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Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS.
Lipoproteins isolated from normal human plasma can bind and neutralize bacterial lipopolysaccharide (LPS) and may represent an important mechanism in host defense against gram-negative septic shock. Recent studies have shown that experimentally elevating the levels of circulating high-density lipoproteins (HDL) provides protection against death in animal models of endotoxic shock. We sought to define the components of HDL that are required for neutralization of LPS. To accomplish this we have studied the functional neutralization of LPS by native and reconstituted HDL using a rapid assay that measures the CD14-dependent activation of leukocyte integrins on human neutrophils. We report here that reconstituted HDL particles (R-HDL), prepared from purified apolipoprotein A-I (apoA-I) combined with phospholipid and free cholesterol, are not sufficient to neutralize the biologic activity of LPS. However, addition of recombinant LPS binding protein (LBP), a protein known to transfer LPS to CD14 and enhance responses of cells to LPS, enabled prompt binding and neutralization of LPS by R-HDL. Thus, LBP appears capable of transferring LPS not only to CD14 but also to lipoprotein particles. In contrast with R-HDL, apoA-I containing lipoproteins (LpA-I) isolated from plasma by selected affinity immunosorption (SAIS) on an anti-apoA-I column, neutralized LPS without addition of exogenous LBP. Several lines of evidence demonstrated that LBP is a constituent of LpA-I in plasma. Passage of plasma over an anti-apoA-I column removed more than 99% of the LBP detectable by ELISA, whereas 31% of the LBP was recovered by elution of the column. Similarly, the ability of plasma to enable activation of neutrophils by LPS (LBP/Septin activity) was depleted and recovered by the same process. Furthermore, an immobilized anti-LBP monoclonal antibody coprecipitated apoA-I. The results described here suggest that in addition to its ability to transfer LPS to CD14, LBP may also transfer LPS to lipoproteins. Since LBP appears to be physically associated with lipoproteins in plasma, it is positioned to play an important role in the neutralization of LPS
Being Occupied With What Matters in Advanced Age
This article illuminates one key finding of an interpretive phenomenological study that brought an occupational lens to exploring how elders experience ageing in their everyday lives. Fifteen community-dwelling, New Zealand elders aged 71 to 97, 4 Maori and 11 non-Maori, were purposively recruited. Data were gathered through individual interviews focused on stories of everyday moments and photographs of the participantâs hands only while engaged in doing a chosen occupation. Discrete stories were drawn from the narrative data and interpreted, guided by Gadamerian hermeneutics and Heideggerian phenomenology. The notion of âdoing what mattersâ emerged as participants spoke of having one occupation that was of primary importance to them. This one compelling pursuit showed as an enduring interest over time, illuminating the temporal unity of past, present and future in advanced age. Accordingly, the boundaries of researching occupational engagement in advanced age ought to be redefined. Instead of a current emphasis on understanding eldersâ participation in daily activities, activity categories and patterns, occupational science research might deepen the focus to understand how engagement in subjectively compelling occupations is associated with ageing well and longevity
The glia response after peripheral nerve injury: A comparison between Schwann cells and olfactory ensheathing cells and their uses for neural regenerative therapies
The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory nerve, and Schwann cells (SCs), which are present in the rest of the PNS. These two glial types share many similar morphological and functional characteristics but also exhibit key differences. The olfactory nerve is constantly turning over throughout life, which means OECs are continuously stimulating neural regeneration, whilst SCs only promote regeneration after direct injury to the PNS. This review presents a comparison between these two PNS systems in respect to normal physiology, developmental anatomy, glial functions and their responses to injury. A thorough understanding of the mechanisms and differences between the two systems is crucial for the development of future therapies using transplantation of peripheral glia to treat neural injuries and/or disease.Griffith Health, School of Nursing and MidwiferyFull Tex
Aging Just Is: Illuminating Its That-being, How-being & What-being
Aging is part of life. Its natural occurrence means that, by virtue of living, each and every one of us exists toward being aged. It just happens. In the usual course of life it cannot, not happen. Aging is always already there within our human finiteness. Thus, as something which is unremitting, the being toward aging is present from the event of coming into the world to the moment of going out of it.
I offer here a glimpse at a hermeneutic interpretation of the phenomenon of aging. Philosophically, Heideggerâs understandings of the âthat-being,â the âhow-beingâ and the âwhat-beingâ of phenomena are used to illuminate the notion that âaging just is.â The deep soil in which the interpretation is grounded is the everyday stories told by 15 New Zealand elders. An outline of the studyâs design and methods is given in the abstract for this presentation. The photographs shown are not those of the studyâs participants
Being occupied in the everyday
This chapter draws on the stories told by elder New Zealanders as a way of illuminating the deeply contextual, habitual, relational and precarious nature of engaging in everyday occupations. In the telling we hear how routines matter because they give shape and structure to a day. Having a purpose, however, calls one into engaged activity with enthusiasm. Everyday occupations offer connectedness in time and with others. They can give a sense of continuity which stretches back into the distant past and which projects forward into the future. Memories and deeply held social customs matter. As such, those important to oneâs life who have died still stay as part of the livingsâ relational context. Paradoxically, we also hear how the ordinariness of familiar occupations is the context for the unfamiliar to be made visible. Precariousness is ever-present. These and other complexities of being in the everyday in advanced age, such as aloneness, and intergenerational relationships are analyzed vis-Ă -vis occupation using both a phenomenological and a transactional perspective. It is only by understanding the holistic, contextual nature of engaging in everyday occupations that one comes to recognize that when working with older people one must sensitively listen and think before acting. A transactional perspective provides the conceptual tools to support this practice
A Guide to RBF-Generated Finite Differences for Nonlinear Transport: Shallow Water Simulations on a Sphere
The current paper establishes the computational efficiency and accuracy of the RBF-FD method for large-scale geoscience modeling with comparisons to state-of-the-art methods as high-order discontinuous Galerkin and spherical harmonics, the latter using expansions with close to 300,000 bases. The test cases are demanding fluid flow problems on the sphere that exhibit numerical challenges, such as Gibbs phenomena, sharp gradients, and complex vortical dynamics with rapid energy transfer from large to small scales over short time periods. The computations were possible as well as very competitive due to the implementation of hyperviscosity on large RBF stencil sizes (corresponding roughly to 6th to 9th order methods) with up to O(105) nodes on the sphere. The RBF-FD method scaled as O(N) per time step, where N is the total number of nodes on the sphere. In Appendix A, guidelines are given on how to chose parameters when using RBF-FD to solve hyperbolic PDEs
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Healthcare Provider Attitudes Towards the Problem List in an Electronic Health Record: A Mixed-Methods Qualitative Study
Background: The problem list is a key part of the electronic health record (EHR) that allows practitioners to see a patientâs diagnoses and health issues. Yet, as the content of the problem list largely represents the subjective decisions of those who edit it, patientsâ problem lists are often unreliable when shared across practitioners. The lack of standards for how the problem list is compiled in the EHR limits its effectiveness in improving patient care, particularly as a resource for clinical decision support and population management tools. The purpose of this study is to discover practitioner opinions towards the problem list and the logic behind their decisions during clinical situations. Materials and methods: An observational cross-sectional study was conducted at two major Boston teaching hospitals. Practitionersâ opinions about the problem list were collected through both in-person interviews and an online questionnaire. Questions were framed using vignettes of clinical scenarios asking practitioners about their preferred actions towards the problem list. Results: These data confirmed prior research that practitioners differ in their opinions over managing the problem list, but in most responses to a questionnaire, there was a common approach among the relative majority of respondents. Further, basic demographic characteristics of providers (age, medical experience, etc.) did not appear to strongly affect attitudes towards the problem list. Conclusion: The results supported the premise that policies and EHR tools are needed to bring about a common approach. Further, the findings helped identify what issues might benefit the most from a defined policy and the level of restriction a problem list policy should place on the addition of different types of information
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