Remote working: survey of attitudes to eHealth of doctors and nurses in rural general practices in the United Kingdom.

BACKGROUND: Health professionals in rural primary care could gain more from eHealth initiatives than their urban counterparts, yet little is known about eHealth in geographically isolated areas of the UK. OBJECTIVE: To elicit current use of, and attitudes towards eHealth of professionals in primary care in remote areas of Scotland. METHODS: In 2002, a questionnaire was sent to all general practitioners (n=154) in Scotland's 82 inducement practices, and to 67 nurses. Outcome measures included reported experience of computer use; access to, and experience of eHealth and quality of that experience; views of the potential usefulness of eHealth and perceived barriers to the uptake of eHealth. RESULTS: Response rate was 87%. Ninety-five percent of respondents had used either the Internet or email. The proportions of respondents who reported access to ISDN line, scanner, digital camera, and videoconferencing unit were 71%, 48%, 40% and 36%, respectively. Use of eHealth was lower among nurses than GPs. Aspects of experience that were rated positively were 'clinical usefulness', 'functioning of equipment' and 'ease of use of equipment' (76%, 74%, and 74%, respectively). The most important barriers were 'lack of suitable training' (55%), 'high cost of buying telemedicine equipment' (54%), and 'increase in GP/nurse workload' (43%). Professionals were concerned about the impact of tele-consulting on patient privacy and on the consultation itself. CONCLUSIONS: Although primary healthcare professionals recognize the general benefits of eHealth, uptake is low. By acknowledging barriers to the uptake of eHealth in geographically isolated settings, broader policies on its implementation in primary care may be informed

Molecular Mechanisms for Drug Hypersensitivity Induced by the Malaria Parasite's Chloroquine Resistance Transporter

Mutations in the Plasmodium falciparum ‘chloroquine resistance transporter’ (PfCRT) confer resistance to chloroquine (CQ) and related antimalarials by enabling the protein to transportthese drugs away from their targets within the parasite’s digestive vacuole (DV). However, CQ resistance-conferring isoforms of PfCRT (PfCRTCQR) also render the parasite hypersensitive to a subset of structurally-diverse pharmacons. Moreover, mutations in PfCRTCQR that suppress the parasite’s hypersensitivity to these molecules simultaneously reinstate its sensitivity to CQ and related drugs. We sought to understand these phenomena by characterizing the functions of PfCRTCQR isoforms that cause the parasite to become hypersensitive to the antimalarial quinine or the antiviral amantadine. We achieved this by measuring the abilities of these proteins to transport CQ, quinine, and amantadine when expressed in Xenopus oocytes and complemented this work with assays that detect the drug transport activity of PfCRT in its native environment within the parasite. Here we describe two mechanistic explanations for PfCRT-induced drug hypersensitivity. First, we show that quinine, which normally accumulates inside the DV and therewithin exerts its antimalarial effect, binds extremely tightly to the substrate-binding site of certain isoforms of PfCRTCQR. By doing so it likely blocks the normal physiological function of the protein, which is essential for the parasite’s survival, and the drug thereby gains an additional killing effect. In the second scenario, we show that although amantadine also sequesters within the DV, the parasite’s hypersensitivity to this drug arises from the PfCRTCQR-mediated transport of amantadine from the DV into the cytosol, where it can better access its antimalarial target. In both cases, the mutations that suppress hypersensitivity also abrogate the ability of PfCRTCQR to transport CQ, thus explaining why rescue from hypersensitivity restores the parasite’s sensitivity to this antimalarial. These insights provide a foundation for understanding clinically-relevant observations of inverse drug susceptibilities in the malaria parasite

Transcriptomics modeling of the late-gestation fetal pituitary response to transient hypoxia

Background The late-gestation fetal sheep responds to hypoxia with physiological, neuroendocrine, and cellular responses that aid in fetal survival. The response of the fetus to hypoxia represents a coordinated effort to maximize oxygen transfer from the mother and minimize wasteful oxygen consumption by the fetus. While there have been many studies aimed at investigating the coordinated physiological and endocrine responses to hypoxia, and while immunohistochemical or in situ hybridization studies have revealed pathways supporting the endocrine function of the pituitary, there is little known about the coordinated cellular response of the pituitary to the hypoxia. Results Thirty min hypoxia (from 17.0±1.7 to 8.0±0.8 mm Hg, followed by 30 min normoxia) upregulated 595 and downregulated 790 genes in fetal pituitary (123-132 days' gestation; term = 147 days). Network inference of up- and down- regulated genes revealed a high degree of functional relatedness amongst the gene sets. Gene ontology analysis revealed upregulation of cellular metabolic processes (e.g., RNA synthesis, response to estrogens) and downregulation Conclusions The multiple analytical approaches used in this study suggests that the acute response to 30 min of transient hypoxia in the late-gestation fetus results in reduced cellular metabolism and a pattern of gene expression that is consistent with cellular oxygen and ATP starvation. In this early time point, we see a vigorous gene response. But, like the hypothalamus, the transcriptomic response is not consistent with mediation by HIF-1. If HIF-1 is a significant controller of gene expression in the fetal pituitary after hypoxia, it must be at a later time.Fil: Wood, Charles E.. University of Florida; Estados UnidosFil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Keller Wood, Maureen. University of Florida; Estados Unido

Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex

Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreased fetal PaO2 from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO2 17 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis (n = 3-5 per group). Hypoxia stimulated a transcriptomic response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic systems biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.Fil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Zárate, Miguel A.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Arndt, Thomas J.. University of Florida; Estados UnidosFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados Unido

Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep

The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. Previously, we have shown that the fetal brain is capable of mounting changes in gene expression that are consistent with tissue inflammation. The present study was designed to use transcriptomics and systems biology modeling to test the hypothesis that ketamine reduces or prevents the upregulation of inflammation-related pathways in hypothalamus and hippocampus after transient hypoxic hypoxia. Chronically catheterized fetal sheep (122 ± 5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2∼50%) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. RNA was isolated from fetal hypothalamus and hippocampus collected 24 h after hypoxia, and was analyzed for gene expression using the Agilent 15.5 k ovine microarray. Ketamine, injected 10 min prior to hypoxia, reduced the cerebral immune response activation to the hypoxia in both brain regions. Genes both upregulated by hypoxia and downregulated by ketamine after hypoxia were significantly associated with gene ontology terms and KEGG pathways that are, themselves, associated with the tissue response to exposure to bacteria. We conclude that the results are consistent with interruption of the cellular response to bacteria by ketamine.Fil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Zarate, Miguel A.. University of Florida; Estados UnidosFil: Arndt, Thomas J.. University of Florida; Estados UnidosFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados Unido

The Biological Response to Nanometre-sized Polymer Particles

Recently, nanometre-sized UHMWPE particles generated from hip and knee replacements have been identified in vitro and in vivo. UHMWPE particles in the 0.1-1.0 µm size range have been shown to be more biologically active than larger particles, provoking an inflammatory response implicated in late aseptic loosening of total joint replacements. The biological activity of nanometre-sized particles has not previously been studied. The biological response to clinically-relevant UHMWPE wear particles including nanometre-sized and micrometre-sized, along with polystyrene particles (FluoSpheres 20 nm, 60 nm, 200 nm and 1.0 µm), and nanometre-sized model polyethylene particles (Ceridust 3615®), was determined in terms of osteolytic cytokine release from primary human peripheral blood mononuclear cells (PBMNC’s). Nanometre-sized UHMWPE wear particles, nanometre-sized Ceridust 3615® and 20 nm FluoSpheres had no significant effect on TNF-α, IL-1β, IL-6 and IL-8 release from PBMNC’s at a concentration of 100 μm3 particles per cell after 12 and 24 hours. The micrometre-size UHMWPE wear particles (0.1-1.0 μm) and 60 nm, 200 nm and 1.0 µm FluoSpheres caused significantly elevated osteolytic cytokine release from PBMNC’s. These results indicated that particles below circa 50 nm fail to activate PBMNC’s and that particle size, composition and morphology played a crucial role in cytokine release by particle stimulated macrophages

Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix.

Aurora-A regulates the recruitment of TACC3 to the mitotic spindle through a phospho-dependent interaction with clathrin heavy chain (CHC). Here, we describe the structural basis of these interactions, mediated by three motifs in a disordered region of TACC3. A hydrophobic docking motif binds to a previously uncharacterized pocket on Aurora-A that is blocked in most kinases. Abrogation of the docking motif causes a delay in late mitosis, consistent with the cellular distribution of Aurora-A complexes. Phosphorylation of Ser558 engages a conformational switch in a second motif from a disordered state, needed to bind the kinase active site, into a helical conformation. The helix extends into a third, adjacent motif that is recognized by a helical-repeat region of CHC, not a recognized phospho-reader domain. This potentially widespread mechanism of phospho-recognition provides greater flexibility to tune the molecular details of the interaction than canonical recognition motifs that are dominated by phosphate binding

The Genome and Methylome of a Beetle with Complex Social Behavior,Nicrophorus vespilloides(Coleoptera: Silphidae)

Testing for conserved and novelmechanisms underlying phenotypic evolution requires a diversity of genomes available for comparisonspanning multiple independent lineages. For example, complex social behavior in insects has been investigated primarily witheusocial lineages, nearly all of which are Hymenoptera. If conserved genomic influences on sociality do exist, we need data from awider range of taxa that also vary in their levels of sociality. Here,we present the assembled and annotated genome of the subsocialbeetle Nicrophorus vespilloides, a species long used to investigate evolutionary questions of complex social behavior. We used thisgenome to address two questions. First, do aspects of life history, such as using a carcass to breed, predict overlap in gene modelsmore strongly than phylogeny? We found that the overlap in gene models was similar between N. vespilloides and all other insectgroups regardless of life history. Second, like other insects with highly developed social behavior but unlike other beetles, doesN. vespilloides have DNA methylation?We found strong evidence for an active DNA methylation system. The distribution of methylationwassimilar to other insects with exons having themostmethylatedCpGs. Methylation status appears highly conserved; 85%of themethylated genes in N. vespilloides are alsomethylated in the hymentopteran Nasonia vitripennis. The addition of this genomeadds a coleopteran resource to answer questions about the evolution and mechanistic basis of sociality and to address questionsabout the potential role of methylation in social behavior

Doctors' personal health care choices: A cross-sectional survey in a mixed public/private setting

<p>Abstract</p> <p>Background</p> <p>Among Western countries, it has been found that physicians tend to manage their own illnesses and tend not have their own independent family physicians. This is recognized as a significant issue for both physicians and, by extension, the patients under their care, resulting in initiatives seeking to address this. Physicians' personal health care practices in Asia have yet to be documented.</p> <p>Methods</p> <p>An anonymous cross-sectional postal questionnaire survey was conducted in Hong Kong, China. All 9570 medical practitioners in Hong Kong registered with the Hong Kong Medical Council in 2003 were surveyed. Chi-square tests and logistic regression models were applied.</p> <p>Results</p> <p>There were 4198 respondents to the survey; a response rate of 44%. Two-thirds of respondents took care of themselves when they were last ill, with 62% of these self-medicating with prescription medication. Physicians who were graduates of Hong Kong medical schools, those working in general practice and non-members of the Hong Kong College of Family Physicians were more likely to do so. Physician specialty was found to be the most influential reason in the choice of caregiver by those who had ever consulted another medical practitioner. Only 14% chose consultation with a FM/GP with younger physians and non-Hong Kong medical graduates having a higher likelihood of doing so. Seventy percent of all respondents believed that having their own personal physician was unnecessary.</p> <p>Conclusion</p> <p>Similar to the practice of colleagues in other countries, a large proportion of Hong Kong physicians self-manage their illnesses, take self-obtained prescription drugs and believe they do not need a personal physician. Future strategies to benefit the medical care of Hong Kong physicians will have to take these practices and beliefs into consideration.</p