Sub‐phenotyping Metabolic Disorders Using Body Composition: An Individualized, Nonparametric Approach Utilizing Large Data Sets

Objective This study performed individual-centric, data-driven calculations of propensity for coronary heart disease (CHD) and type 2 diabetes (T2D), utilizing magnetic resonance imaging-acquired body composition measurements, for sub-phenotyping of obesity and nonalcoholic fatty liver disease (NAFLD). Methods A total of 10,019 participants from the UK Biobank imaging substudy were included and analyzed for visceral and abdominal subcutaneous adipose tissue, muscle fat infiltration, and liver fat. An adaption of the k-nearest neighbors algorithm was applied to the imaging variable space to calculate individualized CHD and T2D propensity and explore metabolic sub-phenotyping within obesity and NAFLD. Results The ranges of CHD and T2D propensity for the whole cohort were 1.3% to 58.0% and 0.6% to 42.0%, respectively. The diagnostic performance, area under the receiver operating characteristic curve (95% CI), using disease propensities for CHD and T2D detection was 0.75 (0.73-0.77) and 0.79 (0.77-0.81). Exploring individualized disease propensity, CHD phenotypes, T2D phenotypes, comorbid phenotypes, and metabolically healthy phenotypes were found within obesity and NAFLD. Conclusions The adaptive k-nearest neighbors algorithm allowed an individual-centric assessment of each individual’s metabolic phenotype moving beyond discrete categorizations of body composition. Within obesity and NAFLD, this may help in identifying which comorbidities a patient may develop and consequently enable optimization of treatment

Neutrophil Trafficking in Pulmonary Inflammation: Monitoring Migration and Blockade with 111In-Labeled Leukocytes

AbstractAim: Although imaging of In vitro labeled leukocytes is commonly used for diagnosing inflammation and infection, data concerning the use of this technique to monitor neutrophil trafficking are scarce. Here we investigated thepotential of 111In-in vitro labeled leukocytes (InWBC) to monitor neutrophil trafficking in an animal model of pulmonary inflammation.Methods: F344 rats were divided into 3 groups: Controls (received only InWBC), Inflammation (intra-tracheally challenged with lipoteichoic acid (LTA)+peptidoglycan (PGN) two hours before InWBC injection), and Blockade(pulmonary challenge with receptor blockade [LTAPGN+Antileukinate, a CXC receptor 1 and 2 antagonist]). Leukocytes were obtained from donor rats and labeled with 111In-oxine using standard procedures. Labeling efficiencyand leukocyte integrity were determined. Animals were administered 3.7-4.6 MBq InWBC via the tail vein, and were imaged 18-30 hours later and then euthanized. Post mortem the lungs were lavaged and total and differential alveolar cell counts performed. Lung tissue myeloperoxidase (MPO) activity was determined. Lung, heart, liver, spleen, kidney, marrow, intestine, blood, and muscle were harvested and organ activity/gm tissue determined. Results: InWBC labeling efficiency and cell integrity were not significantly different among groups. InWBC pulmonary activity was significantly higher (p<0.0001) in the Inflammation group (17.10 ± 2.04%) than in the Controls (1.76 ± 0.60%) and the Blockade group (9.74 ± 1.14%). Hemocytometer assessment of the bronchoalveolar lavage fluid revealed that the total number of neutrophils was significantly higher in the Inflammation group than in Controls and the Blockade group. Pulmonary MPO activity (pg/mg tissue) was significantly higher (p<0.01) in the Inflammation group (14.11 ± 5.56%) than in Controls (5.22 ± 4.77%) and the Blockade group (3.66 ± 3.77%). InWBC splenic activity was significantly higher (p<0.0001) in the Controls than in the Inflammation and Blockade groups. In the remaining organs, InWBC activity was significantly higher in the Blockade group than in the Control and the Inflammation groups.Conclusions: In a rat model of pulmonary inflammation using Antileukinate to block neutrophil chemokine receptors, InWBC accurately characterized both pulmonary and extrapulmonary neutrophil trafficking. These data indicate that InWBC may be useful to monitor both pulmonary and extrapulmonary neutrophil trafficking associated with lung inflammation and its regulation

Magical attachment: Children in magical relations with hospital clowns

The aim of the present study was to achieve a theoretical understanding of several different-age children's experiences of magic relations with hospital clowns in the context of medical care, and to do so using psychological theory and a child perspective. The method used was qualitative and focused on nine children. The results showed that age was important to consider in better understanding how the children experienced the relation with the hospital clowns, how they described the magical aspects of the encounter and how they viewed the importance of clown encounters to their own well-being. The present theoretical interpretation characterized the encounter with hospital clowns as a magical safe area, an intermediate area between fantasy and reality. The discussion presented a line of reasoning concerning a magical attachment between the child and the hospital clowns, stating that this attachment: a) comprised a temporary relation; b) gave anonymity; c) entailed reversed roles; and d) created an emotional experience of boundary-transcending opportunities

Stable isotope records for the last 10 000 years from Okshola cave (Fauske, northern Norway) and regional comparisons

The sensitivity of terrestrial environments to past changes in heat transport is expected to be manifested in Holocene climate proxy records on millennial to seasonal timescales. Stalagmite formation in the Okshola cave near Fauske (northern Norway) began at about 10.4 ka, soon after the valley was deglaciated. Past monitoring of the cave and surface has revealed stable modern conditions with uniform drip rates, relative humidity and temperature. Stable isotope records from two stalagmites provide time-series spanning from c. 10 380 yr to AD 1997; a banded, multi-coloured stalagmite (Oks82) was formed between 10 380 yr and 5050 yr, whereas a pristine, white stalagmite (FM3) covers the period from ~7500 yr to the present. The stable oxygen isotope (&amp;delta;&lt;sup&gt;18&lt;/sup&gt;O&lt;sub&gt;c&lt;/sub&gt;), stable carbon isotope (&amp;delta;&lt;sup&gt;13&lt;/sup&gt;C&lt;sub&gt;c&lt;/sub&gt;), and growth rate records are interpreted as showing i) a negative correlation between cave/surface temperature and &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O&lt;sub&gt;c&lt;/sub&gt;, ii) a positive correlation between wetness and &amp;delta;&lt;sup&gt;13&lt;/sup&gt;C&lt;sub&gt;c&lt;/sub&gt;, and iii) a positive correlation between temperature and growth rate. Following this, the data from Okshola show that the Holocene was characterised by high-variability climate in the early part, low-variability climate in the middle part, and high-variability climate and shifts between two distinct modes in the late part. &lt;br&gt;&lt;br&gt; A total of nine Scandinavian stalagmite &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O&lt;sub&gt;c&lt;/sub&gt; records of comparable dating precision are now available for parts or most of the Holocene. None of them show a clear Holocene thermal optimum, suggesting that they are influenced by annual mean temperature (cave temperature) rather than seasonal temperature. For the last 1000 years, &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O&lt;sub&gt;c&lt;/sub&gt; values display a depletion-enrichment-depletion pattern commonly interpreted as reflecting the conventional view on climate development for the last millennium. Although the &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O&lt;sub&gt;c&lt;/sub&gt; records show similar patterns and amplitudes of change, the main challenges for utilising high-latitude stalagmites as palaeoclimate archives are i) the accuracy of the age models, ii) the ambiguity of the proxy signals, and iii) calibration with monitoring data

Body Composition Profiling in the UK Biobank Imaging Study

Objective To investigate the value of imaging-based multivariable body composition profiling by describing its association with coronary heart disease (CHD), type 2 diabetes (T2D), and metabolic health on individual and population levels. Methods The first 6,021 participants scanned by UK Biobank were included. Body composition profiles (BCPs) were calculated including abdominal subcutaneous adipose tissue, visceral adipose tissue (VAT), thigh muscle volume, liver fat, and muscle fat infiltration (MFI), determined using magnetic resonance imaging. Associations between BCP and metabolic status were investigated using matching procedures and multivariable statistical modelling. Results Matched control analysis showed higher VAT and MFI was associated with CHD and T2D (p<0.001). Higher liver fat was associated with T2D (p<0.001) and lower liver fat with CHD (p<0.05), matching on VAT. Multivariable modelling showed lower VAT and MFI was associated with metabolic health (p<0.001), liver fat was non-significant. Associations remained significant adjusting for sex, age, BMI, alcohol, smoking, and physical activity. Conclusions Body composition profiling enabled an intuitive visualization of body composition and showed the complexity of associations between fat distribution and metabolic status, stressing the importance of a multivariable approach. Different diseases were linked to different BCPs, which could not be described by a single fat compartment alone

Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors

<p>Abstract</p> <p>Background</p> <p>It has been well established that human fetuses will heal cutaneous wounds with perfect regeneration. Insulin-like growth factors are pro-fibrotic fibroblast mitogens that have important roles in both adult wound healing and during development, although their relative contribution towards fetal wound healing is currently unknown. We have compared responses to IGF-I and -II in human dermal fibroblast strains derived from early gestational age fetal (<14 weeks) and developmentally mature postnatal skin to identify any differences that might relate to their respective wound healing responses of regeneration or fibrosis.</p> <p>Results</p> <p>We have established that the mitogenic response of fetal cells to both IGF-I and -II is much lower than that seen in postnatal dermal fibroblasts. Further, unlike postnatal cells, fetal cells fail to synthesise collagen in response to IGF-I, whereas they do increase synthesis in response to IGF-II. This apparent developmentally regulated difference in response to these related growth factors is also reflected in changes in the tyrosine phosphorylation pattern of a number of proteins. Postnatal cells exhibit a significant increase in phosphorylation of ERK 1 (p44) in response to IGF-I and conversely the p46 isoform of Shc on IGF-II stimulation. Fetal cells however only show a significant increase in an unidentified 100 kDa tyrosine-phosphorylated protein on stimulation with IGF-II.</p> <p>Conclusion</p> <p>Dermal fibroblasts exhibit different responses to the two forms of IGF depending on their developmental maturity. This may relate to the developmental transition in cutaneous wound healing from regeneration to fibrosis.</p

Self-assembly-driven electrospinning:the transition from fibers to intact beaded morphologies

Polymer beads have attracted considerable interest for use in catalysis, drug delivery, and photo­nics due to their particular shape and surface morphology. Electrospinning, typically used for producing nanofibers, can also be used to fabricate polymer beads if the solution has a sufficiently low concentration. In this work, a novel approach for producing more uniform, intact beads is presented by electrospinning self-assembled block copolymer (BCP) solutions. This approach allows a relatively high polymer concentration to be used, yet with a low degree of entanglement between polymer chains due to microphase separation of the BCP in a selective solvent system. Herein, to demonstrate the technology, a well-studied polystyrene-poly(ethylene butylene)–polystyrene triblock copolymer is dissolved in a co-solvent system. The effect of solvent composition on the characteristics of the fibers and beads is intensively studied, and the mechanism of this fiber-to-bead is found to be dependent on microphase separation of the BCP

Identification of challenges to the availability and accessibility of opioids in twelve European countries:conclusions from two ATOME six-country workshops

Background: Access to many controlled medicines is inadequate in a number of European countries. This leads to deficits in the treatment of moderate to severe pain as well as in opioid agonist therapy. Objective: The study objective was to elaborate the reasons for this inadequacy. The work plan of the Access to Opioid Medication in Europe (ATOME) project included two six-country workshops. These workshops comprised a national situational analysis, drafting tailor-made recommendations for improvement and developing action plans for their implementation. Methods: In total, 84 representatives of the national Ministries of Health, national controlled substances authorities, experts representing regulatory and law enforcement authorities, leading health care professionals, and patient representatives from 13 European countries participated in either one of the workshops. The delegates used breakout sessions to identify key common challenges. Content analysis was used for the evaluation of protocols and field notes. Results: A number of challenges to opioid accessibility in the countries was identified in the domains of knowledge and educational, regulatory, legislative, as well as public awareness and training barriers that limit opioid prescription. In addition, short validity of prescriptions and bureaucratic practices resulting in overregulation impeded availablity of some essential medicines. Stigmatization and criminalisation of people who use drugs remained the major impediment to increasing opioid agonist program coverage. Conclusions: The challenges identified during outcomes of the workshops were used as the basis for subsequent dissemination and implementation activities in the ATOME project, and in some countries the workshop proceedings already served as a stepping-stone for the first changes in regulations and legislation

Barriers and facilitators for the use of NURSING bedside handovers : implications for evidence‐based practice

BACKGROUND: Previous studies on bedside handovers have identified nurse-related barriers and facilitators for implementing bedside handovers, but have neglected the existing ward's nursing care system as an important influencing factor. AIMS: To determine the association between the existing nursing care system (i.e., decentralized, two-tier, or centralized) on a ward and the barriers and facilitators of the bedside handover. METHODS: Structured individual interviews (N = 106) on 14 nursing wards in eight hospitals were performed before implementation of bedside handovers. The structured interview guide was based on a narrative review. Direct content analysis was used to determine the nursing care system of a ward and the degree to which barriers and facilitators were present. Pearson's Chi-square analysis was used to determine whether there were associations between the nursing care systems concerning the presence of barriers and facilitators for implementing bedside handovers. RESULTS: Twelve barriers and facilitators were identified, of which three are new to literature: the possible loss of opportunities for socializing, collegiality, and overview; head nurse's role; and role of colleagues. The extent to which barriers and facilitators were present differed across nursing care systems, with the exception of breach of confidentiality (barrier), and an existing structured handover (facilitator). Overall, nurses working in decentralized nursing care systems report fewer barriers against and more facilitators in favor of using bedside handovers than nurses in two-tier or centralized systems. LINKING EVIDENCE TO ACTION: Before implementing bedside handovers, the context of the nursing care system may be considered to determine the most effective process to implement change. Based on these study findings, implementing bedside handovers could be more challenging on wards with a two-tier or centralized care system