Bio-inspired pulmonary surfactant-modified nanogels : a promising siRNA delivery system

Inhalation therapy with small interfering RNA (siRNA) is a promising approach in the treatment of pulmonary disorders. However, clinical translation is severely limited by the lack of suitable delivery platforms. In this study, we aim to address this limitation by designing a novel bioinspired hybrid nanoparticle with a core-shell nanoarchitecture, consisting of a siRNA-loaded dextran nanogel (siNG) core and a pulmonary surfactant (Curosurf (R)) outer shell. The decoration of siNGs with a surfactant shell enhances the colloidal stability and prevents siRNA release in the presence of competing polyanions, which are abundantly present in biofluids. Additionally, the impact of the surfactant shell on the biological efficacy of the siNGs is determined in lung cancer cells. The presence of the surfactants substantially reduces the cellular uptake of siNGs. Remarkably, the lowered intracellular dose does not impede the gene silencing effect, suggesting a crucial role of the pulmonary surfactant in the intracellular processing of the nanoparticles. In order to surmount the observed reduction in cellular dose, folate is incorporated as a targeting ligand in the pulmonary surfactant shell to incite receptor-mediated endocytosis. The latter substantially enhances both cellular uptake and gene silencing potential, achieving efficient knockdown at siRNA concentrations in the low nanomolar range. (C) 2015 Elsevier B.V. All rights reserved

Using corporate stories to build the corporate brand: An impression management perspective

Purpose: A recent area of academic interest within corporate branding and reputation is the use of storytelling in order to differentiate the corporate brand, however there is little empirical research exploring the contents of corporate stories, and how they are used by organisations to build the corporate brand. This paper aims to utilise impression management theory to bring insight into the potential role of corporate stories in shaping the corporate brand. Design/methodology/approach: Corporate stories were identified from the web sites of 99 organisations in both the for-profit and not-for-profit sectors, and content analysis conducted on the stories, using a deductive approach to identify the story elements present in the stories. Findings: There are wide variations in the inclusion of different elements in the stories, indicating that organisations place greater importance on the inclusion of some elements in their corporate stories than others. Research limitations/implications: The paper highlights the point that while organisations are using corporate stories, they are not sufficiently leveraging them to build their corporate brand. There is a gap between storytelling theory and practice, in that the literature emphasises the importance of including benefits for stakeholders, emotion, and aspects of the corporate strategy in stories, whereas organisations frequently neglect these aspects and instead focus mainly on their accomplishments. Originality/value: This study has found impression management theory to be a useful perspective on exploring corporate storytelling, and identifies links between the elements of stories and impression management strategies and behaviours. This indicates that the corporate story could influence the impressions that audiences form of the organisation and therefore build the corporate brand. © Emerald Group Publishing Limited

Hornblendite delineates zones of mass transfer through the lower crust

Geochemical signatures throughout the layered Earth require significant mass transfer through the lower crust, yet geological pathways are under-recognized. Elongate bodies of basic to ultrabasic rocks are ubiquitous in exposures of the lower crust. Ultrabasic hornblendite bodies hosted within granulite facies gabbroic gneiss of the Pembroke Valley, Fiordland, New Zealand, are typical occurrences usually reported as igneous cumulate hornblendite. Their igneous features contrast with the metamorphic character of their host gabbroic gneiss. Both rock types have a common parent; field relationships are consistent with modification of host gabbroic gneiss into hornblendite. This precludes any interpretation involving cumulate processes in forming the hornblendite; these bodies are imposter cumulates. Instead, replacement of the host gabbroic gneiss formed hornblendite as a result of channeled high melt flux through the lower crust. High melt/rock ratios and disequilibrium between the migrating magma (granodiorite) and its host gabbroic gneiss induced dissolution (grain-scale magmatic assimilation) of gneiss and crystallization of mainly hornblende from the migrating magma. The extent of this reaction-replacement mechanism indicates that such hornblendite bodies delineate significant melt conduits. Accordingly, many of the ubiquitous basic to ultrabasic elongate bodies of the lower crust likely map the ‘missing’ mass transfer zones

High g-Force Rollercoaster Rides Induce Sinus Tachycardia but No Cardiac Arrhythmias in Healthy Children

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Theme park operators and medical professionals advise children with heart conditions against using rollercoaster rides, but these recommendations are not evidence-based. The underlying assumption is that the combination of adrenergic stimulation through stress and acceleration might trigger arrhythmias in susceptible individuals. We conducted a cross-sectional observational study to assess heart rate and rhythm in healthy children during commercial rollercoaster rides. Twenty healthy children (9 male) aged 11-15 (mean 13.3 ± 1.4) years underwent continuous heart rate and rhythm monitoring (2-lead ECG) from 5 min before until 10 min after each of 4 high speed (>50 km h(-1)), high g-force (>4) commercial rollercoaster rides. Total recording time was 13 h 20 min. No arrhythmic events were detected. Resting heart rate was 81 ± 10 b min(-1) and increased to 158 ± 20 b·min(-1) during rides. The highest mean HR (165 ± 23 b min(-1)) was observed on the ride with the lowest g-force (4.5 g), but one of the highest speeds (100 km h(-1)). Anticipatory tachycardia (126 ± 15 b min(-1)) within 5 min was frequently observed. A 10 min recovery HR (124 ± 17 b min(-1)) was 56 % greater than resting HR. The speed and g-force experienced on roller coasters induce sinus tachycardia but do not elicit pathological arrhythmias in healthy children.This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. Dr Pieles is the holder of an NIHR Academic Clinical Lectureship in Paediatric Cardiology. We would like to thank Novacor Ltd (Swanley, Kent, UK) for providing portable ECG monitoring equipment and Thorpe Park (Merlin Entertainments PLC, Poole, Dorset, UK) for their support during data acquisition. We thank all of the children and their families for participating in this study

Prevalence of Acanthosis Nigricans in an urban population in Sri Lanka and its utility to detect metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Insulin resistance (IR) plays a major role in the pathogenesis of metabolic syndrome. Acanthosis nigricans (AN) is an easily detectable skin condition that is strongly associated with IR. The aims of this study were, firstly, to investigate the prevalence of AN among adults in an urban Sri Lankan community and secondly, to describe its utility to detect metabolic syndrome.</p> <p>Findings</p> <p>In a community based investigation, 35-64 year adults who were selected using stratified random sampling, underwent interview, clinical examination, liver ultrasound scanning, and biochemical and serological tests. Metabolic syndrome was diagnosed on revised ATP III criteria for Asian populations. AN was identified by the presence of dark, thick, velvety skin in the neck.</p> <p>2957 subjects were included in this analysis. The prevalence of AN, metabolic syndrome and type 2 diabetes mellitus were 17.4%, 34.8% and 19.6%, respectively. There was a strong association between AN and metabolic syndrome. The sensitivity, specificity, positive predictive value and negative predictive value of AN to detect metabolic syndrome were 28.2%, 89.0%, 45.9% and 79.0% for males, and 29.2%, 88.4%, 65.6% and 62.3% for females, respectively.</p> <p>Conclusions</p> <p>AN was common in our study population, and although it did not have a high enough sensitivity to be utilized as a screening test for metabolic syndrome, the presence of AN strongly predicts metabolic syndrome.</p

Cochrane corner: Physical activity interventions for people with congenital heart disease

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordUniversity of ExeterCanon Medical Systems UK Ltd

The Role of Speckle Tracking Echocardiography in the Evaluation of Common Inherited Cardiomyopathies in Children and Adolescents: A Systematic Review

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Data available on request.Speckle tracking echocardiography (STE) has gained importance in the evaluation of adult inherited cardiomyopathies, but its utility in children is not well characterized. We conducted a systematic review to evaluate the role of STE in pediatric inherited cardiomyopathies. PubMed, EMBASE, Web of Science, Scopus, CENTRAL and CINAHL databases were searched up to May 2020, for terms related to inherited cardiomyopathies and STE. Included were dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular non-compaction (LVNC) and arrhythmogenic cardiomyopathy (ACM). A total of 14 cohorts were identified, of which six were in DCM, four in HCM, three in LVNC and one in ACM. The most commonly reported STE measurements were left ventricular longitudinal strain (Sl), circumferential strain (Sc), radial strain (Sr) and rotation/torsion/twist. Sl, Sc and were abnormal in all DCM and LVNC cohorts, but not in all HCM. Apical rotation and twist/torsion were increased in HCM, and decreased in LVNC. Abnormal STE parameters were reported even in cohorts with normal non-STE systolic/diastolic measurements. STE in childhood cardiomyopathies can detect early changes which may not be associated with changes in cardiac function detectable by non-STE methods. Longitudinal and circumferential strain should be introduced in the cardiomyopathy echocardiography protocol, reflecting current practice in adults.Medical Research Council (MRC)Majlis Amanah Rakyat (MARA)University of ExeterCanon Medical Systems UK Ltd

Leg disorders in broiler chickens : prevalence, risk factors and prevention

Broiler (meat) chickens have been subjected to intense genetic selection. In the past 50 years, broiler growth rates have increased by over 300% (from 25 g per day to 100 g per day). There is growing societal concern that many broiler chickens have impaired locomotion or are even unable to walk. Here we present the results of a comprehensive survey of commercial flocks which quantifies the risk factors for poor locomotion in broiler chickens.We assessed the walking ability of 51,000 birds, representing 4.8 million birds within 176 flocks.We also obtained information on approximately 150 different management factors associated with each flock. At a mean age of 40 days, over 27.6% of birds in our study showed poor locomotion and 3.3% were almost unable to walk. The high prevalence of poor locomotion occurred despite culling policies designed to remove severely lame birds from flocks. We show that the primary risk factors associated with impaired locomotion and poor leg health are those specifically associated with rate of growth. Factors significantly associated with high gait score included the age of the bird (older birds), visit (second visit to same flock), bird genotype, not feeding whole wheat, a shorter dark period during the day, higher stocking density at the time of assessment, no use of antibiotic, and the use of intact feed pellets. The welfare implications are profound. Worldwide approximately 261010 broilers are reared within similar husbandry systems.We identify a range of management factors that could be altered to reduce leg health problems, but implementation of these changes would be likely to reduce growth rate and production. A debate on the sustainability of current practice in the production of this important food source is required

The Role of Speckle-Tracking Echocardiography in Predicting Mortality and Morbidity in Patients With Congenital Heart Disease: A Systematic Review and Meta-analysis

This is the final version. Available on open access from Elsevier via the DOI in this recordData Availability Statement: The data underlying this article will be shared on reasonable request to the corresponding authorBACKGROUND: Speckle-tracking echocardiography (STE) is now routinely included in cardiac evaluations, but its role in predicting mortality and morbidity in congenital heart disease (CHD) is not well described. We conducted a systematic review to evaluate the prognostic value of STE in patients with CHD. METHODS: The EMBASE, Medline, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to January 2023 for terms related to all CHD, STE, and prognosis. Meta-analysis of association of right ventricle and left ventricle strain (RV Sl and LV Sl, respectively) with major adverse cardiovascular events (MACEs) was performed in atrial switch transposition of the great arteries (asTGA)/congenitally corrected TGA (ccTGA), tetralogy of Fallot (ToF), and congenital aortic stenosis (cAS)/bicuspid aortic valve (BAV). P-value combination analysis was additionally performed for all CHD groups. RESULTS: A total of 33 studies (30 cohorts, n = 8,619 patients, children, and adults) were included. Meta-analysis showed the following parameters as being associated with MACE: RV Sl in asTGA/ccTGA (hazard ratio [HR] = 1.1/%; CI, [1.03; 1.18]), RV Sl and LV Sl in ToF (HR = 1.14/%; CI, [1.03; 1.26] and HR = 1.14/%; CI, [1.08; 1.2], respectively), and LV Sl in cAS/BAV (HR = 1.19/%; CI, [1.15; 1.23]). The RV Sl and strain rate were associated with outcomes also in single ventricle/hypoplastic left heart syndrome (at all palliation stages except before Norwood stage 1) and LV Sl in Ebstein's anomaly. CONCLUSIONS: This systematic review and meta-analysis showed that biventricular strain and strain rate were associated with outcomes in a variety of CHD, highlighting the need for updated recommendations on the use of STE in the current guidelines, specific to disease types