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Artur Jędrzak,1,2 Bartosz F Grześkowiak,1 Klaudia Golba,1 Emerson Coy,1 Karol Synoradzki,1,3 Stefan Jurga,1 Teofil Jesionowski,2 Radosław Mrówczyński1 1NanoBioMedical Centre, Adam Mickiewicz University in Poznan, Poznan PL-61614, Poland; 2Institute of Chemical Technology and Engineering, Faculty of Chemical Technology, Poznan University of Technology, Poznan PL-60965, Poland; 3Institute of Molecular Physics Polish Academy of Sciences, Poznan PL-60179, PolandCorrespondence: Radosław MrówczyńskiNanoBioMedical Centre, Adam Mickiewicz University in Poznan, Wszechnicy Piastowskiej 3, Poznan PL-61614, PolandTel +48618296709Email radoslaw.mrowczynski@amu.edu.plIntroduction: We present a multimodal nanoplatforms for the treatment of hepatocellular carcinoma (HCC) in vitro. The nanoplatforms are based on polydopamine (PDA)-coated magnetite nanoparticles (NPs) and spheres (sMAG) with PAMAM dendrimers and functionalized with NHS-PEG-Mal (N-hydroxysuccinimide–polyethylene glycol–maleimide) linker, which allows their functionalization with a folic acid derivative. The nanomaterials bearing a folic acid-targeting moiety show high efficiency in killing cancer cells in the dual chemo- and photothermal therapy (CT-PTT) of the liver cancer cells in comparison to modalities performed separately.Materials and Methods: All materials are characterized in detail with transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential and magnetic measurements. Also, photothermal properties were determined under irradiation of nanoparticles with laser beam of 2 W/cm2. The nontoxicity of nanoparticles with doxorubicin and without was checked by WST and LIVE/DEAD assay. Those tests were also used to evaluate materials bearing folic acid and anticancer drug in combined chemo- and photothermal therapy of HCC. Further, the generation of reactive oxygen species profile was also evaluated using flow cytometry test.Results: Both NPs and sMAG showed high photothermal properties. Nevertheless, the higher photothermal response was found for magnetic spheres. Materials of concentration above 10 μg/mL reveal that their activity was comparable to free doxorubicin. It is worth highlighting that a functionalized magnetic sphere with DOXO more strongly affected the HepG2 cells than smaller functionalized nanoparticles with DOXO in the performed chemotherapy. This can be attributed to the larger size of particles and a different method of drug distribution. In the further stage, both materials were assessed in combined chemo- and photothermal therapy (CT-PTT) which revealed that magnetic spheres were also more effective in this modality than smaller nanoparticles.Conclusion: Here, we present two types of nanomaterials (nanoparticles and spheres) based on polydopamine and PAMAM dendrimers g.5.0 functionalized with NHS-PEG-Mal linker terminated with folic acid for in vitro hepatocellular carcinoma treatment. The obtained materials can serve as efficient agents for dual chemo- and photothermal therapy of HCC. We also proved that PDA-coated magnetic spheres were more efficient in therapies based on near-infrared irradiation because determined cell viabilities for those materials are lower than for the same concentrations of nanomaterials based on small magnetic nanoparticles.Keywords: magnetic nanoparticles, polydopamine, liver cancer, drug delivery

The consequences of myocardial infarction (MI) are an increasing problem worldwide. Despite spectacular progress in the invasive treatment of ischemic heart disease, the ability to limit the ischemia-reperfusion (I/R) injury remains largely unrealized. Recent studies have shown that stimulation of opioid receptors may confer a cardioprotective effect against I/R injury. Levosimendan, the inodilator, is indicated for the short-term treatment of acutely decompensated heart failure. We tested the hypothesis that levosimendan may provide cardioprotection in the opioid-like mechanism in the human myocardium.

Agnieszka Mlynarska,1,2 Rafal Mlynarski,2,3 Czeslaw Marcisz,1 Krzysztof S Golba2,3 1Department of Gerontology and Geriatric Nursing, School of Health Sciences, Medical University of Silesia, Katowice, Poland; 2Department of Electrocardiology, Upper Silesian Heart Centre, Katowice, Poland; 3Department of Electrocardiology and Heart Failure, School of Health Sciences, Medical University of Silesia, Katowice, PolandCorrespondence: Agnieszka MlynarskaDepartment of Gerontology and Geriatric Nursing, Upper-Silesian Medical Centre, ul. Ziolowa 45/47, Katowice 40-635, PolandFax +48 32 2524098Email mlynarska83@gmail.comIntroduction: Frailty is a common geriatric syndrome that causes an elevated risk of catastrophic declines in the health and function among older adults – we hypothesized that frailty may be related to the maintenance of sinus rhythm after cardioversion.Methods: The study sample was a group of 199 consecutive patients over 60 (average age 71.41 ± 6.99; 40.2% women) with AF who were hospitalized in order to perform electrical cardioversion. The Tilburg Frailty Indicator (TFI) was used to assess frailty before cardioversion. The six-month visit after the electrical cardioversion was a follow-up. The follow-up period for the maintenance of sinus rhythm after electrical cardioversion was 180 ± 14 days.Results: Patients in whom cardioversion was effective had a statistically significantly lower severity of frailty syndrome (3.44 ± 1.83 vs 5.87 ± 1.12; p=0.000) and its components: physical components (2.14 ± 1.33 vs 3.62 ± 1.05 p=0.000); emotional components (0.92 ± 0.79 vs 1.29 ± 0.86 p=0.037) and social components (0.37 ± 0.56 vs 0.96 ± 0.46; p=0.000) compared to those patients in which cardioversion was ineffective. In the logistic regression, frailty (OR: 0.65, 95% CI:0.5010– 0.8330; p=0.000) was observed to be an independent predictor for maintaining sinus rhythm.Conclusion: Frailty is a novel, independent factor that can be used to predict the effectiveness of electrical cardioversion and the maintenance of sinus rhythm in the elderly population. Modifying the level of recognition in the Tilburg Frailty Indicator to a 4 improved the prediction of the effectiveness of electrical cardioversion as well as the maintenance of sinus rhythm.Keywords: frailty, atrial fibrillation, electrical cardioversion, sinus rhythm

Agnieszka Mlynarska,1,2 Rafal Mlynarski,2,3 Czeslaw Marcisz,1 Krzysztof S Golba2,3 1Department of Gerontology and Geriatric Nursing, School of Health Sciences, Medical University of Silesia, Katowice, Poland; 2Department of Electrocardiology, Upper Silesian Heart Centre, Katowice, Poland; 3Department of Electrocardiology and Heart Failure, School of Health Sciences, Medical University of Silesia, Katowice, Poland Background: The response to cardiac resynchronization therapy (CRT) is an important element of the treatment of advanced heart failure, especially in the geriatric population. The aim of the study was to examine the impact of frailty syndrome on the response to treatment with CRT. Methods: Two hundred and forty-six patients of 60 years or older (aged 73.35±6.95; 22.4% women) with an implanted CRT were included in this single-center prospective study. There was a 12-month follow-up. The Tilburg Frailty Indicator was used to determine frailty (5 or more points). The response to CRT was evaluated based on an analysis of clinical criteria. Results: One hundred and sixty-nine of 246 (68.9%) patients were found to be clinical CRT responders. Frailty syndrome was recognized in 173 (70.32%). There were 63.0% responders in the frailty-affected group, whereas there were statistically more responders (79.5%) in the robust group (P=0.0116). In the logistic regression, frailty emerged as an independent predictor of the response to CRT (OR=0.81, 95% CI=0.71–0.92; P=0.0008). The area under the curve of the ROC curve for frailty in the responders to CRT was 0.62. The cut-off value for a designation of frailty was 6 (P=0.0014). Conclusion: Frailty is a novel independent factor that can be used to predict the clinical response to CRT in the elderly population. Modifying the level of recognition in the Tilburg Frailty Indicator can improve the prediction of a response to CRT. Keywords: cardiac resynchronization, frailty syndrome, heart failure, outcomes, responders

Agnieszka Mlynarska,1,2 Krzysztof S Golba,2,3 Rafal Mlynarski2 1Department of Internal Nursing, School of Health Sciences, Medical University of Silesia, Katowice, Poland; 2Department of Electrocardiology, Upper Silesian Heart Centre, Katowice, Poland; 3Department of Electrocardiology and Heart Failure, School of Health Sciences, Medical University of Silesia, Katowice, Poland Background: A thorough analysis of the capability for self-care in patients with heart failure (HF) reduces the frequency of hospitalizations that are caused by decompensation. The aim of the study was to assess the effect of the method of therapy for HF, the degree of the acceptance of illness, and the occurrence of frailty syndrome on adherence to the therapeutic recommendations and self-care in patients with HF.Methods: The study included 180 patients who were hospitalized after being diagnosed with HF. In all, we used the Polish versions of three validated instruments: the nine-item European Heart Failure Self-care Behavior Scale, Illness Acceptance Scale, and The Tilburg Frailty Indicator.Results: The capability for self-care of patients with HF was 27.8%. More than 65% of the patients followed the recommendations for taking medication and also followed a low-sodium diet, while only 5.5% of the patients followed the recommendations for physical exercise. Positive correlations were found between the capability for self-care and frailty syndrome and its components: general frailty components vs the capability for self-care: r=0.4449, P=0.0000; physical frailty components vs the capability for self-care: r=0.3974, P=0.0000; emotional frailty components vs the capability for self-care: r=0.2831, P=0.0001; social frailty components vs the capability for self-care: r=0.2180, P=0.0032, and a negative correlation between the capability for self-care and the degree of the acceptance of the illnesses (r=-0.4662, P=0.0000).Conclusion: A relatively low capability for self-care was found in patients with HF. The presence of frailty syndrome and a low level of the acceptance of illness are connected with a low capability for self-care. Keywords: self-care, heart failure, frailty, rehospitalization, acceptance of illness