bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient safety: a core value of nursing - so why is achieving it so difficult?
Authors: Reid Jane , Catchpole Ken
Published: May 2011

Patient safety in the perioperative setting is determined by many interdependent factors including reliable systems, good teamwork, psychological safety, optimal communications and most crucially shared vision and goals. The necessary organizational, environmental and behavioural conditions for quality care are not new and were in fact known to Florence Nightingale as much as 150 years ago. As noted by Nightingale, and something that remains unchanged today, the greatest threat to patient safety are the frailties of the human condition, complacent attitudes and unconscious behaviours. Recognizing that error is normal and somewhat inevitable, given the complexity of modern surgery, is undoubtedly the first step to mitigating error and harm, and the basis from which to tackle variability and sub-optimal conditions to deliver quality improvement.
Integrating quality and safety science in nursing education and practice
Authors: Sherwood Gwen
Published: May 2011

Worldwide, health care delivery systems are applying new quality and safety science in response to startling reports of negative patient outcomes. Many health care professionals lack the knowledge, skills and attitudes to change the systems in which they work, calling for radical redesign of nursing education to integrate new safety and quality science. This paper describes the transformation underway in nursing education in the United States to integrate quality and safety competencies through the Quality and Safety Education for Nurses (QSEN) project. A national expert panel defined the competencies and surveyed US schools of nursing to assess current implementation. To model the changes needed, a 15-school Pilot Learning Collaborative completed demonstration projects and surveyed graduating students to self-assess their achievement of the competencies. A Delphi process assessed level and placement of the competencies in the curriculum to offer educators a blueprint for spreading across curricula. Specialty organisations are cross-mapping the competencies for graduate education, educational standards have incorporated the competencies into their essentials documents, and a train the trainer faculty development model is now helping educators transform curriculum. Two key questions emerge from these findings: Are any of these projects replicable in other settings? Will these competencies translate across borders?
Biological outcome measurements for behavioral interventions in multiple sclerosis
Authors: Fischer Anja , Heesen Christoph , Gold Stefan M.
Published: May 2011

Behavioral interventions including exercise, stress management, patient education, psychotherapy and multidisciplinary neurorehabilitation in general are receiving increasing recognition in multiple sclerosis (MS) clinical practice and research. Most scientific evaluations of these approaches have focused on psychosocial outcome measures such as quality of life, fatigue or depression. However, it is becoming increasingly clear that neuropsychiatric symptoms of MS are at least partially mediated by biological processes such as inflammation, neuroendocrine dysfunction or regional brain damage. Thus, successful treatment of these symptoms with behavioral approaches could potentially also affect the underlying biology. Rigidly designed scientific studies are needed to explore the potential of such interventions to affect MS pathology and biological pathways linked to psychological and neuropsychiatric symptoms of MS. Such studies need to carefully select outcome measures on the behavioral level that are likely to be influenced by the specific intervention strategy and should include biomarkers with evidence for an association with the outcome parameter in question. In this overview, we illustrate how biological and psychological outcome parameters can be combined to evaluate behavioral interventions. We focus on two areas of interest as potential targets for behavioral interventions: depression and fatigue.
The Fate of Oral Glucosamine Traced by 13C Labeling in the Dog
Authors: Dodge George R. , Regatte Ravinder R. , Noyszewski Elizabeth A. , Hall Jeffery O. , Sharma Akella V. , Callaway D. Allen , Reddy Ravinder
Published: May 2011

Objective:

It has remained ambiguous as to whether oral dosing of glucosamine (GlcN) would make its way to the joint and affect changes in the cartilage, particularly the integrity of cartilage and chondrocyte function. The objective of this study was to trace the fate of orally dosed GlcN and determine definitively if GlcN was incorporated into cartilage proteoglycans.

Design:

Two dogs were treated with 13C-GlcN-HCl by oral dosing (500 mg/dog/d for 2 weeks and 250 mg/dog/d for 3 weeks). Cartilage was harvested from the tibial plateau and femoral condyles along with tissue specimens from the liver, spleen, heart, kidney, skin, skeletal muscle, lung, and costal cartilage. Percentages of 13C and 13C-GlcN present in each tissue sample were determined by inductively coupled plasma mass spectroscopy (ICP-MS) and nuclear magnetic resonance spectroscopy, respectively.

Results:

In the case of dog 1 (2-week treatment), there was an increase of 2.3% of 13C present in the articular cartilage compared to the control and an increase of 1.6% of 13C in dog 2 compared to control. As to be expected, the highest percentage of 13C in the other tissues tested was found in the liver, and the remaining tissues had percentages of 13C less than that of articular cartilage.

Conclusion:

The results are definitive and for the first time provide conclusive evidence that orally given GlcN can make its way through the digestive tract and be used by chondrocytes in joint cartilage, thereby potentially having an effect on the available GlcN for proteoglycan biosynthesis.
Cytokine release from innate immune cells: association with diverse membrane trafficking pathways
Authors: Lacy Paige , Stow Jennifer L.
Published: May 2011

Cytokines released from innate immune cells play key roles in the regulation of the immune response. These intercellular messengers are the source of soluble regulatory signals that initiate and constrain inflammatory responses to pathogens and injury. Although numerous studies describe detailed signaling pathways induced by cytokines and their specific receptors, there is little information on the mechanisms that control the release of cytokines from different cell types. Indeed, the pathways, molecules, and mechanisms of cytokine release remain a “black box” in immunology. Here, we review research findings and new approaches that have begun to generate information on cytokine trafficking and release by innate immune cells in response to inflammatory or infectious stimuli. Surprisingly complex machinery, multiple organelles, and specialized membrane domains exist in these cells to ensure the selective, temporal, and often polarized release of cytokines in innate immunity.
Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group
Authors: Matloub Yousif , Bostrom Bruce C. , Hunger Stephen P. , Stork Linda C. , Angiolillo Anne , Sather Harland , La Mei , Gastier-Foster Julie M. , Heerema Nyla A. , Sailer Scott , Buckley Patrick J. , Thomson Blythe , Cole Catherine , Nachman James B. , Reaman Gregory , Winick Naomi , Carroll William L. , Devidas Meenakshi , Gaynon Paul S.
Published: May 2011

Children's Cancer Group-1991 selected 2 components from the Children's Cancer Group studies shown to be effective in high-risk acute lymphoblastic leukemia and examined them in children with National Cancer Institute standard-risk acute B-precursor lymphoblastic leukemia. These were (1) vincristine and escalating IV methotrexate (MTX) without leucovorin rescue during the interim maintenance (IM) phases and (2) addition of a second delayed intensification (DI) phase. Eligible patients (n = 2078) were randomly assigned to regimens containing either oral (PO) MTX, PO mercaptopurine, dexamethasone, and vincristine or IV MTX during IM phases, and regimens with either single DI or double DI. Five-year event-free survival (EFS) and overall survival for patients on the PO MTX arms were 88.7% ± 1.4% and 96% ± 0.9% versus 92.6% ± 1.2% and 96.5% ± 0.8% for those on the IV MTX arms (P = .009, P = .66). Five-year EFS and overall survival for patients who received single DI were 90.9% ± 1.3% and 97.1% ± 0.8% versus 90.5% ± 1.3% and 95.4% ± 3.8% for those who received double DI (P = .71, P = .12). No advantage was found for a second DI; however, replacement of PO MTX, PO mercaptopurine, vincristine, and dexamethasone during IM with vincristine and escalating IV MTX improved EFS.
BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet
Authors: Soverini Simona , Hochhaus Andreas , Nicolini Franck E. , Gruber Franz , Lange Thoralf , Saglio Giuseppe , Pane Fabrizio , Müller Martin C. , Ernst Thomas , Rosti Gianantonio , Porkka Kimmo , Baccarani Michele , Cross Nicholas C. P. , Martinelli Giovanni
Published: May 2011

Mutations in the Bcr-Abl kinase domain may cause, or contribute to, resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients. Recommendations aimed to rationalize the use of BCR-ABL mutation testing in chronic myeloid leukemia have been compiled by a panel of experts appointed by the European LeukemiaNet (ELN) and European Treatment and Outcome Study and are here reported. Based on a critical review of the literature and, whenever necessary, on panelists' experience, key issues were identified and discussed concerning: (1) when to perform mutation analysis, (2) how to perform it, and (3) how to translate results into clinical practice. In chronic phase patients receiving imatinib first-line, mutation analysis is recommended only in case of failure or suboptimal response according to the ELN criteria. In imatinib-resistant patients receiving an alternative TKI, mutation analysis is recommended in case of hematologic or cytogenetic failure as provisionally defined by the ELN. The recommended methodology is direct sequencing, although it may be preceded by screening with other techniques, such as denaturing-high performance liquid chromatography. In all the cases outlined within this abstract, a positive result is an indication for therapeutic change. Some specific mutations weigh on TKI selection.
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Authors: Hao Yi , O'Neill Patrick , Naradikian Martin S. , Scholz Jean L. , Cancro Michael P.
Published: May 2011

We have discovered a distinct mature B-cell subset that accumulates with age, which we have termed age-associated B cells. These cells comprise up to 30% of mature B cells by 22 months. Despite sharing some features with other mature B-cell subsets, they are refractory to BCR and CD40 stimulation. Instead, they respond to TLR9 or TLR7 stimulation and divide maximally on combined BCR and TLR ligation, leading to Ig production and preferential secretion of IL-10 and IL-4. Although similar to follicular B cells in both B-lymphocyte stimulator (BLyS) receptor expression and BLyS binding capacity, these cells do not rely on BLyS for survival. They are neither cycling nor the result of intrinsically altered B lymphopoiesis in aged BM, but instead appear to be generated from mature B cells that exhaustively expand during the individual's lifetime. Finally, they present Ag effectively and favor polarization to a TH17 profile. Together, these findings reveal that while the magnitude of the mature primary B-cell niche is maintained with age, it is increasingly occupied by cells refractory to BCR-driven activation yet responsive to innate receptor stimulation.
Differential effects of HIV viral load and CD4 count on proliferation of naive and memory CD4 and CD8 T lymphocytes
Authors: Srinivasula Sharat , Lempicki Richard A. , Adelsberger Joseph W. , Huang Chiung-Yu , Roark Joshua , Lee Philip I. , Rupert Adam , Stevens Randy , Sereti Irini , Lane H. Clifford , Di Mascio Michele , Kovacs Joseph A.
Published: May 2011

We previously showed that HIV infection leads to expansion of a rapidly proliferating pool (s1) of CD4 and CD8 T lymphocytes. In the current study, we used in vivo labeling with bromodeoxyuridine to characterize the kinetics of naive, memory, and activated (HLA-DR+/CD38+) subpopulations of CD4 and CD8 T lymphocytes, and to examine the relationship between kinetic parameters and baseline CD4 counts, HIV viral load, potential markers of microbial translocation, and cytokine levels. Activated cells showed the highest proliferation rates, followed by effector and central memory cells, with naive cells showing the lowest rates, for both CD4 and CD8 T cells. HIV viral load correlated with s1 of CD4 and CD8 effector memory cells, as well as CD8 naive cells, whereas CD4 cell counts correlated inversely with naive CD4 s1. Endotoxin levels showed a weak negative association with CD4 but not CD8 s1. INF-γ and TNF-α were associated with s1 for CD4 and CD8 cells, respectively. Thus, HIV is the primary driving force behind the activation and proliferation of most subsets of both CD4 and CD8 T lymphocytes, whereas naive CD4 cell proliferation likely represents a homeostatic response. Microbial translocation does not appear to play an important role in this proliferation.
Infection with the gastrointestinal nematode Ostertagia ostertagi in cattle affects mucus biosynthesis in the abomasum
Authors: Rinaldi Manuela , Dreesen Leentje , Hoorens Prisca R , Li Robert W , Claerebout Edwin , Goddeeris Bruno , Vercruysse Jozef , Van Den Broek Wim , Geldhof Peter
Published: May 2011

The mucus layer in the gastrointestinal (GI) tract is considered to be the first line of defense to the external environment. Alteration in mucus components has been reported to occur during intestinal nematode infection in ruminants, but the role of mucus in response to abomasal parasites remains largely unclear. The aim of the current study was to analyze the effects of anOstertagia ostertagiinfection on the abomasal mucus biosynthesis in cattle. Increased gene expression ofMUC1,MUC6andMUC20was observed, whileMUC5ACdid not change during infection. Qualitative changes of mucins, related to sugar composition, were also observed. AB-PAS and HID-AB stainings highlighted a decrease in neutral and an increase in acidic mucins, throughout the infection. Several genes involved in mucin core structure synthesis, branching and oligomerization, such asGCNT3,GCNT4,A4GNTand protein disulphide isomerases were found to be upregulated. Increase in mucin fucosylation was observed using the lectin UEA-I and through the evaluation of fucosyltransferases gene expression levels. Finally, transcription levels of 2 trefoil factors,TFF1andTFF3, which are co-expressed with mucins in the GI tract, were also found to be significantly upregulated in infected animals. Although the alterations in mucus biosynthesis started early during infection, the biggest effects were found when adult worms were present on the surface of the abomasal mucosa and are likely caused by the alterations in mucosal cell populations, characterized by hyperplasia of mucus secreting cells.
Transcriptional landscape of bone marrow-derived very small embryonic-like stem cells during hypoxia
Authors: Gharib Sina A , Khalyfa Abdelnaby , Kucia Magdalena J , Dayyat Ehab A , Kim Jinkwan , Clair Heather B , Gozal David
Published: May 2011

Background

Hypoxia is a ubiquitous feature of many lung diseases and elicits cell-specific responses. While the effects of hypoxia on stem cells have been examined under in vitro conditions, the consequences of in vivo oxygen deprivation have not been studied.

Methods

We investigated the effects of in vivo hypoxia on a recently characterized population of pluripotent stem cells known as very small embryonic-like stem cells (VSELs) by whole-genome expression profiling and measuring peripheral blood stem cell chemokine levels.

Results

We found that exposure to hypoxia in mice mobilized VSELs from the bone marrow to peripheral blood, and induced a distinct genome-wide transcriptional signature. Applying a computationally-intensive methodology, we identified a hypoxia-induced gene interaction network that was functionally enriched in a diverse array of programs including organ-specific development, stress response, and wound repair. Topographic analysis of the network highlighted a number of densely connected hubs that may represent key controllers of stem cell response during hypoxia and, therefore, serve as putative targets for altering the pathophysiologic consequences of hypoxic burden.

Conclusions

A brief exposure to hypoxia recruits pluripotent stem cells to the peripheral circulation and actives diverse transcriptional programs that are orchestrated by a selective number of key genes.
The midgut transcriptome of Phlebotomus (Larroussius) perniciosus, a vector of Leishmania infantum: comparison of sugar fed and blood fed sand flies
Authors: Dostálová Anna , Votýpka Jan , Favreau Amanda J , Barbian Kent D , Volf Petr , Valenzuela Jesus G , Jochim Ryan C
Published: May 2011

Background

Parasite-vector interactions are fundamental in the transmission of vector-borne diseases such as leishmaniasis. Leishmania development in the vector sand fly is confined to the digestive tract, where sand fly midgut molecules interact with the parasites. In this work we sequenced and analyzed two midgut-specific cDNA libraries from sugar fed and blood fed female Phlebotomus perniciosus and compared the transcript expression profiles.

Results

A total of 4111 high quality sequences were obtained from the two libraries and assembled into 370 contigs and 1085 singletons. Molecules with putative roles in blood meal digestion, peritrophic matrix formation, immunity and response to oxidative stress were identified, including proteins that were not previously reported in sand flies. These molecules were evaluated relative to other published sand fly transcripts. Comparative analysis of the two libraries revealed transcripts differentially expressed in response to blood feeding. Molecules up regulated by blood feeding include a putative peritrophin (PperPer1), two chymotrypsin-like proteins (PperChym1 and PperChym2), a putative trypsin (PperTryp3) and four putative microvillar proteins (PperMVP1, 2, 4 and 5). Additionally, several transcripts were more abundant in the sugar fed midgut, such as two putative trypsins (PperTryp1 and PperTryp2), a chymotrypsin (PperChym3) and a microvillar protein (PperMVP3). We performed a detailed temporal expression profile analysis of the putative trypsin transcripts using qPCR and confirmed the expression of blood-induced and blood-repressed trypsins. Trypsin expression was measured in Leishmania infantum-infected and uninfected sand flies, which identified the L. infantum-induced down regulation of PperTryp3 at 24 hours post-blood meal.

Conclusion

This midgut tissue-specific transcriptome provides insight into the molecules expressed in the midgut of P. perniciosus, an important vector of visceral leishmaniasis in the Old World. Through the comparative analysis of the libraries we identified molecules differentially expressed during blood meal digestion. Additionally, this study provides a detailed comparison to transcripts of other sand flies. Moreover, our analysis of putative trypsins demonstrated that L. infantum infection can reduce the transcript abundance of trypsin PperTryp3 in the midgut of P. perniciosus.
Identification of gene expression changes associated with the initiation of diapause in the brain of the cotton bollworm, Helicoverpa armigera
Authors: Bao Bin , Xu Wei-Hua
Published: May 2011

Background

Diapause, a state of arrested development accompanied by a marked decrease of metabolic rate, helps insects to overcome unfavorable seasons. Helicoverpa armigera (Har) undergoes pupal diapause, but the molecular mechanism of diapause initiation is unclear. Using suppression subtractive hybridization (SSH), we investigated differentially expressed genes in diapause- and nondiapause-destined pupal brains at diapause initiation.

Results

We constructed two SSH libraries (forward, F and reverse, R) to isolate genes that are up-regulated or down-regulated at diapause initiation. We obtained 194 unique sequences in the F library and 115 unique sequences in the R library. Further, genes expression at the mRNA and protein level in diapause- and nondiapause-destined pupal brains were confirmed by RT-PCR, Northern blot or Western blot analysis. Finally, we classified the genes and predicted their possible roles at diapause initiation.

Conclusion

Differentially expressed genes at pupal diapause initiation are possibly involved in the regulation of metabolism, energy, stress resistance, signaling pathways, cell cycle, transcription and translation.
Genome-wide dynamics of a bacterial response to antibiotics that target the cell envelope
Authors: Hesketh Andy , Hill Chris , Mokhtar Jehan , Novotna Gabriela , Tran Ngat , Bibb Mervyn , Hong Hee-Jeon
Published: May 2011

Background

A decline in the discovery of new antibacterial drugs, coupled with a persistent rise in the occurrence of drug-resistant bacteria, has highlighted antibiotics as a diminishing resource. The future development of new drugs with novel antibacterial activities requires a detailed understanding of adaptive responses to existing compounds. This study uses Streptomyces coelicolor A3(2) as a model system to determine the genome-wide transcriptional response following exposure to three antibiotics (vancomycin, moenomycin A and bacitracin) that target distinct stages of cell wall biosynthesis.

Results

A generalised response to all three antibiotics was identified which involves activation of transcription of the cell envelope stress sigma factor σE, together with elements of the stringent response, and of the heat, osmotic and oxidative stress regulons. Attenuation of this system by deletion of genes encoding the osmotic stress sigma factor σB or the ppGpp synthetase RelA reduced resistance to both vancomycin and bacitracin. Many antibiotic-specific transcriptional changes were identified, representing cellular processes potentially important for tolerance to each antibiotic. Sensitivity studies using mutants constructed on the basis of the transcriptome profiling confirmed a role for several such genes in antibiotic resistance, validating the usefulness of the approach.

Conclusions

Antibiotic inhibition of bacterial cell wall biosynthesis induces both common and compound-specific transcriptional responses. Both can be exploited to increase antibiotic susceptibility. Regulatory networks known to govern responses to environmental and nutritional stresses are also at the core of the common antibiotic response, and likely help cells survive until any specific resistance mechanisms are fully functional.
Comprehensive transcriptome analysis of the highly complex Pisum sativum genome using next generation sequencing
Authors: Franssen Susanne U , Shrestha Roshan P , Bräutigam Andrea , Bornberg-Bauer Erich , Weber Andreas PM
Published: May 2011

Background

The garden pea, Pisum sativum, is among the best-investigated legume plants and of significant agro-commercial relevance. Pisum sativum has a large and complex genome and accordingly few comprehensive genomic resources exist.

Results

We analyzed the pea transcriptome at the highest possible amount of accuracy by current technology. We used next generation sequencing with the Roche/454 platform and evaluated and compared a variety of approaches, including diverse tissue libraries, normalization, alternative sequencing technologies, saturation estimation and diverse assembly strategies. We generated libraries from flowers, leaves, cotyledons, epi- and hypocotyl, and etiolated and light treated etiolated seedlings, comprising a total of 450 megabases. Libraries were assembled into 324,428 unigenes in a first pass assembly.

A second pass assembly reduced the amount to 81,449 unigenes but caused a significant number of chimeras. Analyses of the assemblies identified the assembly step as a major possibility for improvement. By recording frequencies of Arabidopsis orthologs hit by randomly drawn reads and fitting parameters of the saturation curve we concluded that sequencing was exhaustive. For leaf libraries we found normalization allows partial recovery of expression strength aside the desired effect of increased coverage. Based on theoretical and biological considerations we concluded that the sequence reads in the database tagged the vast majority of transcripts in the aerial tissues. A pathway representation analysis showed the merits of sampling multiple aerial tissues to increase the number of tagged genes. All results have been made available as a fully annotated database in fasta format.

Conclusions

We conclude that the approach taken resulted in a high quality - dataset which serves well as a first comprehensive reference set for the model legume pea. We suggest future deep sequencing transcriptome projects of species lacking a genomics backbone will need to concentrate mainly on resolving the issues of redundancy and paralogy during transcriptome assembly.
Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
Authors: Parisi Fabio , Ariyan Stephan , Narayan Deepak , Bacchiocchi Antonella , Hoyt Kathleen , Cheng Elaine , Xu Fang , Li Peining , Halaban Ruth , Kluger Yuval
Published: May 2011

Background

Genomic aberrations can be used to determine cancer diagnosis and prognosis. Clinically relevant novel aberrations can be discovered using high-throughput assays such as Single Nucleotide Polymorphism (SNP) arrays and next-generation sequencing, which typically provide aggregate signals of many cells at once. However, heterogeneity of tumor subclones dramatically complicates the task of detecting aberrations.

Results

The aggregate signal of a population of subclones can be described as a linear system of equations. We employed a measure of allelic imbalance and total amount of DNA to characterize each locus by the copy number status (gain, loss or neither) of the strongest subclonal component. We designed simulated data to compare our measure to existing approaches and we analyzed SNP-arrays from 30 melanoma samples and transcriptome sequencing (RNA-Seq) from one melanoma sample.

We showed that any system describing aggregate subclonal signals is underdetermined, leading to non-unique solutions for the exact copy number profile of subclones. For this reason, our illustrative measure was more robust than existing Hidden Markov Model (HMM) based tools in inferring the aberration status, as indicated by tests on simulated data. This higher robustness contributed in identifying numerous aberrations in several loci of melanoma samples. We validated the heterogeneity and aberration status within single biopsies by fluorescent in situ hybridization of four affected and transcriptionally up-regulated genes E2F8, ETV4, EZH2 and FAM84B in 11 melanoma cell lines. Heterogeneity was further demonstrated in the analysis of allelic imbalance changes along single exons from melanoma RNA-Seq.

Conclusions

These studies demonstrate how subclonal heterogeneity, prevalent in tumor samples, is reflected in aggregate signals measured by high-throughput techniques. Our proposed approach yields high robustness in detecting copy number alterations using high-throughput technologies and has the potential to identify specific subclonal markers from next-generation sequencing data.
Differential phylogenetic expansions in BAHD acyltransferases across five angiosperm taxa and evidence of divergent expression among Populus paralogues
Authors: Tuominen Lindsey K , Johnson Virgil E , Tsai Chung-Jui
Published: May 2011

Background

BAHD acyltransferases are involved in the synthesis and elaboration of a wide variety of secondary metabolites. Previous research has shown that characterized proteins from this family fall broadly into five major clades and contain two conserved protein motifs. Here, we aimed to expand the understanding of BAHD acyltransferase diversity in plants through genome-wide analysis across five angiosperm taxa. We focus particularly on Populus, a woody perennial known to produce an abundance of secondary metabolites.

Results

Phylogenetic analysis of putative BAHD acyltransferase sequences from Arabidopsis, Medicago, Oryza, Populus, and Vitis, along with previously characterized proteins, supported a refined grouping of eight major clades for this family. Taxon-specific clustering of many BAHD family members appears pervasive in angiosperms. We identified two new multi-clade motifs and numerous clade-specific motifs, several of which have been implicated in BAHD function by previous structural and mutagenesis research. Gene duplication and expression data for Populus-dominated subclades revealed that several paralogous BAHD members in this genus might have already undergone functional divergence.

Conclusions

Differential, taxon-specific BAHD family expansion via gene duplication could be an evolutionary process contributing to metabolic diversity across plant taxa. Gene expression divergence among some Populus paralogues highlights possible distinctions between their biochemical and physiological functions. The newly discovered motifs, especially the clade-specific motifs, should facilitate future functional study of substrate and donor specificity among BAHD enzymes.
Cloning, purification, and functional characterization of Carocin S2, a ribonuclease bacteriocin produced by Pectobacterium carotovorum
Authors: Chan Yung-Chieh , Wu Jian-Li , Wu Huang-Pin , Tzeng Kuo-Ching , Chuang Duen-Yau
Published: May 2011

Background

Most isolates of Pectobacterium carotovorum subsp. carotovorum (Pcc) produce bacteriocins. In this study, we have determined that Pcc strain F-rif-18 has a chromosomal gene encoding the low-molecular-weight bacteriocin, Carocin S2, and that this bacteriocin inhibits the growth of a closely related strain. Carocin S2 is inducible by ultraviolet radiation but not by mutagenic agents such as mitomycin C.

Results

A carocin S2-defective mutant, TF1-2, was obtained by Tn5 insertional mutagenesis using F-rif-18. A 5706-bp DNA fragment was detected by Southern blotting, selected from a genomic DNA library, and cloned to the vector, pMS2KI. Two adjacent complete open reading frames within pMS2KI were sequenced, characterized, and identified as caroS2K and caroS2I, which respectively encode the killing protein and immunity protein. Notably, carocin S2 could be expressed not only in the mutant TF1-2 but also in Escherichia coli DH5α after entry of the plasmid pMS2KI. Furthermore, the C-terminal domain of CaroS2K was homologous to the nuclease domains of colicin D and klebicin D. Moreover, SDS-PAGE analysis showed that the relative mass of CaroS2K was 85 kDa and that of CaroS2I was 10 kDa.

Conclusion

This study shown that another nuclease type of bacteriocin was found in Pectobacterium carotovorum. This new type of bacteriocin, Carocin S2, has the ribonuclease activity of CaroS2K and the immunity protein activity of CaroS2I.
Gaining insight into benzodiazepine prescribing in General Practice in France: a data-based study
Authors: Rosman Sophia , Le Vaillant Marc , Pelletier-Fleury Nathalie
Published: May 2011

Background

In recent decades, benzodiazepine (BZD) prescriptions have been called into question in most European countries by physicians and health authorities alike, and guidelines on medical indications and treatment duration have been established to avoid long-term use and dependency. In France, many public policy measures have been implemented as BZDs are among the most prescribed medications. General practitioners (GPs) were identified by the Caisse d'Assurance Maladie (the French public health insurance fund) as high prescribers for these drugs. In this context, the aim of the study was to determine GPs' rates and to identify correlates of BZD and Z-drugs prescribing.

Methods

Data on patient characteristics, diagnoses and BZD prescriptions were drawn from French GPs' electronic medical records. These were accessed via the database which the Société Française de Médecine Générale, the French Society of General Practice, has been compiling since 1993 in a network of 90 GPs working mainly in solo practices. The participants in this network routinely register data in their daily practice. The present study examined 51,216 patients from 52 GP practices and we performed a multivariate logistic regression. The dependent variable was whether a patient was prescribed BZD at least once during 2006.

Results

In the present study, 12.5% of patients older than 18 were prescribed BZDs at least once during 2006 and the average (SD) was 2.6 (2.4) BZD prescriptions/patient/year. The adjusted odds (confidence interval) of having at least one BZD prescription were 1.20 (1.10 - 1.30) in patients older than 65; 1.05 (1.01 - 1.10) in women; 1.25 (1.17 - 1.33) in patients with associated comorbidities (cardiovascular diseases) and 1.76 (1.62 - 1.92) in heavy consumers of health care (more than 4 consultations with a GP per year).

Conclusions

The present study showed the persistence of high rates of BZD prescription by GPs, particularly in women and older patients, which highlights the difficulties of implementing effective public policies and the necessity of using new approaches enabling doctors and patients to understand the true relative advantages, disadvantages, and consequences of using these drugs and of non-pharmaceutical treatments.
What zinc supplementation does and does not achieve in diarrhea prevention: a systematic review and meta-analysis
Authors: Patel Archana B , Mamtani Manju , Badhoniya Neetu , Kulkarni Hemant
Published: May 2011

Background

Prevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea.

Methods

EMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality. The published RCTs were combined using random-effects meta-analyses, subgroup meta-analyses, meta-regression, cumulative meta-analyses and restricted meta-analyses to quantify and characterize the role of zinc supplementation with the afore stated outcomes.

Results

We found that zinc supplementation has a modest beneficial association (9% reduction) with incidence of diarrhea, a stronger beneficial association (19% reduction) with prevalence of diarrhea and occurrence of multiple diarrheal episodes (28% reduction) but there was significant unexplained heterogeneity across the studies for these associations. Age, continent of study origin, zinc salt and risk of bias contributed significantly to between studies heterogeneity. Zinc supplementation did not show statistically significant benefit in reducing the incidence of persistent diarrhea, dysentery or mortality. In most instances, the 95% prediction intervals for summary relative risk estimates straddled unity.

Conclusions

Demonstrable benefit of preventive zinc supplementation was observed against two of the five diarrhea-related outcomes but the prediction intervals straddled unity. Thus the evidence for a preventive benefit of zinc against diarrhea is inconclusive. Continued efforts are needed to better understand the sources of heterogeneity. The outcomes of zinc supplementation may be improved by identifying subgroups that need zinc supplementation.
Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study
Authors: Hill Lori D , Hilliard DaShaunda D , York Timothy P , Srinivas Sindhu , Kusanovic Juan P , Gomez Ricardo , Elovitz Michal A , Romero Roberto , Strauss Jerome F
Published: May 2011

Background

Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, ERAP2 expression is altered in first trimester placentas of women destined to develop preeclampsia.

Methods

A case-control design was used to test for associations between two SNPs in ERAP2, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal).

Results

We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (P = 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population.

Conclusions

We report an association between fetal ERAP2 and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, ERAP2 has now been associated with preeclampsia in three populations. This provides strong evidence that ERAP2 plays a role in the development of preeclampsia.
Using internet enabled mobile devices and social networking technologies to promote exercise as an intervention for young first episode psychosis patients
Authors: Killackey Eoin , Anda Anna Lee , Gibbs Martin , Alvarez-Jimenez Mario , Thompson Andrew , Sun Pamela , Baksheev Gennady N
Published: May 2011

Background

Young people with first episode psychosis are at an increased risk for a range of poor health outcomes. In contrast to the growing body of evidence that suggests that exercise therapy may benefit the physical and mental health of people diagnosed with schizophrenia, there are no studies to date that have sought to extend the use of exercise therapy among patients with first episode psychosis. The aim of the study is to test the feasibility and acceptability of an exercise program that will be delivered via internet enabled mobile devices and social networking technologies among young people with first episode psychosis.

Methods/Design

This study is a qualitative pilot study being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. Participants are young people aged 15-24 who are receiving clinical care at a specialist first episode psychosis treatment centre. Participants will also comprise young people from the general population. The exercise intervention is a 9-week running program, designed to gradually build a person's level of fitness to be able to run 5 kilometres (3 miles) towards the end of the program. The program will be delivered via an internet enabled mobile device. Participants will be asked to post messages about their running experiences on the social networking website, and will also be asked to attend three face-to-face interviews.

Discussion

This paper describes the development of a qualitative study to pilot a running program coupled with the use of internet enabled mobile devices among young people with first episode psychosis. If the program is found to be feasible and acceptable to patients, it is hoped that further rigorous evaluations will ultimately lead to the introduction of exercise therapy as part of an evidence-based, multidisciplinary approach in routine clinical care.
Institutional risk factors for norovirus outbreaks in Hong Kong elderly homes: a retrospective cohort study
Authors: Lin Hualiang , Ng Sammy , Chan Shelley , Chan Wai Man , Lee Krystal CK , Ho Suzanne C , Tian Linwei
Published: May 2011

Background

Most of the institutional outbreaks of norovirus in Hong Kong occur in elderly homes, the proportion being 69% in 2006. Residents in elderly homes are a special population seriously affected by norovirus infections, it is necessary to investigate the risk factors of the norovirus outbreaks in Hong Kong elderly homes at the facility level.

Methods

A cohort of 748 elderly homes was followed up from January 2005 to December 2007; each elderly home was treated as one observation unit and the outcome event was the norovirus outbreak. Cox regression models were fitted to estimate the rate ratio (RR) and 95% confidence interval (CI) for the potential risk factors.

Results

A total of 276 norovirus outbreaks were confirmed during the study period; the outbreak rate was 12.2 (95% CI: 9.9-14.6) per 100 home-years; elderly homes with a larger capacity (RR = 1.4, 95% CI: 1.3-1.5 (per 30-resident increment)), a higher staff-to-resident ratio (RR = 1.2, 95% CI: 1.1-1.3 (per 1/30 increment) and better wheelchair accessibility (RR = 2.0, 95% CI: 1.3-3.2) were found to have an elevated norovirus outbreak rate in Hong Kong elderly homes; Elderly homes with partitions between beds had a lower rate of norovirus outbreaks (RR = 0.6, 95% CI: 0.4-0.8).

Conclusions

Elderly home capacity, staff-to-resident ratio and wheelchair accessibility were risk factors for norovirus outbreaks in Hong Kong elderly homes. Partitions between beds were a protective factor of norovirus outbreaks. These results should be considered in the infection control in Hong Kong elderly homes.
Mortality by causes in HIV-infected adults: comparison with the general population
Authors: Aldaz Pablo , Moreno-Iribas Conchi , Egüés Nerea , Irisarri Fátima , Floristan Yugo , Sola-Boneta Julio , Martínez-Artola Víctor , Sagredo Mirian , Castilla Jesús
Published: May 2011

Background

We compared mortality by cause of death in HIV-infected adults in the era of combined antiretroviral therapy with mortality in the general population in the same age and sex groups.

Methods

Mortality by cause of death was analyzed for the period 1999-2006 in the cohort of persons aged 20-59 years diagnosed with HIV infection and residing in Navarre (Spain). This was compared with mortality from the same causes in the general population of the same age and sex using standardized mortality ratios (SMR).

Results

There were 210 deaths among 1145 persons diagnosed with HIV (29.5 per 1000 person-years). About 50% of these deaths were from AIDS. Persons diagnosed with HIV infection had exceeded all-cause mortality (SMR 14.0, 95% CI 12.2 to 16.1) and non-AIDS mortality (SMR 6.9, 5.7 to 8.5). The analysis showed excess mortality from hepatic disease (SMR 69.0, 48.1 to 78.6), drug overdose or addiction (SMR 46.0, 29.2 to 69.0), suicide (SMR 9.6, 3.8 to 19.7), cancer (SMR 3.2, 1.8 to 5.1) and cardiovascular disease (SMR 3.1, 1.3 to 6.1). Mortality in HIV-infected intravenous drug users did not change significantly between the periods 1999-2002 and 2003-2006, but it declined by 56% in non-injecting drug users (P = 0.007).

Conclusions

Persons with HIV infection continue to have considerable excess mortality despite the availability of effective antiretroviral treatments. However, excess mortality in the HIV patients has declined since these treatments were introduced, especially in persons without a history of intravenous drug use.
Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma
Authors: Ishikawa Nobuhisa , Mazur Witold , Toljamo Tuula , Vuopala Katri , Rönty Mikko , Horimasu Yasushi , Kohno Nobuoki , Kinnula Vuokko L
Published: May 2011

Background

KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD). Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history.

Methods

The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201). The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28), were analyzed by immunohistochemistry and digital image analysis.

Results

The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6.

Conclusions

KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.