Purpose Mesenchymal stromal cells (MSC) are an attractive tool for treatment of diabetic cardiomyopathy. Syndecan‐2/CD362 has been identified as a functional marker for MSC isolation. Imaging mass spectrometry (IMS) allows for the characterization of therapeutic responses in the left ventricle. This study aims to investigate whether IMS can assess the therapeutic effect of CD362 + ‐selected MSC on early onset experimental diabetic cardiomyopathy. Experimental Design 1 × 10 6 wild type (WT), CD362 − , or CD362 + MSC are intravenously injected into db/db mice. Four weeks later, mice are hemodynamically characterized and subsequently sacrificed for IMS combined with bottom‐up mass spectrometry, and isoform and phosphorylation analyses of cardiac titin. Results Overall alterations of the cardiac proteome signatures, especially titin, are observed in db/db compared to control mice. Interestingly, only CD362 + MSC can overcome the reduced titin intensity distribution and shifts the isoform ratio toward the more compliant N2BA form. In contrast, WT and CD362 − MSCs improve all‐titin phosphorylation and protein kinase G activity, which is reflected in an improvement in diastolic performance. Conclusions and Clinical Relevance IMS enables the characterization of differences in titin intensity distribution following MSC application. However, further analysis of titin phosphorylation is needed to allow for the assessment of the therapeutic efficacy of MSC.
A Magyar Közgazdasági Társaság Fejlődésgazdaságtani Szakosztálya interjút készített dr. Kovács Árpáddal, a Költségvetési Tanács elnökével, a Magyar Közgazdasági Társaság örökös tiszteletbeli elnökével a 2023-as költségvetésről a gazdaságpolitikai kihívások fényében. Az interjút 2022. augusztus 31-én zártuk le.
Background and Purpose The small molecule BGP‐15 has been reported to alleviate symptoms of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP‐15 in a rabbit model of atherosclerotic cardiomyopathy. Experimental Approach Rabbits were maintained on standard chow (control) or atherogenic diet (hypercholesterolemic) for 16 weeks. BGP‐15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium‐dependent vasorelaxation was assessed and key molecules in the protein kinase G (PKG) pathway were examined by enzyme‐linked immunosorbent assay (ELISA) and western blot. Passive force generation was investigated in skinned cardiomyocytes. Key Results Both acute and chronic BGP‐15 treatments improved the diastolic performance of the diseased heart. However, vasorelaxation and serum lipid markers were unaffected. Myocardial cyclic guanosine monophosphate (cGMP) levels were elevated in the BGP‐15‐treated group, along with preserved PKG activity and increased phospholamban Ser16‐phosphorylation. PDE5 expression decreased in the BGP‐15‐treated group and PDE1 was inhibited. Cardiomyocyte passive tension reduced in BGP‐15‐treated rabbits, the ratio of titin N2BA/N2B isoforms increased and PKG‐dependent N2B‐titin phosphorylation elevated. Conclusions and Implications BGP‐15 treatment improves diastolic function, reduces cardiomyocyte stiffness and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP‐PKG pathway. As BGP‐15 has been proven to be safe, it may be clinically useful in the treatment of diastolic dysfunction.
The continuous need towards improving the capacity of magnetic storage devices requires materials with strong perpendicular magnetic anisotropy. FePd, CoPd and their Co(Fe)Pt counterparts very attractive candidate for such purposes. The magnetic properties of these films are largely dependent on the orientation and local distribution of the L10 FePd phase fraction which are mainly controlled by diffusion processes and involve diffusion paths of a few angstroms. Highly ordered as well as disordered epitaxial isotope-periodic 57FePd/natFePd (001) thin films were prepared by molecular-beam epitaxy on MgO(001) substrate. Short range diffusion of different phases in FePd thin film induced by room temperature 130 keV He+ irradiation was investigated at fluences up to 30\times1015 ions/cm2. Conversion electron M\"ossbauer spectroscopy and synchrotron M\"ossbauer reflectivity experiments showed that the inter-atomic diffusion across 57FePd/natFePd interface occur mainly via the iron rich regions. The ratio of the diffusion length in the L10, fcc and iron rich structure are 1:1.4:5.6 respectively. Assuming that the diffusion coefficient in the fcc phase is between the diffusion coefficient of the L10 phase in the crystallographic c direction and perpendicular to it, the diffusion coefficient in the c-direction of the L10 phase is found more than 1.9 times lower than in the a-b plane.
OnkoNetwork is a recently established integrated care model with a personalized pathway system to manage patients with first suspect of a solid tumour in secondary care, that evolved as a regional initiative in Hungary. The primary aim of OnkoNetwork is the improvement of clinical outcomes via timely access to quality assured and defragmented healthcare services. The Horizon 2020 funded SELFIE project has selected OnkoNetwork for in-depth qualitative and quantitative evaluation. The aim of this study was to provide a qualitative evaluation of OnkoNetwork along the six components of the SELFIE conceptual framework: 1) service delivery, 2) leadership and governance, 3) workforce, 4) financing, 5) technologies and medical products, and 6) information and research. Analysis of published and grey programme documentation, followed by 20 semi-structured interviews with representatives of programme initiators, general and financial managers, involved physicians and non-physician professionals, patients and their informal caregivers. Transcripts of all interviews were analysed by Mayring's content analysis method by two independent researchers. This study yielded the first comprehensive description of the programme. OnkoNetwork is a blue dahila in Central and Eastern Europe, providing timely and quality-assured healthcare services for the target patients by personalized patient path monitoring and management in a financially sustainable manner without macro-level financing of its operation. Innovative professional roles were implemented for non-physicians and physicians, and a supporting information technology application was developed. This paper provides a systematic description of OnkoNetwork on the six components of the SELFIE conceptual framework for integrated care in multimorbidity to understand how and why OnkoNetwork was implemented and cares (better) for its patients. Because integrated care models are designed and adjusted to their specific local needs and context, those few successful and sustainable models that were established in Central and Eastern European countries represent important benchmarks for other initiatives in this region. Experience with OnkoNetwork during its planning, implementation and operation including the description of key success factors and barriers as perceived by various stakeholder groups, may support the development of further integrated care models especially in countries with similar economic status and healthcare settings.
