Ignicoccus hospitalis and Nanoarchaeum equitans: ultrastructure, cell–cell interaction, and 3D reconstruction from serial sections of freeze-substituted cells and by electron cryotomography

Ultrastructure and intercellular interaction of Ignicoccus hospitalis and Nanoarchaeum equitans were investigated using two different electron microscopy approaches, by three-dimensional reconstructions from serial sections, and by electron cryotomography. Serial sections were assembled into 3D reconstructions, for visualizing the unusual complexity of I. hospitalis, its huge periplasmic space, the vesiculating cytoplasmic membrane, and the outer membrane. The cytoplasm contains fibres which are reminiscent to a cytoskeleton. Cell division in I. hospitalis is complex, and different to that in Euryarchaeota or Bacteria. An irregular invagination of the cytoplasmic membrane is followed by separation of the two cytoplasms. Simultaneous constriction of cytoplasmic plus outer membrane is not observed. Cells of N. equitans show a classical mode of cell division, by constriction in the mid-plane. Their cytoplasm exhibits two types of fibres, elongated and ring-shaped. Electron micrographs of contact sites between I. hospitalis and N. equitans exhibit two modes of interaction. One is indirect and mediated by thin fibres; in other cells the two cell surfaces are in direct contact. The two membranes of I. hospitalis cells are frequently seen in direct contact, possibly a prerequisite for transporting metabolites or substrates from the cytoplasm of one cell to the other. Rarely, a transport based on cargo vesicles is observed between I. hospitalis and N. equitans

Making sense of health information technology implementation: A qualitative study protocol

BACKGROUND: Implementing new practices, such as health information technology (HIT), is often difficult due to the disruption of the highly coordinated, interdependent processes (e.g., information exchange, communication, relationships) of providing care in hospitals. Thus, HIT implementation may occur slowly as staff members observe and make sense of unexpected disruptions in care. As a critical organizational function, sensemaking, defined as the social process of searching for answers and meaning which drive action, leads to unified understanding, learning, and effective problem solving -- strategies that studies have linked to successful change. Project teamwork is a change strategy increasingly used by hospitals that facilitates sensemaking by providing a formal mechanism for team members to share ideas, construct the meaning of events, and take next actions. METHODS: In this longitudinal case study, we aim to examine project teams' sensemaking and action as the team prepares to implement new information technology in a tiertiary care hospital. Based on management and healthcare literature on HIT implementation and project teamwork, we chose sensemaking as an alternative to traditional models for understanding organizational change and teamwork. Our methods choices are derived from this conceptual framework. Data on project team interactions will be prospectively collected through direct observation and organizational document review. Through qualitative methods, we will identify sensemaking patterns and explore variation in sensemaking across teams. Participant demographics will be used to explore variation in sensemaking patterns. DISCUSSION: Outcomes of this research will be new knowledge about sensemaking patterns of project teams, such as: the antecedents and consequences of the ongoing, evolutionary, social process of implementing HIT; the internal and external factors that influence the project team, including team composition, team member interaction, and interaction between the project team and the larger organization; the ways in which internal and external factors influence project team processes; and the ways in which project team processes facilitate team task accomplishment. These findings will lead to new methods of implementing HIT in hospitals

Mutual adaptation of a membrane protein and its lipid bilayer during conformational changes

The structural elucidation of membrane proteins continues to gather pace, but we know little about their molecular interactions with the lipid environment or how they interact with the surrounding bilayer. Here, with the aid of low-resolution X-ray crystallography, we present direct structural information on membrane interfaces as delineated by lipid phosphate groups surrounding the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) in its phosphorylated and dephosphorylated Ca(2+)-free forms. The protein-lipid interactions are further analysed using molecular dynamics simulations. We find that SERCA adapts to membranes of different hydrophobic thicknesses by inducing local deformations in the lipid bilayers and by undergoing small rearrangements of the amino-acid side chains and helix tilts. These mutually adaptive interactions allow smooth transitions through large conformational changes associated with the transport cycle of SERCA, a strategy that may be of general nature for many membrane proteins

Kinetic and mesoscopic non-equilibrium description of the Ca2+ pump: A comparison

We analyse the operation of the Ca2?-ATPase ion pump using a kinetic cycle diagram. Using the methodology of Hill, we obtain the cycle fluxes, entropy production and efficiency of the pump. We compare these results with a mesoscopic non-equilibrium description of the pump and show that the kinetic and mesoscopic pictures are in accordance with each other. This gives further support to the mesoscopic theory, which is less restricted and also can include the heat flux as a variable. We also show how motors can be characterised in terms of unidirectional backward fluxes. We proceed to show how the mesoscopic approach can be used to identify fast and slow steps of the model in terms of activation energies, and how this can be used to simplify the kinetic diagram.Process and Energy LaboratoryMechanical, Maritime and Materials Engineerin

Efficacy and Safety of a Novel Mucoadhesive Clobetasol Patch for Treatment of Erosive Oral Lichen Planus

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for oral lichen planus (OLP). We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin® -CLO) for the treatment of OLP. METHODS: Patients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double-blind, placebo-controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin® -CLO) in OLP across Europe, Canada and USA. Patients were randomized to placebo (non-medicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life. RESULTS: Data were analyzed and expressed as mean [SD]. One hundred thirty-eight (138) patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20-μg Rivelin® -CLO patches demonstrated significant improvement with ulcer area (P=0.047), symptom severity (P=0.001), disease activity (P=0.022), pain (P=0.012), and quality of life (P=0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20-µg group (25/32) patients compared to the placebo group (11/30), (P=0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%). CONCLUSIONS: Rivelin® -CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile