromEchinaceasuspension fermented withLactobacillus plantarum1MR20 showed twice time higher radical scavenging activity on DPPH. Almost the same was found for the inhibition of oleic acid peroxidation. The methanol extract fromEchinaceasuspension had inherent antioxidant features but the activity of extract from the sample fermented with strain 1MR20 was the highest. The antioxidant activities were confirmed on Balb 3T3 mouse fibroblasts.Lactobacillus plantarumC2 and 1MR20 were used in association to fermentEchinaceasuspension, and the water-soluble extract was subjected to ultra-filtration and purification through RP-FPLC. The antioxidant activity was distributed in a large number of fractions and proportional to the peptide concentration. The antimicrobial activity was detected only in one fraction, further subjected to nano-LC-ESI-MS/MS. A mixture of eight peptides was identified, corresponding to fragments of plantaricins PlnH or PlnG. Treatments with fermentedEchinaceasuspension exerted immune-modulatory effects on Caco-2 cells. The fermentation withLb. plantarum1MR20 or with the association between strains C2 and 1MR20 had the highest effect on the expression ofTNF-α gene.

Conclusions

E. purpureasubjected to lactic acid fermentation could be suitable for novel applications as functional food dietary supplements or pharmaceutical preparations.