Warfarin use in the elderly: The nurses' perspective

Objective: To explore the barriers to warfarin use from the perspective of nurses working in aged care. Design: A qualitative study, involving a semi-structured group interview, during March-April 2001. Setting and Subjects: Eleven nurses, employed within the catchment of the Northern Sydney Area Health Service, who were involved in the care of elderly warfarinised patients. Main outcome measure: Identification, via thematic analysis, of the main themes underpinning the nursing perspective on warfarin use in this setting, with regard to their perceived role/s, experiences with patients, and potential strategies for managing the therapy. Results: Five main themes were identified: perceived patient attitude toward warfarin; barriers to the use of warfarin; expressed lack of confidence in the processes involved; nurses' role in warfarin use; and strategies to improve warfarin use. Nurses were concerned about warfarin use in the elderly, but felt they had a limited capacity to intervene. Conclusion: Nurses are potentially underutilised as a resource and support for both patients and prescribers, in the management of warfarin therapy

Balancing risk versus benefit: The elderly patient's perspective on warfarin therapy

Warfarin theraphy is underused in the target at-risk elderly population. Clinicians perceive that older patients are reluctant to use this theraphy, however the perspective of patients or their carers has yet to be explored. Objective: To explore in-depth the perspectives of elderly patients and/ or their carers regarding the use of warfarin therapy. Method: A qualitative study, using semi-structured group interviews was undertaken. The audio-taped discussions were transcribed verbatim, then thematically analysed to identify emergent themes. Group discussions were conducted at a major Sydney teaching hospital, over a 2-month period. Individuals aged 65 years or older (and/or their carers) who were using long-term (6 months) warfarin therapy were recruited by voluntary response to study flyers. Results: 17 patients and carers (mean age 77.2 SD=7.5 years) participated in one of two focus groups. Five core themes emerged regarding warfarin therapy: inadequate knowledge and understanding about it, patients/carers variable experience of information provision, cycle of reactions to being on it, issues in its practical management, and the spectrum of experiences with it. Overall, participants were very accepting of the therapy, describing a high level of compliance, despite initial fears and anxieties, and a relative lack of knowledge. Patients felt somewhat abandoned in their management of warfarin due to the lack of ongoing support services in the community, and inadequate information provision. Conclusions: Elderly patients and their carers appear to be quite accepting of warfarin therapy, in contrast to the perceptions of health care professionals. More effort is needed, however, in terms of information provision, particularly in the form of community-based services, to assist patients in the long-term management of warfarin

Management of warfarin in atrial fibrillation: Views of health professionals, older patients and their carers

Objective: To identify the views of health professionals, patients and their carers on strategies to improve the use and management of warfarin in older patients with atrial fibrillation. Design: Qualitative study based on analysis of group interviews. Setting: A major metropolitan teaching hospital, from 1 March to 30 April 2003. Participants: 14 patients (≥ 65 years) with established atrial fibrillation and taking warfarin, three carers, 12 specialists, eight general practitioners, six community pharmacists, nine hospital pharmacists, and 11 nurses volunteered in response to flyers promoting the study. Results: Suggested strategies to improve warfarin management targeted support services for GPs and patients. Hospital-based clinicians felt that dissemination of trial evidence to GPs to support treatment recommendations is required, and that GPs need to enlist allied health professionals in the management of patients taking warfarin. GPs preferred access to practical advice from expert colleagues on the day-to-day management. Patients requested more information about warfarin therapy, as access to information is inadequate, particularly from primary sources (GPs, community pharmacists). Verbal and written information are equally important, but a single counselling session or supply of a booklet was viewed as inadequate. Participants identified various interventions for all levels of warfarin management; from the collective input, a framework for management strategies was developed. Conclusions: Health professionals and patients require more customised information to support warfarin use and management

Current and Calcium Responses to Local Activation of Axonal NMDA Receptors in Developing Cerebellar Molecular Layer Interneurons

In developing cerebellar molecular layer interneurons (MLIs), NMDA increases spontaneous GABA release. This effect had been attributed to either direct activation of presynaptic NMDA receptors (preNMDARs) or an indirect pathway involving activation of somato-dendritic NMDARs followed by passive spread of somatic depolarization along the axon and activation of axonal voltage dependent Ca2+ channels (VDCCs). Using Ca2+ imaging and electrophysiology, we searched for preNMDARs by uncaging NMDAR agonists either broadly throughout the whole field or locally at specific axonal locations. Releasing either NMDA or glutamate in the presence of NBQX using short laser pulses elicited current transients that were highly sensitive to the location of the spot and restricted to a small number of varicosities. The signal was abolished in the presence of high Mg2+ or by the addition of APV. Similar paradigms yielded restricted Ca2+ transients in interneurons loaded with a Ca2+ indicator. We found that the synaptic effects of NMDA were not inhibited by blocking VDCCs but were impaired in the presence of the ryanodine receptor antagonist dantrolene. Furthermore, in voltage clamped cells, bath applied NMDA triggers Ca2+ elevations and induces neurotransmitter release in the axonal compartment. Our results suggest the existence of preNMDARs in developing MLIs and propose their involvement in the NMDA-evoked increase in GABA release by triggering a Ca2+-induced Ca2+ release process mediated by presynaptic Ca2+ stores. Such a mechanism is likely to exert a crucial role in various forms of Ca2+-mediated synaptic plasticity

Establishing an infrastructure for collaboration in primate cognition research

Inferring the evolutionary history of cognitive abilities requires large and diverse samples. However, such samples are often beyond the reach of individual researchers or institutions, and studies are often limited to small numbers of species. Consequently, methodological and site-specific-differences across studies can limit comparisons between species. Here we introduce the ManyPrimates project, which addresses these challenges by providing a large-scale collaborative framework for comparative studies in primate cognition. To demonstrate the viability of the project we conducted a case study of short-term memory. In this initial study, we were able to include 176 individuals from 12 primate species housed at 11 sites across Africa, Asia, North America and Europe. All subjects were tested in a delayed-response task using consistent methodology across sites. Individuals could access food rewards by remembering the position of the hidden reward after a 0, 15, or 30-second delay. Overall, individuals performed better with shorter delays, as predicted by previous studies. Phylogenetic analysis revealed a strong phylogenetic signal for short-term memory. Although, with only 12 species, the validity of this analysis is limited, our initial results demonstrate the feasibility of a large, collaborative open-science project. We present the ManyPrimates project as an exciting opportunity to address open questions in primate cognition and behaviour with large, diverse datasets

Up-Regulation of MUC2 and IL-1β Expression in Human Colonic Epithelial Cells by Shigella and Its Interaction with Mucins

BACKGROUND: The entire gastrointestinal tract is protected by a mucous layer, which contains complex glycoproteins called mucins. MUC2 is one such mucin that protects the colonic mucosa from invading microbes. The initial interaction between microbes and mucins is an important step for microbial pathogenesis. Hence, it was of interest to investigate the relationship between host (mucin) and pathogen interaction, including Shigella induced expression of MUC2 and IL-1β during shigellosis. METHODS: The mucin-Shigella interaction was revealed by an in vitro mucin-binding assay. Invasion of Shigella dysenteriae into HT-29 cells was analyzed by Transmission electron microscopy. Shigella induced mucin and IL-1β expression were analyzed by RT-PCR and Immunofluorescence. RESULTS: The clinical isolates of Shigella were found to be virulent by a congo-red binding assay. The in vitro mucin-binding assay revealed both Shigella dysenteriae and Shigella flexneri have binding affinity in the increasing order of: guinea pig small intestinal mucin<guinea pig colonic mucin< Human colonic mucin. Invasion of Shigella dysenteriae into HT-29 cells occurs within 2 hours. Interestingly, in Shigella dysenteriae infected conditions, significant increases in mRNA expression of MUC2 and IL-1β were observed in a time dependent manner. Further, immunofluorescence analysis of MUC2 shows more positive cells in Shigella dysenteriae treated cells than untreated cells. CONCLUSIONS: Our study concludes that the Shigella species specifically binds to guinea pig colonic mucin, but not to guinea pig small intestinal mucin. The guinea pig colonic mucin showed a greater binding parameter (R), and more saturable binding, suggesting the presence of a finite number of receptor binding sites in the colonic mucin of the host. In addition, modification of mucins with TFMS and sodium metaperiodate significantly reduced mucin-bacterial binding; suggesting that the mucin-Shigella interaction occurs through carbohydrate epitopes on the mucin backbones. Overproduction of MUC2 may alter adherence and invasion of Shigella dysenteriae into human colonic epithelial cells

The Web will kill them all: new media, digital utopia, and political struggle in the Italian 5-Star Movement

This article examines the role of discourses about new media technology and the Web in the rise of the 5-Star Movement (Movimento 5 Stelle, or M5S) in Italy. Founded by comedian and activist Beppe Grillo and Web entrepreneur Gianrobe rto Casaleggio in 2009, this movement succeeded in becoming the second largest party at t he 2013 national elections in Italy. This article aims to discuss how elements of digital uto pia and Web-centric discourses have been inserted into the movement’s political message, and how the construction of the Web as a myth has shaped the movement’s discourse and political p ractice. The 5-Star Movement is compared and contrasted with other social and political move ments in Western countries which have displayed a similar emphasis on new media, such as the Occupy movement, the Indignados movement, and the Pirate Parties in Sweden and Germ any. By adopting and mutating cyber- utopian discourses from the so-called Californian i deology, the movement symbolically identifies itself with the Web. The traditional political esta blishment is associated with “old” media (television, radio, and the printed press), and rep resented as a “walking dead,” doomed to be superseded and buried by a Web-based direct democra cy

Bacteria-Induced Uroplakin Signaling Mediates Bladder Response to Infection

Urinary tract infections are the second most common infectious disease in humans and are predominantly caused by uropathogenic E. coli (UPEC). A majority of UPEC isolates express the type 1 pilus adhesin, FimH, and cell culture and murine studies demonstrate that FimH is involved in invasion and apoptosis of urothelial cells. FimH initiates bladder pathology by binding to the uroplakin receptor complex, but the subsequent events mediating pathogenesis have not been fully characterized. We report a hitherto undiscovered signaling role for the UPIIIa protein, the only major uroplakin with a potential cytoplasmic signaling domain, in bacterial invasion and apoptosis. In response to FimH adhesin binding, the UPIIIa cytoplasmic tail undergoes phosphorylation on a specific threonine residue by casein kinase II, followed by an elevation of intracellular calcium. Pharmacological inhibition of these signaling events abrogates bacterial invasion and urothelial apoptosis in vitro and in vivo. Our studies suggest that bacteria-induced UPIIIa signaling is a critical mediator of bladder responses to insult by uropathogenic E. coli

Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

<p>Abstract</p> <p>Background</p> <p>Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (<it>DPYD</it>).</p> <p>Methods</p> <p>In this study, we evaluated <it>DPYD </it>promoter methylation through quantitative methylation-specific PCR and screened <it>DPYD </it>for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. <it>DPYD </it>promoter methylation was also assessed in tumor tissue from 29 patients</p> <p>Results</p> <p>Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, <it>DPYD </it>promoter methylation and large <it>DPYD </it>intragenic rearrangements were absent in all cases analyzed.</p> <p>Conclusions</p> <p>Our results indicate that <it>DPYD </it>promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.</p

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT