Co‐production in community mental health services: blurred boundaries or a game of pretend?

The concept of co‐production suggests a collaborative production of public welfare services, across boundaries of participant categories, for example professionals, service users, peer‐workers and volunteers. While co‐production has been embraced in most European countries, the way in which it is translated into everyday practice remains understudied. Drawing on ethnographic data from Danish community mental health services, we attempt to fill this gap by critically investigating how participants interact in an organisational set‐up with blurred boundaries between participant categories. In particular, we clarify under what circumstances the blurred boundaries emerge as believable. Theoretically, we combine Lamont and Molnár's (2002) distinction between symbolic boundaries and social boundaries with Goffman's (1974) microanalysis of “principles of convincingness”. The article presents three findings: (1) co‐production is employed as a symbolic resource for blurring social boundaries; (2) the believability of blurred boundaries is worked up through participants’ access to resources of validation, knowledge and authority; and (3) incongruence between symbolic and social boundaries institutionalises practices where participants merely act ‘as if’ boundaries are blurred. Clarification of the principles of convincingness contributes to a general discussion of how co‐production frames the everyday negotiation of symbolic and social boundaries in public welfare services.     

Semi-Quantitative Calculations of Primary Tumor Metabolic Activity Using F-18 FDG PET/CT as a Predictor of Survival in 92 Patients With High-Grade Bone or Soft Tissue Sarcoma

To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT.A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performed. Clinical data were registered. Accuracy of maximum standardized uptake value of primary tumor (SUV_max) and tumor-to-background (T/B) uptake ratio as prognostic variables and identification of cut-off values to group patients were determined. Kaplan–Meier survival estimates and log-rank test were used to compare survival distributions. Prognostic variables were assessed using Cox proportional hazards regression analysis.Forty-one of 92 patients died during follow-up (45%). Average survival was 6.5 years (95% CI 5.8–7.3 years) and probability of 5-year survival was 52%. Accuracy of SUV_max and T/B uptake ratio as prognostic variables in all patients and during subgroup analysis of patients with STS was significant. No significant results for AUCs were registered in patients with BS. Surgery was independently prognostic for survival throughout multivariate regression analysis of all patients (P = 0.001, HR 3.84) and subgroup analysis (BS: P = 0.02, HR 11.62; STS: P = 0.005, HR 4.13). SUV_max was significant as prognostic variable in all patients (P = 0.02, HR 3.66) and in patients with STS (P = 0.007, HR 3.75). No significant results were demonstrated for T/B uptake ratio.Estimation of primary tumor metabolic activity with pretherapeutic SUV_max using F-18 FDG PET/CT demonstrates independent properties beyond histologic grading for prediction of survival in patients with high-grade STS, but not with high-grade BS.     

The association between idiopathic environmental intolerance and psychological distress,and the influence of social support and recent major life events

Objectives  

Idiopathic environmental intolerance (IEI) is a disorder characterized by non-specific symptoms attributed to common airborne chemicals. Increasing evidence points to an association between IEI and symptoms of psychological distress. However, whether other risk factors influence this association has not been clarified. The objective of this study was to examine the association between psychological distress and IEI and to determine whether the association is confounded by social support and major life events.     

Effects of dietary n-3 and n-6 fatty acids on clinical outcome in a porcine model on post-operative infection

The present study was performed to evaluate the effects of dietary n-3 and n-6 long-chain PUFA (LC-PUFA) on clinical outcome in a porcine model on early aortic vascular prosthetic graft infection (AVPGI). A total of eighty-four pigs were randomised to a 35?d dietary treatment with 10?% (w/w) fish oil (rich in n-3 LC-PUFA), sunflower oil (rich in n-6 LC-PUFA) or animal fat. After 3 weeks of dietary treatment, the pigs had an aortic vascular prosthetic graft inserted, and it was inoculated with Staphylococcus aureus (106 colony-forming units). Changes in selected plasma and erythrocyte n-3 and n-6 LC-PUFA concentrations and in plasma PGE2 metabolite concentration were determined in the 3-week preoperative period. Clinical signs of infection, i.e. rectal temperature, hindquarter function, general appearance and feed intake, were monitored daily in the 14?d post-operative period, and, finally, daily body-weight gain was determined in both periods. The preoperative changes in plasma and erythrocyte n-3 and n-6 LC-PUFA concentrations reflected the fatty acid compositions of the dietary treatments given, and plasma PGE2 metabolite concentration decreased in the fish oil treatment (P?相似文献   

Stoichiometry for activation of neuronal α7 nicotinic receptors

Neuronal α7 nicotinic receptors elicit rapid cation influx in response to acetylcholine (ACh) or its hydrolysis product choline. They contribute to cognition, synaptic plasticity, and neuroprotection and have been implicated in neurodegenerative and neuropsychiatric disorders. α7, however, often localizes distal to sites of nerve-released ACh and binds ACh with low affinity, and thus elicits its biological response with low agonist occupancy. To assess the function of α7 when ACh occupies fewer than five of its identical binding sites, we measured the open-channel lifetime of individual receptors in which four of the five ACh binding sites were disabled. To improve the time resolution of the inherently brief α7 channel openings, background mutations or a potentiator was used to increase open duration. We find that, in receptors with only one intact binding site, the open-channel lifetime is indistinguishable from receptors with five intact binding sites, counter to expectations from prototypical neurotransmitter-gated ion channels where the open-channel lifetime increases with the number of binding sites occupied by agonist. Replacing the membrane-embedded domain of α7 by that of the related 5-HT₃A receptor increases the number of sites that need to be occupied to achieve the maximal open-channel lifetime, thus revealing a unique interdependence between the detector and actuator domains of these receptors. The distinctive ability of a single occupancy to elicit a full biological response adapts α7 to volume transmission, a prevalent mechanism of ACh-mediated signaling in the nervous system and nonneuronal cells.The α7 acetylcholine nicotinic receptors (AChR) are among the most abundant AChRs in the central nervous system, where they are enriched in the medulla, pons, midbrain, thalamus, hippocampus, and cerebral cortex (1). They contribute to cognitive functioning, sensory information processing, attention, working memory, and reward pathways. Decline, disruption, or alterations of cholinergic signaling involving α7 have been implicated in various neurological diseases, such as schizophrenia, epilepsy, autism, Alzheimer’s disease, and addiction (2–6). As a result, α7 has emerged as a novel therapeutic drug target (7, 8).α7 are homomeric receptors from the Cys-loop family of pentameric ligand-gated ion channels. They are composed of three distinct modules: an extracellular domain that carries the agonist binding sites, a transmembrane domain that forms the ion-conducting pore, and an intracellular domain that contributes to ion conductance. They contain five identical binding sites, located at subunit interfaces in the extracellular domain (1, 9).ACh binding leads to a series of conformational changes that open its cation-permeable transmembrane channel, followed by desensitization (10, 11). Hallmarks of α7 receptors include their high Ca²⁺ permeability, full activation by choline (a product of ACh hydrolysis), and extremely fast desensitization (12, 13). The allosteric mechanism by which binding of ACh mediates activation and desensitization remains a central question in the field.Within the central nervous system, α7 receptors localize both pre- and postsynaptically, but they dominantly operate in an extrasynaptic mode (14). Choline is also an efficacious agonist of α7, which further extends the spatial range of cholinergic transmission. This combination of volume transmission and extension of bioactivity by choline is also relevant in nonneuronal cells, such as lymphocytes and macrophages, where α7 is involved in anti-inflammatory responses (15, 16), and in sperm cells where α7 has a role in fertilization (17).α7 AChRs are thus physiological targets for both ACh and choline, but concentrations of these agonists are expected to be low and to change in proportion to overall neuronal activity, unlike at classical, on or off, fast cholinergic synapses. Furthermore, both ACh and choline bind to α7 with low affinity so that, under physiological conditions, agonist occupancy of the binding sites will be low. However, neurotransmitter-gated ion channels contain multiple agonist binding sites, and classical observations show that occupancy of multiple sites maximizes open-channel stability (11). Thus, we sought to compare open-channel stability of α7 with agonist bound to one or all five binding sites.To this end, we generated α7 AChRs from two types of subunits, one that formed a disabled binding site and another that formed a normal binding site. To determine the number of intact binding sites in individual pentamers, we tagged one of the subunits with mutations that alter unitary conductance and then used patch-clamp recording to monitor the open channel lifetime of receptors with defined numbers of intact binding sites.     

Intestinal tissue transglutaminase in coeliac disease of children and adults: ultrastructural localization and variation in expression

Background: Tissue transglutaminase is the main antigen for the anti-endomysial antibodies used for diagnosis of coeliac disease and can with some specificity in vitro deamidate gliadins generating potent epitopes. The intestinal levels and the ultrastructural localization of tissue transglutaminase in normal and affected persons were investigated to provide further information on its role in this disease. Intestinal biopsies were taken from normal and coeliac children and adults. Methods: The level of transglutaminase was analysed by means of a quantitative enzymatic assay and its ultrastructural localization by immunogold electronmicroscopy using a monoclonal antibody against tissue transglutaminase. Results: In relation to normal individuals, the enzymatic activity of tissue transglutaminase in adult coeliac patients was increased. The enzyme was found in the enterocytes and in increased amount just beneath the enterocytes, where cytosolic and nuclear labelling of distinct elongated cells was seen in addition to extracellular labelling close to collagen fibrils. In children, the enzymatic activity and the immunogold labelling could not be shown to be related to disease. In all cases the enzyme activity was EDTA-sensitive. Conclusions: The increased amount of tissue transglutaminase activity in coeliac adults was shown to be due to the appearance of the enzyme in enterocytes and increased expression in the lamina propria. No evidence was found to support the idea of a changed localization or changed amounts as primary elements in coeliac disease pathogenesis, nor for the involvement of non-calcium dependent microbial transglutaminases.     

The measurement of fractionated bilirubin by Ektachem film slides. Method validation and comparison of conjugated bilirubin measurements with direct bilirubin in obstructive and hepatocellular jaundice

The authors evaluated the Kodak Ektachem Slides for total, "direct," conjugated, unconjugated, and albumin-bound ("delta") bilirubin. For various concentrations of control material, the precision (CV) within- and between-day ranged from 1.7 to 2.4% (2.8-6.6%) for total bilirubin, 0.8-4.2% (1.6-11.5%) for unconjugated bilirubin, and 1.6-9.5% (2.6-20.7%) for conjugated bilirubin. The Ektachem total and "direct" bilirubin assays demonstrated excellent correlation with the Jendrassik and Grof procedure; a 30% difference was observed, however, between absolute numbers with the two direct bilirubin methods. We found the measurement of true conjugated bilirubin by the Kodak Method to be superior to the measurement of "direct" bilirubin in following the response to treatment of various hepatic disorders manifested by extrahepatic and intrahepatic biliary obstruction.     

End-plate acetylcholine receptor: structure, mechanism, pharmacology, and disease

The synapse is a localized neurohumoral contact between a neuron and an effector cell and may be considered the quantum of fast intercellular communication. Analogously, the postsynaptic neurotransmitter receptor may be considered the quantum of fast chemical to electrical transduction. Our understanding of postsynaptic receptors began to develop about a hundred years ago with the demonstration that electrical stimulation of the vagus nerve released acetylcholine and slowed the heart beat. During the past 50 years, advances in understanding postsynaptic receptors increased at a rapid pace, owing largely to studies of the acetylcholine receptor (AChR) at the motor endplate. The endplate AChR belongs to a large superfamily of neurotransmitter receptors, called Cys-loop receptors, and has served as an exemplar receptor for probing fundamental structures and mechanisms that underlie fast synaptic transmission in the central and peripheral nervous systems. Recent studies provide an increasingly detailed picture of the structure of the AChR and the symphony of molecular motions that underpin its remarkably fast and efficient chemoelectrical transduction.