bluuebunny/crossref_metadata_2025 huggingface dataset:
A genomic perspective on the potential of Actinobacillus succinogenes for industrial succinate production
Authors: McKinlay James B , Laivenieks Maris , Schindler Bryan D , McKinlay Anastasia A , Siddaramappa Shivakumara , Challacombe Jean F , Lowry Stephen R , Clum Alicia , Lapidus Alla L , Burkhart Kirk B , Harkins Victoria , Vieille Claire
Published: December 2010

Background

Succinate is produced petrochemically from maleic anhydride to satisfy a small specialty chemical market. If succinate could be produced fermentatively at a price competitive with that of maleic anhydride, though, it could replace maleic anhydride as the precursor of many bulk chemicals, transforming a multi-billion dollar petrochemical market into one based on renewable resources.Actinobacillus succinogenesnaturally converts sugars and CO2into high concentrations of succinic acid as part of a mixed-acid fermentation. Efforts are ongoing to maximize carbon flux to succinate to achieve an industrial process.

Results

Described here is the 2.3 MbA. succinogenesgenome sequence with emphasis onA. succinogenes's potential for genetic engineering, its metabolic attributes and capabilities, and its lack of pathogenicity. The genome sequence contains 1,690 DNA uptake signal sequence repeats and a nearly complete set of natural competence proteins, suggesting thatA. succinogenesis capable of natural transformation.A. succinogeneslacks a complete tricarboxylic acid cycle as well as a glyoxylate pathway, and it appears to be able to transport and degrade about twenty different carbohydrates. The genomes ofA. succinogenesand its closest known relative,Mannheimia succiniciproducens, were compared for the presence of known Pasteurellaceae virulence factors. Both species appear to lack the virulence traits of toxin production, sialic acid and choline incorporation into lipopolysaccharide, and utilization of hemoglobin and transferrin as iron sources. Perspectives are also given on the conservation ofA. succinogenesgenomic features in other sequenced Pasteurellaceae.

Conclusions

BothA. succinogenesandM. succiniciproducensgenome sequences lack many of the virulence genes used by their pathogenic Pasteurellaceae relatives. The lack of pathogenicity of these two succinogens is an exciting prospect, because comparisons with pathogenic Pasteurellaceae could lead to a better understanding of Pasteurellaceae virulence. The fact that theA. succinogenesgenome encodes uptake and degradation pathways for a variety of carbohydrates reflects the variety of carbohydrate substrates available in the rumen,A. succinogenes's natural habitat. It also suggests that many different carbon sources can be used as feedstock for succinate production byA. succinogenes.
"Pee-in-a-Pot": acceptability and uptake of on-site chlamydia screening in a student population in the Republic of Ireland
Authors: Vaughan Deirdre , O'Connell Emer , Cormican Martin , Brugha Ruairi , Faherty Colette , Balfe Myles , O'Donovan Diarmuid
Published: December 2010

Background

The aim of the study was to explore the acceptability and uptake of on-campus screening using a youth friendly approach in two Third Level higher education institutions (HEIs). This study is part of wider research exploring the optimal setting for chlamydia screening in Ireland.

Methods

Male and female students were given the opportunity to take a free anonymous test for chlamydia during a one week programme of "pee-in-a-pot" days at two HEI campuses in the West of Ireland. The study was set up after extensive consultation with the two HEIs and advertised on the two campuses using a variety of media in the two weeks preceding the screening days. Screening involved the provision and distribution of testing packs at communal areas and in toilet facilities. In Ireland, chlamydia notifications are highest amongst 20-29 year olds and hence the screening criterion was aimed at 18-29 year olds. Urine samples were tested using a nucleic acid amplification test (NAAT). Following the screening days, qualitative in-depth interviews were conducted with participants about their experiences of the event.

Results

Out of 1,249 test kits distributed in two HEIs, 592 specimens were collected giving a return rate of 47.5%. Tests excluded (54) were due to labelling errors or ineligibility of participants' age. Two thirds of those tested were females and the mean age was 21 years. Overall,3.9% (21/538) of participants tested positive, 5% (17/336) among females and 2% (4/191) among males. Participant interviews identified factors which enhanced student participation such as anonymity, convenience, accessibility of testing, and the informal and non-medical approach to testing.

Conclusions

Screening for chlamydia using on-campus "pee-in-a-pot" days is an acceptable strategy in this population. This model can detect and treat asymptomatic cases of chlamydia and avoid many of the barriers associated with testing for sexually transmitted infections (STIs) in clinical settings.
KRAS analysis in colorectal carcinoma: Analytical aspects of Pyrosequencing and allele-specific PCR in clinical practice
Authors: Sundström Magnus , Edlund Karolina , Lindell Monica , Glimelius Bengt , Birgisson Helgi , Micke Patrick , Botling Johan
Published: December 2010

Background

Epidermal growth factor receptor inhibitor therapy is now approved for treatment of metastatic colorectal carcinomas (CRC) in patients with tumors lacking KRAS mutations. Several procedures to detect KRAS mutations have been developed. However, the analytical sensitivity and specificity of these assays on routine clinical samples are not yet fully characterised.

Methods

The practical aspects and clinical applicability of a KRAS-assay based on Pyrosequencing were evaluated in a series of 314 consecutive CRC cases submitted for diagnostic KRAS analysis. The performance of Pyrosequencing compared to allele-specific, real-time PCR was then explored by a direct comparison of CE-IVD-marked versions of Pyrosequencing and TheraScreen (DxS) KRAS assays for a consecutive subset (n = 100) of the 314 clinical CRC samples.

Results

Using Pyrosequencing, 39% of the 314 CRC samples were found KRAS-mutated and several of the mutations (8%) were located in codon 61. To explore the analytical sensitivity of the Pyrosequencing assay, mutated patient DNA was serially diluted with wild-type patient DNA. Dilutions corresponding to 1.25-2.5% tumor cells still revealed detectable mutation signals. In clinical practice, our algorithm for KRAS analysis includes a reanalysis of samples with low tumor cell content (< 10%, n = 56) using an independent assay (allele-specific PCR, DxS). All mutations identified by Pyrosequencing were then confirmed and, in addition, one more mutated sample was identified in this subset of 56 samples. Finally, a direct comparison of the two technologies was done by re-analysis of a subset (n = 100) of the clinical samples using CE-IVD-marked versions of Pyrosequencing and TheraScreen KRAS assays in a single blinded fashion. The number of samples for which the KRAS codon 12/13 mutation status could be defined using the Pyrosequencing or the TheraScreen assay was 94 and 91, respectively, and both assays detected the same number of codon 12 and 13 mutations.

Conclusions

KRAS mutation detection using Pyrosequencing was evaluated on a consecutive set of clinical CRC samples. Pyrosequencing provided sufficient analytical sensitivity and specificity to assess the mutation status in routine formalin-fixed CRC samples, even in tissues with a low tumor cell content.
An assessment of early diagnosis and treatment of malaria by village health volunteers in the Lao PDR
Authors: Phommanivong Viengvaly , Thongkham Khanti , Deyer Gopinath , Rene Jean P , Barennes Hubert
Published: December 2010

Background

Early diagnosis and treatment (EDAT) is crucial to reducing the burden of malaria in low-income countries. In the Lao PDR, this strategy was introduced in 2004-2005 and an assessment was performed at the community level in January 2007.

Methods

EDAT with malaria rapid diagnostic test (MRDT) and artemisinin combination therapy (ACT) was prospectively assessed among 36 randomized village health volunteers (VHVs) and 720 patients in six malaria-endemic provinces of Laos (three pilot provinces (PP), and three non-pilots provinces (NPP)). ACT was also retrospectively assessed among 2188 patients within the same areas from June to November 2006. Two checklists were used and scores were calculated.

Results

EDAT performance of the VHVs was rated better in PP than in NPP (16.67% versus 38.89%, respectively, p = 0.004). Nearly all VHVs could diagnose malaria but only 16 (44%) could describe the symptoms of severe malaria. In January 2007, 31/720 (4%) patients tested positive using the Paracheck® test, 35 (5%) with microscopy (sensibility: 74.3%, specificity 99.3%, positive and negative predictive values: 83.9% and 98.7%, respectively). Patients from June to November were at higher risk of malaria: 35.19% of 2,188 febrile patients were positive (OR: 10.6, 95%CI: 7.4-15.5, p < 0.000). VHVs reported the MRDT easy to use, and yielded a satisfactory performance score. EDAT performance was rated as poor despite satisfactory results regarding ACT treatment, duration and dosages. Pre-referral treatment of severe malaria was infrequent and often inadequate, with 20% of these patients dying. Results suggest a higher mortality from severe malaria than officially reported. Shortage of ACT was frequent.

Discussion and conclusion

MRDT and ACT are useful and efficient and can be used by VHVs. VHVs' global EDAT performance is enhanced through training and monitoring. Persistent gaps in knowledge, care of patients and wrong treatment have to be addressed.
Dendritic cell subsets dynamics and cytokine production in SIVmac239-infected Chinese rhesus macaques
Authors: Xia Hou-Jun , Zhang Gao-Hong , Ma Jian-Ping , Dai Zheng-Xi , Li Shao-You , Han Jian-Bao , Zheng Yong-Tang
Published: December 2010

Background

Several studies have demonstrated that SIV infection progresses more slowly to experimental AIDS in Chinese rhesus macaques (Ch Rhs) than in Indian rhesus macaques (Ind Rhs). Here we investigated the dynamic and functional changes in dendritic cell (DC) subsets in SIVmac239-infected Ch Rhs.

Results

The numbers of both mDC and pDC strongly fluctuated but were not significantly changed during the acute and chronic phases of infection. However, the concentration of both poly (I:C)-induced IL-12 and HSV-1-induced IFN-α significantly increased in the acute phase of infection but returned to normal levels at the chronic phase of infection. The peak of IFN-α emerged earlier than that of IL-12, and it had a significantly positive correlation with IL-12, which indicated that IFN-α may initiate the immune activation. We also found that only the concentration of IFN-α was positively correlated with CD4+ T-cell counts, but it was negatively correlated with viral load.

Conclusion

High levels of IFN-α in the early stage of infection may contribute to effective control of virus replication, and normal levels of IFN-α during chronic infection may help Ch Rhs resist the disease progression. The change in DC subsets dynamics and cytokine production may help further our understanding of why Ch Rhs are able to live longer without progressing to an AIDS-like illness.
Involvement of Lysophosphatidic Acid in Bone Cancer Pain by Potentiation of TRPV1 via PKCe Pathway in Dorsal Root Ganglion Neurons
Authors: Pan Hai-Li , Zhang Yu-Qiu , Zhao Zhi-Qi
Published: December 2010

Background:

It has been demonstrated that lysophosphatidic acid (LPA) released from injury tissue and transient receptor potential vanilloid 1 (TRPV1) receptor are implicated in the induction of chronic pain. In the present study we examined whether an interaction between LPA receptor LPA1 and TRPV1 in dorsal root ganglion (DRG) neurons contributes to the development of bone cancer pain.

Results:

Bone cancer was established by injection of mammary gland carcinoma cells into the rat tibia. Following the development of bone cancer pain, the TRPV1 expression and capsaicin-evoked currents were up-regulated in rat DRG neurons at L4–6 segments. Immunohistochemistry staining revealed a high co-localization of LPA1 with TRPV1 in DRG neurons. In isolated DRG neurons, whole-cell patch recording showed that capsaicin-induced currents were potentiated by LPA in a dose-dependent manner. The potentiation was blocked by either LPA1 antagonist, protein kinase C (PKC) inhibitor or PKCε inhibitor, but not by protein kinase A (PKA) inhibitor or Rho inhibitor. In the behavioral tests, both mechanical allodynia and thermal hyperalgesia in bone cancer rats were attenuated by LPA1 antagonist.

Conclusion:

LPA potentiates TRPV1 current via a PKCe-dependent pathway in DRG neurons of rats with bone cancer, which may be a novel peripheral mechanism underlying the induction of bone cancer pain.
Thymic large cell neuroendocrine carcinoma: report of a resected case - a case report
Authors: Ogawa Fumihiro , Iyoda Akira , Amano Hideki , Nezu Kenji , Jiang Shi-Xu , Okayasu Isao , Satoh Yukitoshi
Published: December 2010

Thymic large cell neuroendocrine carcinomas (LCNECs) are very rare. We here describe a case in which the tumor could be completely resected. A 55-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor found at a regular health check-up. The patient underwent an extended thymectomy of an invasive thymoma of Masaoka's stage II that had been suspected preoperatively. The tumor was located in the right lobe of the thymus and was completely resected. Final pathological diagnosis of the surgical specimen was thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without recurrence or metastasis 16 months after surgery.
Presentation and management of keloid scarring following median sternotomy: a case study
Authors: Patel Rikesh , Papaspyros Sotiris C , Javangula Kalyana C , Nair Unnikrishnan
Published: December 2010

Introduction

Keloid scars following median sternotomy are rare and occur more frequently in pigmented skin. Different management strategies have been described with variable success. We present a case of keloid scar formation following cardiac surgery including our management and the final aesthetic result.

Case description

A 64 year old female of fair complexion underwent mitral valve replacement. The procedure and postoperative recovery were uncomplicated, however, during the following year, thick keloid scars formed over the incision sites. Initial non surgical measures failed to relieve pain and did not offer any tangible aesthetic benefit. Eventually surgical excision was attempted. She presented to our clinic for nine months follow up with significant improvement in pain and aesthetic result.

Discussion and Evaluation

Several theories have attempted to explore the pathophysiology of keloid scar formation. A number of predisposing factors have been documented however none existed in this case. A variety of invasive and non invasive approaches have been described but significant differences in success rates and methodology of investigations still precludes a standardized management protocol.

Conclusions

In this case study a rare presentation of keloid scar has been presented. The variety of methods used to improve pain and aesthetic result demonstrates the propensity of keloid scars to recur and the therapeutic challenges that surgeons have to face in their quest for a satisfactory patient outcome.
Developmental control of lateralized neuron size in the nematode Caenorhabditis elegans
Authors: Goldsmith Andrew D , Sarin Sumeet , Lockery Shawn , Hobert Oliver
Published: December 2010

Background

Nervous systems are generally bilaterally symmetric on a gross structural and organizational level but are strongly lateralized (left/right asymmetric) on a functional level. It has been previously noted that in vertebrate nervous systems, symmetrically positioned, bilateral groups of neurons in functionally lateralized brain regions differ in the size of their soma. The genetic mechanisms that control these left/right asymmetric soma size differences are unknown. The nematode Caenorhabditis elegans offers the opportunity to study this question with single neuron resolution. A pair of chemosensory neurons (ASEL and ASER), which are bilaterally symmetric on several levels (projections, synaptic connectivity, gene expression patterns), are functionally lateralized in that they express distinct chemoreceptors and sense distinct chemosensory cues.

Results

We describe here that ASEL and ASER also differ substantially in size (soma volume, axonal and dendritic diameter), a feature that is predicted to change the voltage conduction properties of the two sensory neurons. This difference in size is not dependent on sensory input or neuronal activity but developmentally programmed by a pathway of gene regulatory factors that also control left/right asymmetric chemoreceptor expression of the two ASE neurons. This regulatory pathway funnels via the DIE-1 Zn finger transcription factor into the left/right asymmetric distribution of nucleoli that contain the rRNA regulator Fibrillarin/FIB-1, a RNA methyltransferase implicated in the non-hereditary immune disease scleroderma, which we find to be essential to establish the size differences between ASEL and ASER.

Conclusions

Taken together, our findings reveal a remarkable conservation of the linkage of functional lateralization with size differences across phylogeny and provide the first insights into the developmentally programmed regulatory mechanisms that control neuron size lateralities.
Floral homeotic C function genes repress specific B function genes in the carpel whorl of the basal eudicot California poppy (Eschscholzia californica)
Authors: Yellina Aravinda L , Orashakova Svetlana , Lange Sabrina , Erdmann Robert , Leebens-Mack Jim , Becker Annette
Published: December 2010

Background

The floral homeotic C function gene AGAMOUS (AG) confers stamen and carpel identity and is involved in the regulation of floral meristem termination in Arabidopsis. Arabidopsis ag mutants show complete homeotic conversions of stamens into petals and carpels into sepals as well as indeterminacy of the floral meristem. Gene function analysis in model core eudicots and the monocots rice and maize suggest a conserved function for AG homologs in angiosperms. At the same time gene phylogenies reveal a complex history of gene duplications and repeated subfunctionalization of paralogs.

Results

EScaAG1 and EScaAG2, duplicate AG homologs in the basal eudicot Eschscholzia californica show a high degree of similarity in sequence and expression, although EScaAG2 expression is lower than EScaAG1 expression. Functional studies employing virus-induced gene silencing (VIGS) demonstrate that knock down of EScaAG1 and 2 function leads to homeotic conversion of stamens into petaloid structures and defects in floral meristem termination. However, carpels are transformed into petaloid organs rather than sepaloid structures. We also show that a reduction of EScaAG1 and EScaAG2 expression leads to significantly increased expression of a subset of floral homeotic B genes.

Conclusions

This work presents expression and functional analysis of the two basal eudicot AG homologs. The reduction of EScaAG1 and 2 functions results in the change of stamen to petal identity and a transformation of the central whorl organ identity from carpel into petal identity. Petal identity requires the presence of the floral homeotic B function and our results show that the expression of a subset of B function genes extends into the central whorl when the C function is reduced. We propose a model for the evolution of B function regulation by C function suggesting that the mode of B function gene regulation found in Eschscholzia is ancestral and the C-independent regulation as found in Arabidopsis is evolutionarily derived.
The Development of a Conceptual Framework and Tools to Assess Undergraduates' Principled Use of Models in Cellular Biology
Authors: Richmond Gail , Merritt Brett , Urban-Lurain Mark , Parker Joyce
Published: December 2010

Recent science education reform has been marked by a shift away from a focus on facts toward deep, rich, conceptual understanding. This requires assessment that also focuses on conceptual understanding rather than recall of facts. This study outlines our development of a new assessment framework and tool—a taxonomy— which, unlike existing frameworks and tools, is grounded firmly in a framework that considers the critical role that models play in science. It also provides instructors a resource for assessing students' ability to reason about models that are central to the organization of key scientific concepts. We describe preliminary data arising from the application of our tool to exam questions used by instructors of a large-enrollment cell and molecular biology course over a 5-yr period during which time our framework and the assessment tool were increasingly used. Students were increasingly able to describe and manipulate models of the processes and systems being studied in this course as measured by assessment items. However, their ability to apply these models in new contexts did not improve. Finally, we discuss the implications of our results and the future directions for our research.
Integration of Information and Scientific Literacy: Promoting Literacy in Undergraduates
Authors: Porter Jason A. , Wolbach Kevin C. , Purzycki Catherine B. , Bowman Leslie A. , Agbada Eva , Mostrom Alison M.
Published: December 2010

The Association of College and Research Libraries recommends incorporating information literacy (IL) skills across university and college curricula, for the goal of developing information literate graduates. Congruent with this goal, the Departments of Biological Sciences and Information Science developed an integrated IL and scientific literacy (SL) exercise for use in a first-year biology course. Students were provided the opportunity to access, retrieve, analyze, and evaluate primary scientific literature. By the completion of this project, student responses improved concerning knowledge and relevance of IL and SL skills. This project exposes students to IL and SL early in their undergraduate experience, preparing them for future academic advancement.
Thinking about the Conceptual Foundations of the Biological Sciences
Authors: Klymkowsky M. W.
Published: December 2010

Not until the core concepts of biology are clearly defined and become the focus of instruction and assessment can we expect meaningful improvements in biological literacy and the removal of unnecessary barriers to student engagement.
Cell death, it always matters
Authors: Comalada Mònica , Serrat Neus , Xaus Jordi
Published: December 2010

Cautionary note against underestimating death, since it has an impact both in vitro and, obviously, in in vivo studies.
Dead cells certainly do matter, particularly when they can speak from the grave
Authors: Sweet Matthew J
Published: December 2010

Response letter to discussion on pro- and anti-inflammatory effects of HDAC inhibitors on macrophage inflammatory responses and cell death.
Sociocultural practices in Ethiopia: association with onset and persistence of postnatal common mental disorders
Authors: Hanlon Charlotte , Medhin Girmay , Alem Atalay , Araya Mesfin , Abdulahi Abdulreshid , Tomlinson Mark , Hughes Marcus , Patel Vikram , Dewey Michael , Prince Martin
Published: December 2010

Background

Traditional perinatal practices may protect against postnatal common mental disorders (CMD) in non-Western societies.

Aims

To evaluate the association between perinatal practices and postnatal CMD in rural Ethiopia.

Method

A population-based sample of 1065 women was followed up from pregnancy until 2 months postpartum. Qualitative investigation informed the development of scales measuring attitudes towards and adherence to perinatal practices. Postnatal CMD was measured using the Self-Reporting Questionnaire.

Results

Endorsement of sociocultural perinatal practices was associated with lower odds of antenatal CMD persisting into the postnatal period (adjusted odds ratio (OR) = 0.66, 95% CI 0.45–0.95). Women who endorsed protective and celebratory perinatal practices but were unable to complete them had increased odds of incident (adjusted OR = 7.26, 95% CI 1.38–38.04) and persistent postnatal CMD (adjusted OR = 2.16, 95% CI 1.11–4.23) respectively.

Conclusions

There is evidence for an independent role of sociocultural practices in maintaining perinatal mental health in this Ethiopian community.
Effectiveness of reminders in reducing non-attendance among out-patients
Authors: Rajasuriya Mahesh , de Silva Varuni , Hanwella Raveen
Published: December 2010

Aims and method

Non-attendance rates in a psychiatric out-patient clinic and the effectiveness of telephone or postal reminders in reducing non-attendance were evaluated. All patients who did not attend the clinic for their second appointment within 2 weeks were contacted by telephone or letter. Patients who failed to attend the clinic 6 weeks after the reminder were classified as non-attendees.

Results

Rate of non-attendance before the intervention was 31.3% (n = 61/195). After the intervention this was reduced to 23.1%, a relative risk reduction of 26.2%. Being male, not being prescribed medicines, having a diagnosis of psychoactive substance use or dementia were risk factors for non-attendance (odds ratio, OR>1). Risk of non-attendance was low for bipolar disorder, schizophrenia and depressive disorder (OR <1).

Clinical implications

A simple low-cost intervention in the form of a reminder reduced non-attendance rates. Routine implementation of this intervention should be considered in all psychiatry out-patient services in low- and middle-income countries.
Media Framing and Political Advertising in the Patients' Bill of Rights Debate
Authors: Rabinowitz Aaron
Published: December 2010

The purpose of this article is to assess the influence of interest groups over news content. In particular, I explore the possibility that political advertising campaigns affect the tenor and framing of newspaper coverage in health policy debates. To do so, I compare newspaper coverage of the Patients' Bill of Rights debate in 1999 in five states that were subject to extensive advertising campaigns with coverage in five comparison states that were not directly exposed to the advocacy campaigns. I find significant differences in coverage depending on the presence or absence of paid advertising campaigns, and conclude that readers were exposed to different perspectives and arguments about managed care regulation if the newspapers they read were published in states targeted by political advertisements. Specifically, newspaper coverage was 17 percent less likely to be supportive of managed care reform in states subject to advertising campaigns designed to foment opposition to the Patients' Bill of Rights. Understanding the ability of organized interests and political actors to successfully promote their preferred issue frames in a dynamic political environment is particularly important in light of the proliferation of interest groups, the prevalence of multimillion-dollar political advertising campaigns, and the health care reform debate under President Barack Obama.
Interest-Based Mediation of Medical Malpractice Lawsuits: A Route to Improved Patient Safety?
Authors: Hyman Chris Stern , Liebman Carol B. , Schechter Clyde B. , Sage William M.
Published: December 2010

Mediation of medical malpractice lawsuits provides savings for the parties by shortening the litigation process. In theory, information that aids emotional healing and improves patient care can also surface through mediation. The study discussed in this article used structured interviews of participants and mediators in thirty-one mediated malpractice lawsuits involving eleven nonprofit hospitals. The study measured perceptions of the process and mediation's effects on settlement, expenses, apology, satisfaction, and information exchange. Defense lawyers were less likely than plaintiff attorneys to mediate. Both plaintiff and defense attorneys were satisfied with the process, as were plaintiffs, hospital representatives, and insurers. Changes in hospitals' practices or policies to improve patient safety were identified. This study demonstrates that major challenges stand in the way of achieving mediation's full benefits. Absence of physician participation minimizes the chances that mediated discussion of adverse events and medical errors can lead to improved quality of care. Change will require medical leaders, hospital administrators, and malpractice insurers to temper their suspicion of the tort system sufficiently to approach medical errors and adverse events as learning opportunities, and to retain lawyers who embrace mediation as an opportunity to solve problems, show compassion, and improve care.
G-protein-coupled receptor heteromer dynamics
Authors: Vilardaga Jean-Pierre , Agnati Luigi F. , Fuxe Kjell , Ciruela Francisco
Published: December 2010

G-protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors, and have evolved to detect and transmit a large palette of extracellular chemical and sensory signals into cells. Activated receptors catalyze the activation of heterotrimeric G proteins, which modulate the propagation of second messenger molecules and the activity of ion channels. Classically thought to signal as monomers, different GPCRs often pair up with each other as homo- and heterodimers, which have been shown to modulate signaling to G proteins. Here, we discuss recent advances in GPCR heteromer systems involving the kinetics of the early steps in GPCR signal transduction, the dynamic property of receptor–receptor interactions, and how the formation of receptor heteromers modulate the kinetics of G-protein signaling.
DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion
Authors: Rodier Francis , Muñoz Denise P. , Teachenor Robert , Chu Victoria , Le Oanh , Bhaumik Dipa , Coppé Jean-Philippe , Campeau Eric , Beauséjour Christian M. , Kim Sahn-Ho , Davalos Albert R. , Campisi Judith
Published: December 2010

DNA damage can induce a tumor suppressive response termed cellular senescence. Damaged senescent cells permanently arrest growth, secrete inflammatory cytokines and other proteins and harbor persistent nuclear foci that contain DNA damage response (DDR) proteins. To understand how persistent damage foci differ from transient foci that mark repairable DNA lesions, we identify sequential events that differentiate transient foci from persistent foci, which we term ‘DNA segments with chromatin alterations reinforcing senescence’ (DNA-SCARS). Unlike transient foci, DNA-SCARS associate with PML nuclear bodies, lack the DNA repair proteins RPA and RAD51, lack single-stranded DNA and DNA synthesis and accumulate activated forms of the DDR mediators CHK2 and p53. DNA-SCARS form independently of p53, pRB and several other checkpoint and repair proteins but require p53 and pRb to trigger the senescence growth arrest. Importantly, depletion of the DNA-SCARS-stabilizing component histone H2AX did not deplete 53BP1 from DNA-SCARS but diminished the presence of MDC1 and activated CHK2. Furthermore, depletion of H2AX reduced both the p53-dependent senescence growth arrest and p53-independent cytokine secretion. DNA-SCARS were also observed following severe damage to multiple human cell types and mouse tissues, suggesting that they can be used in combination with other markers to identify senescent cells. Thus, DNA-SCARS are dynamically formed distinct structures that functionally regulate multiple aspects of the senescent phenotype.
Micropatterning as a tool to decipher cell morphogenesis and functions
Authors: Théry Manuel
Published: December 2010

In situ, cells are highly sensitive to geometrical and mechanical constraints from their microenvironment. These parameters are, however, uncontrolled under classic culture conditions, which are thus highly artefactual. Micro-engineering techniques provide tools to modify the chemical properties of cell culture substrates at sub-cellular scales. These can be used to restrict the location and shape of the substrate regions, in which cells can attach, so-called micropatterns. Recent progress in micropatterning techniques has enabled the control of most of the crucial parameters of the cell microenvironment. Engineered micropatterns can provide a micrometer-scale, soft, 3-dimensional, complex and dynamic microenvironment for individual cells or for multi-cellular arrangements. Although artificial, micropatterned substrates allow the reconstitution of physiological in situ conditions for controlled in vitro cell culture and have been used to reveal fundamental cell morphogenetic processes as highlighted in this review. By manipulating micropattern shapes, cells were shown to precisely adapt their cytoskeleton architecture to the geometry of their microenvironment. Remodelling of actin and microtubule networks participates in the adaptation of the entire cell polarity with respect to external constraints. These modifications further impact cell migration, growth and differentiation.
Power, Status, and Learning in Organizations
Authors: Bunderson J. Stuart , Reagans Ray E.
Published: December 2010

This paper reviews the scholarly literature on the effects of social hierarchy—differences in power and status among organizational actors—on collective learning in organizations and groups. We begin with the observation that theories of organization and group learning have tended to adopt a rational system model, a model that emphasizes goal-directed and cooperative interactions between and among actors who may differ in knowledge and expertise but are undifferentiated with respect to power and status. Our review of the theoretical and empirical literatures on power, status, and learning suggests that social hierarchy can complicate a rational system model of collective learning by disrupting three critical learning-related processes: anchoring on shared goals, risk taking and experimentation, and knowledge sharing. We also find evidence to suggest that the stifling effects of power and status differences on collective learning can be mitigated when advantaged actors are collectively oriented. Indeed, our review suggests that higher-ranking actors who use their power and status in more “socialized” ways can play critical roles in stimulating collective learning behavior. We conclude by articulating several promising directions for future research that were suggested by our review.
On the Narrative Construction of Multinational Corporations: An Antenarrative Analysis of Legitimation and Resistance in a Cross-Border Merger
Authors: Vaara Eero , Tienari Janne
Published: December 2010

Although extant research has highlighted the role of discourse in the cultural construction of organizations, there is a need to elucidate the use of narratives as central discursive resources in unfolding organizational change. Hence, the objective of this article is to develop a new kind of antenarrative approach for the cultural analysis of organizational change. We use merging multinational corporations (MNCs) as a case in point. Our empirical analysis focuses on a revelatory case: the financial services group Nordea, which was built by combining Swedish, Finnish, Danish, and Norwegian corporations. We distinguish three types of antenarrative that provided alternatives for making sense of the merger: globalist, nationalist, and regionalist (Nordic) antenarratives. We focus on how these antenarratives were mobilized in intentional organizational storytelling to legitimate or resist change: globalist storytelling as a means to legitimate the merger and to create MNC identity, nationalist storytelling to relegitimate national identities and interests, Nordic storytelling to create regional identity, and the critical use of the globalist storytelling to challenge the Nordic identity. We conclude that organizational storytelling is characterized by polyphonic, stylistic, chronotopic, and architectonic dialogisms and by a dynamic between centering and decentering forces. This paper contributes to discourse-cultural studies of organizations by explaining how narrative constructions of identities and interests are used to legitimate or resist change. Furthermore, this analysis elucidates the dialogical dynamics of organizational storytelling and thereby opens up new avenues for the cultural analysis of organizations.
What happens to femoral neck bone mineral density after hip resurfacing surgery?
Authors: Cordingley R. , Kohan L. , Ben-Nissan B.
Published: December 2010

The major advantage of hip resurfacing is the decreased amount of bone resection compared with a standard total hip replacement. Fracture of the femoral neck is the most common early complication and poor bone quality is a major risk factor. We undertook a prospective consecutive case control study examining the effect of bone mineral density changes in patients undergoing hip resurfacing surgery. A total of 423 patients were recruited with a mean age of 54 years (24 to 87). Recruitment for this study was dependent on pre-operative bilateral femoral bone mineral density results not being osteoporotic. The operated and non-operated hips were assessed. Bone mineral density studies were repeated over a two-year period. The results showed no significant deterioration in the bone mineral density in the superolateral region in the femoral neck, during that period.

These findings were in the presence of a markedly increased level of physical activity, as measured by the short-form 36 health survey physical function score.
The use of osteo-articular allografts for reconstruction after resection of the distal radius for tumour
Authors: Scoccianti G. , Campanacci D. A. , Beltrami G. , Caldora P. , Capanna R.
Published: December 2010

Several techniques have been described to reconstruct a mobile wrist joint after resection of the distal radius for tumour. We reviewed our experience of using an osteo-articular allograft to do this in 17 patients with a mean follow-up of 58.9 months (28 to 119).

The mean range of movement at the wrist was 56° flexion, 58° extension, 84° supination and 80° pronation. The mean ISOLS-MSTS score was 86% (63% to 97%) and the mean patient-rated wrist evaluation score was 16.5 (3 to 34). There was no local recurrence or distant metastases. The procedure failed in one patient with a fracture of the graft and an arthrodesis was finally required. Union was achieved at the host-graft interface in all except two cases. No patient reported more than modest non-disabling pain and six reported no pain at all. Radiographs showed early degenerative changes at the radiocarpal joint in every patient.

A functional pain-free wrist can be restored with an osteo-articular allograft after resection of the distal radius for bone tumour, thereby avoiding the donor site morbidity associated with an autograft. These results may deteriorate with time.
Simultaneous bilateral versus unilateral total ankle replacement
Authors: Barg A. , Knupp M. , Hintermann B.
Published: December 2010

The aim of this study was to compare the outcome of bilateral sequential total ankle replacement (TAR) with that of unilateral TAR. We reviewed 23 patients who had undergone sequential bilateral TAR under a single anaesthetic and 46 matched patients with a unilateral TAR. There were no significant pre-operative differences between the two groups in terms of age, gender, body mass index, American Society of Anaesthesiologists classification and aetiology of the osteoarthritis of the ankle. Clinical and radiological follow-up was carried out at four months, one and two years.

After four months, patients with simultaneous bilateral TAR reported a significantly higher mean pain score than those with a unilateral TAR. The mean American Orthopaedic Foot and Ankle Society hindfoot score and short-form 36 physical component summary score were better in the unilateral group. However, this difference disappeared at the one-and two-year follow-ups.

Bilateral sequential TAR under one anaesthetic can be offered to patients with bilateral severe ankle osteoarthritis. However, they should be informed of the long recovery period.
The Role of Benzalkonium Chloride in the Occurrence of Punctate Keratitis: A Meta-Analysis of Randomized, Controlled Clinical Trials
Authors: Trocme Stefan , Hwang Lie-Ju , Bean Gerald W , Sultan Maria B
Published: December 2010

Background:

Benzalkonium chloride (BAK), the most commonly used preservative in topical ophthalmic solutions, has undergone considerable criticism in recent years, principally based on in vitro and in vivo studies. Relevance to the clinical setting has not been confirmed.

Objective:

To determine whether administration of twice the amount of BAK was associated with an increased incidence of punctate keratitis in long-term, double-masked trials comparing latanoprost ophthalmic solution and vehicle with timolol ophthalmic solution in patients with glaucoma or ocular hypertension.

Methods:

A meta-analysis of the double-masked phases of 7 prospective, controlled clinical trials compared the incidence of punctate keratitis among patients assigned to treatment with latanoprost or timolol. In all studies, the amount of BAK administered daily in the latanoprost arms was approximately twice the amount used in the timolol arms. All reports of punctate keratitis either as a finding or an adverse event were included. A fixed-effect model was used because the heterogeneity was small and not statistically significant. Sensitivity analyses were conducted. Funnel plots were provided to address potential publication bias.

Results:

Of the 1694 patients enrolled in the double-masked portion of the trials (latanoprost, n = 892; timolol, n = 802), the overall incidence of punctate keratitis was 6.3% (106/1694). The incidence in latanoprost-treated patients was 6.5% and in timolol-treated patients was 6.0%. The risk difference for punctate keratitis of latanoprost versus timolol was 0.005 (95% CI –0.011 to 0.020; p = 0.574), and the risk ratio of latanoprost versus timolol was 1.084 (95% CI 0.739 to 1.589; p = 0.680).

Conclusions:

These results indicate that BAK does not produce significant corneal toxicity in the vast majority of patients with glaucoma or ocular hypertension at the concentrations used in these studies.
A Pharmaceutical Care Program to Improve Adherence to Statin Therapy: A Randomized Controlled Trial
Authors: Eussen Simone RBM , Elst Menno E van der , Klungel Olaf H , Rompelberg Cathy JM , Garssen Johan , Oosterveld Marco H , Boer Anthonius de , Gier Johan J de , Bouvy Marcel L
Published: December 2010

Background:

Despite the well-known beneficial effects of statins, many patients do not adhere to chronic medication regimens.

Objective:

To implement and assess the effectiveness of a community pharmacy-based pharmaceutical care program developed to improve patients' adherence to statin therapy.

Methods:

An open-label, prospective, randomized controlled trial was conducted at 26 community pharmacies in the Netherlands. New users of statins who were aged 18 years or older were randomly assigned to receive either usual care or a pharmacist intervention. The intervention consisted of 5 individual counseling sessions by a pharmacist during a 1-year period. During these sessions, patients received structured education about the importance of medication adherence, lipid levels were measured, and the association between adherence and lipid levels was discussed. Adherence to statin therapy was assessed as discontinuation rates 6 and 12 months after statin initiation, and as the medication possession ratio (MPR), and compared between the pharmaceutical care and usual care groups.

Results:

A total of 899 subjects (439 in the pharmaceutical care group and 460 in the usual care group) were evaluable for effectiveness analysis. The pharmaceutical care program resulted in a significantly lower rate of discontinuation within 6 months after initiating therapy versus usual care (HR 0.66, 95% CI 0.46 to 0.96). No significant difference between groups was found in discontinuation at 12 months (HR 0.84, 95% CI 0.65 to 1.10). Median MPR was very high (>99%) in both groups and did not differ between groups.

Conclusions:

These results demonstrate the feasibility and effectiveness of a community pharmacy–based pharmaceutical care program to improve medication adherence in new users of statins. Frequent counseling sessions (every 3 months) are necessary to maintain the positive effects on discontinuation. Although improvements are modest, the program can be applied easily to a larger population and have a large impact, as the interventions are relatively inexpensive and easy to implement in clinical practice.
Unintentional Therapeutic Errors Involving Insulin in the Ambulatory Setting Reported to Poison Centers
Authors: Spiller Henry A , Borys Douglas J , Ryan Mark L , Sawyer Tama S , Wilson Brooke L
Published: December 2010

Background

Adverse drug events in the ambulatory care setting are not uncommon and can cause significant morbidity. Little research has been published on the management of adverse drug events involving insulin in the outpatient setting.

Objective

To analyze data on patients with unintentional therapeutic errors involving insulin managed by 9 regional poison control centers.

Methods

A retrospective search was performed for all records involving insulin at 9 poison centers, covering the population of 4 states for the years 2000–2009. A subgroup of the study population was selected with a reason for exposure of “unintentional–therapeutic error.”

Results:

There were 3819 insulin exposures reported, with an increase in the annual incidence of insulin exposures of 279% (from 170 to 645 patients/year) and a mean annual increase of 16%. Of the insulin exposures, 2584 were unintentional therapeutic errors (68%). The percentage of all insulin exposures that were unintentional therapeutic errors increased progressively, from 41% to 78%. There was a 495% increase in annual incidence of unintentional therapeutic errors involving insulin, with a mean annual increase of 26%. Unintentional therapeutic errors involving insulin occurred primarily in adults >40 years (73%), with 63% occurring in women. There was a pronounced increase in unintentional therapeutic errors involving insulin in the later evening hours, with 71% occurring between 1800 and 2400 and reaching a peak at 2200. The majority (n = 1803; 70%) of patients were managed in a non–health-care facility location, primarily their own residence.

Conclusions:

This is the first report of an increasing trend of insulin-related unintentional therapeutic errors in the ambulatory setting. Our study highlights a number of striking features, including: (1) a consistent and dramatic increase of unintentional therapeutic errors involving insulin over the 10-year period, (2) a high incidence of unintentional therapeutic errors involving insulin in the late evening hours, and (3) a high incidence of unintentional therapeutic errors involving insulin involving adults >40 years and females. With their 24/7 availability, poison centers appear to be an increasingly important resource for patients experiencing unintentional therapeutic errors involving insulin.