An exploratory open-label multicentre phase I/II trial evaluating the safety and efficacy of postnatal or prenatal and postnatal administration of allogeneic expanded fetal mesenchymal stem cells for the treatment of severe osteogenesis imperfecta in infants and fetuses: the BOOSTB4 trial protocol.

INTRODUCTION: Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4. METHODS AND ANALYSIS: BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1-5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in COL1A1 or COL1A2 can be included in the trial.Each subject receives four intravenous doses of 3×106/kg BOOST cells at 4 month intervals, with 48 (doses 1-2) or 24 (doses 3-4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally.The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover. ETHICS AND DISSEMINATION: The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482.

Biologic therapy in rare eosinophil-associated disorders: remaining questions and translational research opportunities.

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.

Responsibility for Funding Refractive Correction in Publicly Funded Health Care Systems: An Ethical Analysis.

Allocating on the basis of need is a distinguishing principle in publicly funded health care systems. Resources ought to be directed to patients, or the health program, where the need is considered greatest. In Sweden support of this principle can be found in health care legislation. Today however some domains of what appear to be health care needs are excluded from the responsibilities of the publicly funded health care system. Corrections of eye disorders known as refractive errors is one such domain. In this article the moral legitimacy of this exception is explored. Individuals with refractive errors need spectacles, contact lenses or refractive surgery to do all kinds of thing, including participating in everyday activities, managing certain jobs, and accomplishing various goals in life. The relief of correctable visual impairments fits well into the category of what we typically consider a health care need. The study of refractive errors does belong to the field of medical science, interventions to correct such errors can be performed by medical means, and the skills of registered health care professionals are required when it comes to correcting refractive error. As visual impairments caused by other conditions than refractive errors are treated and funded within the public health care system in Sweden this is an inconsistency that needs to be addressed.

Lipase-Catalyzed Synthesis of Renewable Plant Oil-Based Polyamides.

Enzyme catalyzed synthesis of renewable polyamides was investigated using Candida antarctica lipase B. A fatty acid-derived AB-type functional monomer, having one amine and one methyl ester functionality, was homopolymerized at 80 and 140 °C. Additionally, the organobase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) was used as a catalyst. The results from the two catalysts were comparable. However, the amount of lipase added was 1.2 × 103 times lower, showing that the lipase was a more efficient catalyst for this system as compared to TBD. Moreover, the AB-type monomer was copolymerized with 1,12-diaminododecane to synthesize oligoamides of two different lengths.

Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma.

Rationale: Extracellular DNA (eDNA) and neutrophil extracellular traps (NETs) are implicated in multiple inflammatory diseases. NETs mediate inflammasome activation and IL-1ß secretion from monocytes and cause airway epithelial cell injury, but the role of eDNA, NETs, and IL-1ß in asthma is uncertain. Objectives: To characterize the role of activated neutrophils in severe asthma through measurement of NETs and inflammasome activation. Methods: We measured sputum eDNA in induced sputum from 399 patients with asthma in the Severe Asthma Research Program-3 and in 94 healthy control subjects. We subdivided subjects with asthma into eDNA-low and -high subgroups to compare outcomes of asthma severity and of neutrophil and inflammasome activation. We also examined if NETs cause airway epithelial cell damage that can be prevented by DNase. Measurements and Main Results: We found that 13% of the Severe Asthma Research Program-3 cohort is "eDNA-high," as defined by sputum eDNA concentrations above the upper 95th percentile value in health. Compared with eDNA-low patients with asthma, eDNA-high patients had lower Asthma Control Test scores, frequent history of chronic mucus hypersecretion, and frequent use of oral corticosteroids for maintenance of asthma control (all P values <0.05). Sputum eDNA in asthma was associated with airway neutrophilic inflammation, increases in soluble NET components, and increases in caspase 1 activity and IL-1ß (all P values <0.001). In in vitro studies, NETs caused cytotoxicity in airway epithelial cells that was prevented by disruption of NETs with DNase. Conclusions: High extracellular DNA concentrations in sputum mark a subset of patients with more severe asthma who have NETs and markers of inflammasome activation in their airways.

Enzymatically Synthesized Vinyl Ether-Disulfide Monomer Enabling an Orthogonal Combination of Free Radical and Cationic Chemistry toward Sustainable Functional Networks.

This work demonstrates a versatile and environmentally friendly route for the development of new orthogonal monomers that can be used for postfunctionalizable polymer networks. A monomer containing both vinyl ether (VE) and cyclic disulfide moieties was synthesized via enzyme catalysis under benign reaction conditions. The bifunctional monomer could be polymerized to form macromolecues with differing architectures by the use of either cationic or radical photo polymerization. When cationic polymerization was performed, a linear polymer was obtained with pendant disulfide units in the side chain, whereas in the presence of radical initiator, the VE reacted with the disulfide to yield a branched structure. The monomer was thereafter used to design networks that could be postfunctionalized; the monomer was cross-linked with cationic initiation together with a difunctional VE oligomer and after cross-linking the unreacted disulfides were coupled to Rhodamine-VE by radical UV-initiation.

Control of cytokine-driven eosinophil migratory behavior by TGF-beta-induced protein (TGFBI) and periostin.

Periostin, which is induced by interleukin (IL)-13, is an extracellular matrix (ECM) protein that supports αMß2 integrin-mediated adhesion and migration of IL-5-stimulated eosinophils. Transforming growth factor (TGF)-ß-induced protein (TGFBI) is a widely expressed periostin paralog known to support monocyte adhesion. Our objective was to compare eosinophil adhesion and migration on TGFBI and periostin in the presence of IL-5-family cytokines. Eosinophil adhesion after 1 h and random motility over 20 h in the presence of various concentrations of IL-5, IL-3, or granulocyte macrophage-colony stimulating factor (GM-CSF) were quantified in wells coated with various concentrations of TGFBI or periostin. Results were compared to video microscopy of eosinophils. Cytokine-stimulated eosinophils adhered equivalently well to TGFBI or periostin in a coating concentration-dependent manner. Adhesion was blocked by anti-αMß2 and stimulated at the lowest concentration by GM-CSF. In the motility assay, periostin was more potent than TGFBI, the coating-concentration effect was bimodal, and IL-3 was the most potent cytokine. Video microscopy revealed that under the optimal coating condition of 5 µg/ml periostin, most eosinophils migrated persistently and were polarized and acorn-shaped with a ruffling forward edge and granules gathered together, in front of the nucleus. On 10 µg/ml periostin or TGFBI, more eosinophils adopted a flattened pancake morphology with dispersed granules and nuclear lobes, and slower migration. Conversion between acorn and pancake morphologies were observed. We conclude that TGFBI or periostin supports two modes of migration by IL-5 family cytokine-activated eosinophils. The rapid mode is favored by intermediate protein coatings and the slower by higher coating concentrations. We speculate that eosinophils move by haptotaxis up a gradient of adhesive ECM protein and then slow down to surveil the tissue.

Does subjective improvement in adults with intracranial arachnoid cysts justify surgical treatment?

OBJECTIVE Subjective improvement of patients who have undergone surgery for intracranial arachnoid cysts has justified surgical treatment. The current study aimed to evaluate the outcome of surgical treatment for arachnoid cysts using standardized interviews and assessments of neuropsychological function and balance. The relationship between arachnoid cyst location, postoperative improvement, and arachnoid cyst volume was also examined. METHODS The authors performed a prospective, population-based study. One hundred nine patients underwent neurological, neuropsychological, and physiotherapeutic examinations. The arachnoid cysts were considered symptomatic in 75 patients, 53 of whom agreed to undergo surgery. In 32 patients, results of the differential diagnosis revealed that the symptoms were due to a different underlying condition and were unrelated to an arachnoid cyst. Neuropsychological testing included target reaction time, Grooved Pegboard, Rey Auditory Verbal Learning, Rey Osterrieth complex figure, and Stroop tests. Balance tests included the extended Falls Efficacy Scale, Romberg, and sharpened Romberg with open and closed eyes. The tests were repeated 5 months postoperatively. Cyst volume was pre- and postoperatively measured using OsiriX software. RESULTS Patients who underwent surgery did not have results on balance and neuropsychological tests that were different from patients who declined or had symptoms unrelated to the arachnoid cyst. Patients with a temporal arachnoid cyst performed within the normal range on the neuropsychological tests. Seventy-seven percent of the patients who underwent surgery reported improvement, yet there were no differences in test results before and after surgery. Arachnoid cysts in the temporal region and posterior fossa did not influence the preoperative results of neuropsychological and motor tests. The arachnoid cyst volume decreased postoperatively (p < 0.0001), but there was no relationship between volume reduction and clinical improvement. CONCLUSIONS The results of this study speak against objectively verifiable improvement following surgical treatment in adults with intracranial arachnoid cysts.

Novel sustainable synthesis of vinyl ether ester building blocks, directly from carboxylic acids and the corresponding hydroxyl vinyl ether, and their photopolymerization.

Increased environmental awareness has led to a demand for sustainable, bio-based materials. Consequently, the development of new benign synthesis pathways utilizing a minimum of reaction steps and available bio-based building blocks is needed. In the present study, vinyl ether alcohols and functional carboxylic acids were used to synthesize bifunctional vinyl ether esters using the immobilized enzyme Candida antarctica lipase B as a catalyst. Vinyl ethers are attractive alternatives to (meth)acrylates due to low allergenic hazards, low toxicity, and fast polymerization; however, difficult synthesis limits the monomer availability. The synthesis was performed in one-pot and the described method was successful within a broad temperature range (22-90 °C) and in various organic solvents as well as in the bulk. The synthesis of different vinyl ether esters reached high conversions (above 90%) after less than 1 h and products were purified by removing the enzyme by filtration using only small amounts of acetone. This approach is a straightforward route to reach monomers with multiple types of functionalities that can be used as different photo-curable thermoset resins. In this work, this was demonstrated by polymerizing the monomers with cationic and radical UV-polymerization. By changing the functional carboxylic acids, the architecture of the final polymer can be tailored, herein demonstrated by two examples. In the developed versatile method, carboxylic acids can be used directly as acyl donors, constituting a more sustainable alternative to the carboxylic acid derivatives used today.

Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma.

RATIONALE: Mepolizumab, an IL-5-blocking antibody, reduces exacerbations in patients with severe eosinophilic asthma. Mepolizumab arrests eosinophil maturation; however, the functional phenotype of eosinophils that persist in the blood and airway after administration of IL-5 neutralizing antibodies has not been reported. OBJECTIVES: To determine the effect of anti-IL-5 antibody on the numbers and phenotypes of allergen-induced circulating and airway eosinophils. METHODS: Airway inflammation was elicited in participants with mild allergic asthma by segmental allergen challenge before and 1 month after a single intravenous 750-mg dose of mepolizumab. Eosinophils were examined in blood, bronchoalveolar lavage, and endobronchial biopsies 48 hours after challenge. MEASUREMENTS AND MAIN RESULTS: Segmental challenge without mepolizumab induced a rise in circulating eosinophils, bronchoalveolar lavage eosinophilia, and eosinophil peroxidase deposition in bronchial mucosa. IL-5 neutralization before allergen challenge abolished the allergen-induced rise in circulating eosinophils and expression of IL-3 receptors, whereas airway eosinophilia and eosinophil peroxidase deposition were blunted but not eliminated. Before mepolizumab treatment, bronchoalveolar lavage eosinophils had more surface IL-3 and granulocyte-monocyte colony-stimulating factor receptors, CD69, CD44, and CD23 and decreased IL-5 and eotaxin receptors than blood eosinophils. This activation phenotype indicated by bronchoalveolar lavage eosinophil surface markers, as well as the release of eosinophil peroxidase by eosinophils in the bronchial mucosa, was maintained after mepolizumab. CONCLUSIONS: Mepolizumab reduced airway eosinophil numbers but had a limited effect on airway eosinophil activation markers, suggesting that these cells retain functionality. This observation may explain why IL-5 neutralization reduces but does not completely eradicate asthma exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT00802438).

Endogenous Semaphorin-7A Impedes Human Lung Fibroblast Differentiation.

Semaphorin-7A is a glycosylphosphatidylinositol-anchored protein, initially characterized as an axon guidance protein. Semaphorin-7A also contributes to immune cell regulation and may be an essential pro-fibrotic factor when expressed by non-fibroblast cell types (exogenous). In mouse models, semaphorin-7A was shown to be important for TGF-ß1-induced pulmonary fibrosis characterized by myofibroblast accumulation and extracellular matrix deposition, but the cell-specific role of semaphorin-7A was not examined in fibroblasts. The purpose of this study is to determine semaphorin-7A expression by fibroblasts and to investigate the function of endogenously expressed semaphorin-7A in primary human lung fibroblasts (HLF). Herein, we show that non-fibrotic HLF expressed high levels of cell surface semaphorin-7A with little dependence on the percentage of serum or recombinant TGF-ß1. Semaphorin-7A siRNA strongly decreased semaphorin-7A mRNA expression and reduced cell surface semaphorin-7A. Reduction of semaphorin-7A induced increased proliferation and migration of non-fibrotic HLF. Also, independent of the presence of TGF-ß1, the decline of semaphorin-7A by siRNA was associated with increased α-smooth muscle actin production and gene expression of periostin, fibronectin, laminin, and serum response factor (SRF), indicating differentiation into a myofibroblast. Conversely, overexpression of semaphorin-7A in the NIH3T3 fibroblast cell line reduced the production of pro-fibrotic markers. The inverse association between semaphorin-7A and pro-fibrotic fibroblast markers was further analyzed using HLF from idiopathic pulmonary fibrosis (IPF) (n = 6) and non-fibrotic (n = 7) lungs. Using these 13 fibroblast lines, we observed that semaphorin-7A and periostin expression were inversely correlated. In conclusion, our study indicates that endogenous semaphorin-7A in HLF plays a role in maintaining fibroblast homeostasis by preventing up-regulation of pro-fibrotic genes. Therefore, endogenous and exogenous semaphorin-7A may have opposite effects on the fibroblast phenotype.

Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts.

BACKGROUND: Severe asthma is a complex heterogeneous disease associated with older age and obesity. The presence of eosinophilic (type 2) inflammation in some but not all patients with severe asthma predicts responsiveness to current treatments, but new treatment approaches will require a better understanding of non-type 2 mechanisms of severe asthma. We considered the possibility that systemic inflammation, which arises in subgroups of obese and older patients, increases the severity of asthma. Interleukin-6 (IL-6) is a biomarker of systemic inflammation and metabolic dysfunction, and we aimed to explore the association between IL-6 concentrations, metabolic dysfunction, and asthma severity. METHODS: In this cross-sectional analysis, patients were recruited from two cohorts: mainly non-severe asthmatics from the University of California San Francisco (UCSF) and mainly severe asthmatics from the Severe Asthma Research Program (SARP). We generated a reference range for plasma IL-6 in a cohort of healthy control patients. We compared the clinical characteristics of asthmatics with plasma IL-6 concentrations above (IL-6 high) and below (IL-6 low) the upper 95% centile value for plasma IL-6 concentration in the healthy cohort. We also compared how pulmonary function, frequency of asthma exacerbations, and frequency of severe asthma differed between IL-6 low and IL-6 high asthma populations in the two asthma cohorts. FINDINGS: Between Jan 1, 2005, and Dec 31, 2014, we recruited 249 patients from UCSF and between Nov 1, 2012, and Oct 1, 2014, we recruited 387 patients from SARP. The upper 95th centile value for plasma IL-6 concentration in the healthy cohort (n=93) was 3·1 pg/mL, and 14% (36/249) of UCSF cohort and 26% (102/387) of the SARP cohort had plasma IL-6 concentrations above this upper limit. The IL-6 high patients in both asthma cohorts had a significantly higher average BMI (p<0·0001) and a higher prevalence of hypertension (p<0·0001) and diabetes (p=0·04) than the IL-6 low patients. IL-6 high patients also had significantly worse lung function and more frequent asthma exacerbations than IL-6 low patients (all p values <0·0001). Although 80% (111/138) of IL-6 high asthmatic patients were obese, 62% (178/289) of obese asthmatic patients were IL-6 low. Among obese patients, the forced expiratory volume in 1 s (FEV1) was significantly lower in IL-6 high than in IL-6 low patients (mean percent predicted FEV1=70·8% [SD 19·5] vs 78·3% [19·7]; p=0·002), and the percentage of patients reporting an asthma exacerbation in the past 1-2 years was higher in IL-6 high than in IL-6 low patients (66% [73/111] vs 48% [85/178]; p=0·003). Among non-obese asthmatics, FEV1 values and the frequency of asthma exacerbations within the past 1-2 years were also significantly worse in IL-6 high than in IL-6 low patients (mean FEV1 66·4% [SD 23·1] vs 83·2% [20·4] predicted; p<0·0001; 59% [16/27] vs 34% [108/320]; p=0·01). INTERPRETATION: Systemic IL-6 inflammation and clinical features of metabolic dysfunction, which occur most commonly in a subset of obese asthma patients but also in a small subset of non-obese patients, are associated with more severe asthma. These data provide strong rationale to undertake clinical trials of IL-6 inhibitors or treatments that reduce metabolic dysfunction in a subset of patients with severe asthma. Plasma IL-6 is a biomarker that could guide patient stratification in these trials. FUNDING: NIH and the Parker B Francis Foundation.

The Peripheral Blood Eosinophil Proteome.

A system-wide understanding of biological processes requires a comprehensive knowledge of the proteins in the biological system. The eosinophil is a type of granulocytic leukocyte specified early in hematopoietic differentiation that participates in barrier defense, innate immunity, and allergic disease. The proteome of the eosinophil is largely unannotated with under 500 proteins identified. We now report a map of the nonstimulated peripheral blood eosinophil proteome assembled using two-dimensional liquid chromatography coupled with high-resolution mass spectrometry. Our analysis yielded 100,892 unique peptides mapping to 7,086 protein groups representing 6,813 genes as well as 4,802 site-specific phosphorylation events. We account for the contribution of platelets that routinely contaminate purified eosinophils and report the variability in the eosinophil proteome among five individuals and proteomic changes accompanying acute activation of eosinophils by interleukin-5. Our deep coverage and quantitative analyses fill an important gap in the existing maps of the human proteome and will enable the strategic use of proteomics to study eosinophils in human diseases.

IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common ß-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions.

Periostin and TGF-ß-induced protein: Two peas in a pod?

Periostin (PN) and TGF-ß-induced protein (ßig-h3) are paralogs that contain a single emilin and four fasciclin-1 modules and are secreted from cells. PN receives attention because of its up-regulation in cancer and degenerative and allergic diseases. ßig-h3 is highly enriched in cornea and best known for harboring mutations in humans associated with corneal dystrophies. Both proteins are expressed widely, and many functions, some over-lapping, have been attributed to PN and ßig-h3 based on biochemical, cell culture, and whole animal experiments. We attempt to organize this knowledge so as to facilitate research on these interesting and incompletely understood proteins. We focus particularly on whether PN and ßig-h3 are modified by vitamin K-dependent γ-glutamyl carboxylation, a question of considerable importance given the profound effects of γ-carboxylation on structure and function of other proteins. We consider the roles of PN and ßig-h3 in formation of extracellular matrix and as ligands for integrin receptors. We attempt to reconcile the contradictory results that have arisen concerning the role of PN, which has emerged as a marker of TH2 immunity, in murine models of allergic asthma. Finally, when possible we compare and contrast the structures and functions of the two proteins.

Health-care professionals' documentation of wellbeing in patients following open heart surgery: a content analysis of medical records.

AIM: To explore health-care professionals' documentation of patient wellbeing in the first five months after open heart surgery. BACKGROUND: Open heart surgery (coronary artery bypass grafting or heart valve replacement) is an intervention aimed at relief of symptoms and increased wellbeing. It is a complex procedure with deep experiences encompassing physiological, psychological and social aspects. Health-care professionals' documentation of expressions of decreased wellbeing related to open heart surgery is an important basis for decisions and for the understanding of patients' overall health situation. METHOD: Eighty medical records were examined by means of qualitative and quantitative methods in order to explore documentation of patient wellbeing at four points in time. The analysis was performed by content analysis and descriptive statistics. RESULTS: Documentation of physical wellbeing was dominant on all occasions, while psychological wellbeing was moderately well documented and social aspects of wellbeing were rarely documented. CONCLUSION: The medical records did not adequately reflect the complexity of undergoing open heart surgery. Hence the holistic approach was not confirmed in health-care professionals' documentation. IMPLICATIONS FOR NURSING MANAGEMENT: Managers need to support and work for a patient-centred approach in cardiac care, resulting in patient documentation that reflects patient wellbeing as a whole.

Mirror therapy for Complex Regional Pain Syndrome (CRPS)-A literature review and an illustrative case report.

Background and purpose This case of a 42 year old woman with lower extremity Complex Regional Pain Syndrome (CRPS) after a twisting injury of the ankle, effectively treated with the addition of mirror therapy to a rehabilitation programme, prompted a literature review of both CRPS and mirror therapy. Mirror therapy is a newer adjunct to other forms of pain control and functional restoration for treatment of CRPS as well as other difficult clinical problems. This was a required group project as part of a university based course in chronic pain for healthcare workers. Materials and methods The PubMed database up to September 26,2012 was reviewed using four search word groups: "CRPS mirror therapy", "mirror CRPS", "reflex sympathetic dystrophy OR Complex Regional Pain Syndrome AND mirror" and "reflex sympathetic dystrophy OR Complex Regional Pain Syndrome AND mirror + RCT". Nine studies from PubMed met the criteria that this working group had chosen for inclusion in the analysis of mirror therapy as treatment. These references were supplemented by others on CRPS in order to generate an adequate review of both the syndrome CRPS and mirror therapy itself. Some references were specific for mirror therapy in the treatment of CRPS but others described mirror therapy for the treatment of phantom limb pain, brachial plexus avulsion pain, for physical rehabilitation of stroke related paresis and for rehabilitation after hand surgery. Results Criteria for the diagnosis of CRPS including the International Association for the Study of Pain criteria and the Budapest criteria are reviewed with an emphasis on the specificity and sensitivity of the various criteria for clinical and research purposes. The signs and symptoms of CRPS are a part of the criteria review. The main treatment strategy for CRPS is physical rehabilitation for return of function and mirror therapy is one of many possible strategies to aid in this goal. The patient in this case report had failed many of the adjunctive therapies and rehabilitation had been unsuccessful until the addition of mirror therapy. She then could progress with physical rehabilitation and return to a more normal life. Mirror therapy techniques are briefly described as part of a discussion of its success with relationship to signs and symptoms as well as to the duration of CRPS (and other syndromes). Some discussion of the theories of the central effects of both CRPS and phantom limb pain and how these are affected by mirror therapy is included. An analysis of the 9 most relevant articles plus a critique of each is present in table form for review. Conclusions There appears to be a clear indication for the use of mirror therapy to be included in the multidisciplinary treatment of CRPS types 1 and 2 with a positive effect on both pain and motor function. There is also evidence that mirror therapy can be helpful in other painful conditions such as post stroke pain and phantom limb pain. Implications CRPS is often overlooked as an explanation for obscure pain problems. Prompt diagnosis is essential for effective treatment. Mirror therapy is a newer technique, easy to perform and can be a useful adjunct to aid physical rehabilitation and decrease pain in this population. Much further prospective research on mirror therapy in CRPS is ongoing and is needed to systematize the technique, to clarify the effects and to define the place of this therapy in the multidisciplinary management of CRPS.

Electron-beam-initiated polymerization of poly(ethylene glycol)-based wood impregnants.

The current study demonstrates that methacrylate and acrylate poly(ethylene glycol) (PEG) functional oligomers can be effectively impregnated into wood blocks, and cured efficiently to high conversions without catalyst by e-beam radiation, allowing for less susceptibility to leaching, and favorable properties including higher Brinell hardness values. PEG based monomers were chosen because there is a long history of this water-soluble monomer being able to penetrate the cell wall, thus bulking it and decreasing the uptake of water which further protects the wood from fungal attack. Diacrylate, dimethacrylate, and dihydroxyl functional PEG of M(w) 550-575, of concentrations 0, 30, 60, and 100 wt % in water, were vacuum pressure impregnated into Scots Pine blocks of 15 × 25 × 50 mm in an effort to bulk the cell wall. The samples were then irradiated and compared with nonirradiated samples. It was shown by IR, DSC that the acrylate polymers were fully cured to much higher conversions than can be reached with conventional methods. Leaching studies indicated a much lower amount of oligomer loss from the cured vinyl functional PEG chains in comparison to hydroxyl functional PEG indicating a high degree of fastening of the polymer in the wood. The Brinell hardness indicated a significant increase in hardness to hardwood levels in the modified samples compared to the samples of hydroxyl functional PEG and uncured vinyl PEG samples, which actually became softer than the untreated Scots Pine. By monitoring the dimensions of the sample it was found by weight percent gain calculations (WPG %) that water helps to swell the wood structure and allow better access of the oligomers into the cell wall. Further, the cure shrinkage of the wood samples demonstrated infiltration of the oligomers into the cell wall as this was not observed for methyl methacrylate which is well-documented to remain in the lumen. However, dimensional stability of the vinyl polymer modified blocks when placed in water was not observed to the same extent as PEG.

Well-being in patients and relatives after open-heart surgery from the perspective of health care professionals.

AIM: The aim of this study was to explore how health care professionals perceive the well-being of patients and relatives following open-heart surgery. BACKGROUND: Open-heart surgery is an extraordinary life event associated with hope and fear among both patients and relatives, thus they require attention from health care professionals. Patients' short stay in hospital after surgery and the workload of health care professionals increase the risk that reduced well-being will be overlooked. Health care professionals need to become familiar with the signs of reduced well-being. DESIGN: The study has an observational design and was performed using a qualitative method. METHOD: Health care professionals working with patients who have undergone open-heart surgery participated in focus group discussions. The data were analysed by means of content analysis. RESULTS: Two categories emerged: signs of vulnerability and signs of insecurity. The latent meaning of the study was interpreted as awareness of an exposed position. CONCLUSION: The health care professionals were aware of patients' and relatives' exposed position following open-heart surgery. Reduced well-being was communicated by bodily and emotional signs, which were captured using direct communication or intuition. RELEVANCE TO CLINICAL PRACTICE: Developing the ability to recognise signs of reduced well-being is important for minimising the negative influences associated with open-heart surgery for patients and relatives. Increased awareness that both anger and avoidance can mask depression is important. Patients and their relatives, particularly younger ones, should be observed to ensure early detection of a life crisis provoked by the heart disease. Furthermore, staff should invite patients and their partners to talk about sexuality. Changes aimed at increasing patients' and relatives' well-being would be facilitated by interdisciplinary teamwork, 'reflection groups' for a greater exchange of knowledge and the implementation of a patient/family perspective. The latter would lead to greater interest in the relatives' situation and position in cardiac care.