Fast, quantitative, murine cardiac ¹⁹F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T

Purpose: To a) achieve cardiac ¹⁹F-Magnetic Resonance Imaging (MRI) of perfluoro-crown-ether (PFCE) labeled cardiac progenitor stem cells (CPCs) and bone-derived bone marrow macrophages, b) determine label concentration and cellular load limits, and c) achieve spectroscopic and image-based quantification. Methods: Theoretical simulations and experimental comparisons of spoiled-gradient echo (SPGR), rapid acquisition with relaxation enhancement (RARE), and steady state at free precession (SSFP) pulse sequences, and phantom validations, were conducted using ¹⁹F MRI/Magnetic Resonance Spectroscopy (MRS) at 9.4 T. Successful cell labeling was confirmed using flow cytometry and confocal microscopy. For CPC and macrophage concentration quantification, in vitro and post-mortem cardiac validations were pursued with the use of the transfection agent FuGENE. Feasibility of fast imaging is demonstrated in murine cardiac acquisitions in vivo, and in post-mortem murine skeletal and cardiac applications. Results: SPGR/SSFP proved favorable imaging sequences yielding good signal-to-noise ratio values. Confocal microscopy confirmed heterogeneity of cellular label uptake in CPCs. ¹⁹F MRI indicated lack of additional benefits upon label concentrations above 7.5–10 mg/ml/million cells. The minimum detectable CPC load was ~500k (~10k/voxel) in two-dimensional (2D) acquisitions (3–5 min) using the butterfly coil. Additionally, absolute ¹⁹F based concentration and intensity estimates (trifluoroacetic-acid solutions, macrophages, and labeled CPCs in vitro and post-CPC injections in the post-mortem state) scaled linearly with fluorine concentrations. Fast, quantitative cardiac ¹⁹F-MRI was demonstrated with SPGR/SSFP and MRS acquisitions spanning 3–5 min, using a butterfly coil. Conclusion: The developed methodologies achieved in vivo cardiac ¹⁹F of exogenously injected labeled CPCs for the first time, accelerating imaging to a total acquisition of a few minutes, providing evidence for their potential for possible translational work

In Vivo Tracking and 1H/19F Magnetic Resonance Imaging of Biodegradable Polyhydroxyalkanoate / Polycaprolactone Blend Scaffolds Seeded with Labeled Cardiac Stem Cells

Medium-chain length Polyhydroxyalkanoates (MCL-PHAs) have demonstrated exceptional properties for cardiac tissue engineering (CTE) applications. Despite prior work on MCL-PHA/Polycaprolactone (PCL) blends, optimal scaffold production and use as an alternative delivery route for controlled release of seeded cardiac progenitor cells (CPCs) in CTE applications in vivo has been lacking, We present herein applicability of MCL-PHA/PCL (95/5 wt%) blends fabricated as thin films with an improved performance compared to the neat MCL-PHA aiming to a) benefit from the material properties of natural and synthetic polymers, b) achieve controlled delivery and increase retention of delivered cells to the murine myocardium, c) extend the temporal window over which the release of labeled CPCs occurs compared to traditional direct injection techniques, and d) use 19F MRI/MRS to noninvasively detect, and longitudinally monitor the seeded scaffolds. Polymer characterization confirmed the chemical structure and composition of the synthesized scaffolds, while thermal, wettability, and mechanical properties were also investigated and compared in neat and porous counterparts. In vitro cytocompatibility studies were performed using perfluorocrown-ether (PFCE)-nanoparticle-labeled murine cardiac progenitor cells (CPC), and studied using confocal microscopy and 19F MRS/MRI. Seeded scaffolds were implanted and studied in the post-mortem murine heart in situ, and in two additional C57BL/6 mice in vivo (using single-layered and double-layered scaffolds) and imaged immediately after and at 7 days post-implantation. Superior MCL-PHA/PCL scaffold performance has been demonstrated compared to MCL-PHA through experimental comparisons of a) morphological data using scanning electron microscopy and b) contact angle measurements attesting to improved CPC adhesion, c) in vitro confocal microscopy showing increased SC proliferative capacity, d) mechanical testing that elicited good overall responses. In vitro MRI results justify the increased seeding density, increased in vitro MRI signal, and improved MRI visibility in vivo, in the double-layered compared to the single-layered scaffolds. Histological evaluations (bright-field, cytoplasmic (Atto647) and nuclear (DAPI) stains) performed in conjunction with confocal microscopy imaging attest to CPC binding within the scaffold, subsequent release and migration to the neighboring myocardium, and to increased retention in the murine myocardium in the case of the double-layered scaffold. Thus MCL-PHA/PCL blends possess tremendous potential for controlled delivery of CPCs and to maximize possible regeneration in myocardial infarction

Improving health and well-being through community health champions: a thematic evaluation of a programme in Yorkshire and Humber.

AIMS: The contribution that lay people can make to the public health agenda is being increasingly recognised in research and policy literature. This paper examines the role of lay workers (referred to as 'community health champions') involved in community projects delivered by Altogether Better across Yorkshire and Humber. The aim of the paper is to describe key features of the community health champion approach and to examine the evidence that this type of intervention can have an impact on health. METHODS: A qualitative approach was taken to the evaluation, with two strands to gathering evidence: interviews conducted with different stakeholder groups including project leads, key partners from community and statutory sectors and community workers, plus two participatory workshops to gather the views of community health champions. Seven projects (from a possible 12) were identified to be involved in the evaluation. Those projects that allowed the evaluation team to explore fully the champion role (training, infrastructure, etc.) and how that works in practice as a mechanism for empowerment were selected. In total, 29 semi-structured interviews were conducted with project staff and partners, and 30 champions, varying in terms of age, gender, ethnicity and disability, took part in the workshops. RESULTS: Becoming a community health champion has health benefits such as increased self-esteem and confidence and improved well-being. For some champions, this was the start of a journey to other opportunities such as education or paid employment. There were many examples of the influence of champions extending to the wider community of family, friends and neighbours, including helping to support people to take part in community life. Champions recognised the value of connecting people through social networks, group activities, and linking people into services and the impact that that had on health and well-being. Project staff and partners also recognised that champions were promoting social cohesiveness and helping to integrate people into their community. CONCLUSIONS: The recent public health White Paper suggested that the Altogether Better programme is improving individual and community health as well as increasing social capital, voluntary activity and wider civic participation. This evaluation supports this statement and suggests that the community health champion role can be a catalyst for change for both individuals and communities

Protection and Identification of Stateless Persons Through EU Law

A number of recent studies confirm that statelessness is a widespread phenomenon in the EU, which is not receiving adequate attention. The lack of well-functioning statelessness determination procedures is at the root of many problems associated with statelessness in the EU. These are, in particular, the inadequate protection of stateless persons and deficiencies in the prevention and reduction of statelessness. This paper argues in favour of common EU action on the identification and protection of stateless persons by analyzing the EU competence to pass relevant legislation, and explaining the desirability for such legislation

WACCM-D Whole Atmosphere Community Climate Model with D-region ion chemistry

Energetic particle precipitation (EPP) and ion chemistry affect the neutral composition of the polar middle atmosphere. For example, production of odd nitrogen and odd hydrogen during strong events can decrease ozone by tens of percent. However, the standard ion chemistry parameterization used in atmospheric models neglects the effects on some important species, such as nitric acid. We present WACCM-D, a variant of the Whole Atmosphere Community Climate Model, which includes a set of lower ionosphere (D-region) chemistry: 307 reactions of 20 positive ions and 21 negative ions. We consider realistic ionization scenarios and compare the WACCM-D results to those from the Sodankylä Ion and Neutral Chemistry (SIC), a state-of-the-art 1-D model of the D-region chemistry. We show that WACCM-D produces well the main characteristics of the D-region ionosphere, as well as the overall proportion of important ion groups, in agreement with SIC. Comparison of ion concentrations shows that the WACCM-D bias is typically within ±10% or less below 70 km. At 70–90 km, when strong altitude gradients in ionization rates and/or ion concentrations exist, the bias can be larger for some groups but is still within tens of percent. Based on the good agreement overall and the fact that part of the differences are caused by different model setups, WACCM-D provides a state-of-the-art global representation of D-region ion chemistry and is therefore expected to improve EPP modeling considerably. These improvements are demonstrated in a companion paper by Andersson et al

Genetic susceptibility to burnout in a Swedish twin cohort

Most previous studies of burnout have focused on work environmental stressors, while familial factors so far mainly have been overlooked. The aim of the study was to estimate the relative importance of genetic influences on burnout (measured with Pines Burnout Measure) in a sample of monozygotic (MZ) and dizygotic (DZ) Swedish twins. The study sample consisted of 20,286 individuals, born 1959–1986 from the Swedish twin registry who participated in the cross-sectional study of twin adults: genes and environment. Probandwise concordance rates (the risk for one twin to be affected given that his/her twin partner is affected by burnout) and within pair correlations were calculated for MZ and DZ same—and opposite sexed twin pairs. Heritability coefficients i.e. the proportion of the total variance attributable to genetic factors were calculated using standard biometrical model fitting procedures. The results showed that genetic factors explained 33% of the individual differences in burnout symptoms in women and men. Environmental factors explained a substantial part of the variation as well and are thus important to address in rehabilitation and prevention efforts to combat burnout

Durable Vision Improvement After a Single Intravitreal Treatment With Antisense Oligonucleotide in CEP290-Lca: Replication in Two Eyes

PURPOSE: An intravitreally injected antisense oligonucleotide, sepofarsen, was designed to modulate splicing within retinas of patients with severe vision loss due to deep intronic c.2991 + 1655A \u3e G variant in the OBSERVATIONS: Visual function was evaluated with best corrected standard and low-luminance visual acuities, microperimetry, dark-adapted chromatic perimetry, and full-field sensitivity testing. Retinal structure was evaluated with OCT imaging. At the fovea, all visual function measures and IS/OS intensity of the OCT showed transient improvements peaking at 3-6 months, remaining better than baseline at ∼2 years, and returning to baseline by 3-4 years after each single injection. CONCLUSIONS AND IMPORTANCE: These results suggest that sepofarsen reinjection intervals may need to be longer than 2 years

Teaching Mindfulness to Teachers: a Systematic Review and Narrative Synthesis

School teachers report high levels of stress which impact on their engagement with pupils and effectiveness as a teacher. Early intervention or prevention approaches may support teachers to develop positive coping and reduce the experience and impact of stress. This article reviews research on one such approach: mindfulness-based interventions (MBIs) for school teachers. A systematic review and narrative synthesis were conducted for quantitative and qualitative studies that report the effects of MBIs for teachers of children aged 5– 18 years on symptoms of stress and emotion regulation and self-efficacy. Twelve independent publications were identified meeting the inclusion criteria and these gave a total of 13 samples. Quality appraisal of the identified articles was carried out. The effect sizes and proportion of significant findings are reported for relevant outcomes. The quality of the literature varied, with main strengths in reporting study details, and weaknesses including sample size considerations. A range of MBIs were employed across the literature, ranging in contact hours and aims. MBIs showed strongest promise for intermediary effects on teacher emotion regulation. The results of the review are discussed in the context of a model of teacher stress. Teacher social and emotional competence has implications for pupil wellbeing through teacher–pupil relationships and effective management of the classroom. The implications for practice and research are considered

A systematic review of task- shifting for HIV treatment and care in Africa

BACKGROUND: Shortages of human resources for health (HRH) have severely hampered the rollout of antiretroviral therapy (ART) in sub-Saharan Africa. Current rollout models are hospital- and physician-intensive. Task shifting, or delegating tasks performed by physicians to staff with lower-level qualifications, is considered a means of expanding rollout in resource-poor or HRH-limited settings. METHODS: We conducted a systematic literature review. Medline, the Cochrane library, the Social Science Citation Index, and the South African National Health Research Database were searched with the following terms: task shift*, balance of care, non-physician clinicians, substitute health care worker, community care givers, primary healthcare teams, cadres, and nurs* HIV. We mined bibliographies and corresponded with authors for further results. Grey literature was searched online, and conference proceedings searched for abstracts. RESULTS: We found 2960 articles, of which 84 were included in the core review. 51 reported outcomes, including research from 10 countries in sub-Saharan Africa. The most common intervention studied was the delegation of tasks (especially initiating and monitoring HAART) from doctors to nurses and other non-physician clinicians. Five studies showed increased access to HAART through expanded clinical capacity; two concluded task shifting is cost effective; 9 showed staff equal or better quality of care; studies on non-physician clinician agreement with physician decisions was mixed, with the majority showing good agreement. CONCLUSIONS: Task shifting is an effective strategy for addressing shortages of HRH in HIV treatment and care. Task shifting offers high-quality, cost-effective care to more patients than a physician-centered model. The main challenges to implementation include adequate and sustainable training, support and pay for staff in new roles, the integration of new members into healthcare teams, and the compliance of regulatory bodies. Task shifting should be considered for careful implementation where HRH shortages threaten rollout programmes