University of Kaposvár

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.

BACKGROUND AND PURPOSE: Aneurysm treatment by intrasaccular packing has been associated with a relatively high rate of recurrence. The use of mesh tubes has recently gained traction as an alternative therapy. This article summarizes the midterm results of using an endoluminal sleeve, the PED, in the treatment of aneurysms. MATERIALS AND METHODS: A total of 19 wide-neck aneurysms were treated in 18 patients: 10 by implantation of PEDs alone and 9 by a combination of PED and coils. Angiographic and clinical results were recorded immediately and at 6 months following treatment. RESULTS: Immediate angiographic occlusion was achieved in 4 and flow reduction, in another 15 aneurysms. Angiography at 6 months demonstrated complete occlusion in 17 and partial filling in 1 of 18 patients. There was no difference between coil-packed and unpacked aneurysms. Of 28 side branches covered by > or =1 device, the ophthalmic artery was absent immediately in 1 and at 6 months in another 2 cases. One patient experienced abrupt in-stent thrombosis resulting in a transient neurologic deficit, and 1 patient died due to rupture of a coexisting aneurysm. All giant aneurysms treated with PED alone were demonstrated by follow-up cross-sectional imaging to have involuted by 6 months. CONCLUSIONS: Treatment of large, wide-neck, or otherwise untreatable aneurysms with functional reconstruction of the parent artery may be achieved with relative safety using dedicated flow-modifying devices with or without adjunctive use of intrasaccular coil packing.

Abstract There is a constant need to increase productivity in aquaculture, particularly to improve growth rate, feed utilization as well as stress resistance of fish. Because of consumer concerns and strict regulations in many countries, the use of synthetic chemicals, hormones and antibiotics is becoming unviable and natural compounds are more acceptable to the public. A wide variety of chemical compounds are found in plants, and many of them have been shown to have beneficial effects on appetite, growth and the immune status of fish acting through different mechanisms. Phytochemicals contained in herbs may enhance the innate immune system, possess antimicrobial capabilities, and are redox active molecules with antioxidant characteristics that may help to improve the general physiological condition of fish. Many studies have discussed the values of phytochemicals as feed additives. Another paramount concern related to phytochemicals is their endocrine modulator effect that can be applied both in aquaculture targeting the production of table fish and the growing sector of ornamental fish production. Different mechanisms such as the effects at the steroid receptor level, effects on steroid synthesis, distribution and excretion, actions on the hypothalamus–pituitary–gonad axis, as well as indirect mechanisms including thyroid and growth hormone disruption have been postulated for the reproductive endocrine disruption in fish populations by phytochemicals. This paper reviews the results of a great number of studies focusing on phytochemicals such as essential oils, saponins, flavonoids and phytosterols discussing their effects on productive traits and the putative mechanism of action.

Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound's therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.

Abstract Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, characterized by a low platelet count (<100 × 10 9 /L) in the absence of other causes associated with thrombocytopenia. In most patients, IgG autoantibodies directed against platelet receptors can be detected. They accelerate platelet clearance and destruction, inhibit platelet production, and impair platelet function, resulting in increased risk of bleeding and impaired quality of life. Efgartigimod is a human IgG1 antibody Fc‐fragment, a natural ligand of the neonatal Fc receptor (FcRn), engineered for increased affinity to FcRn, while preserving its characteristic pH‐dependent binding. Efgartigimod blocks FcRn, preventing IgG recycling, and causing targeted IgG degradation. In this Phase 2 study, 38 patients were randomized 1:1:1 to receive four weekly intravenous infusions of either placebo (N = 12) or efgartigimod at a dose of 5 mg/kg (N = 13) or 10 mg/kg (N = 13). This short treatment cycle of efgartigimod in patients with ITP, predominantly refractory to previous lines of therapy, was shown to be well tolerated, and demonstrated a favorable safety profile consistent with Phase 1 data. Efgartigimod induced a rapid reduction of total IgG levels (up to 63.7% mean change from baseline), which was associated with clinically relevant increases in platelet counts (46% patients on efgartigimod vs 25% on placebo achieved a platelet count of ≥50 × 10 9 /L on at least two occasions, and 38% vs 0% achieved ≥50 × 10 9 /L for at least 10 cumulative days), and a reduced proportion of patients with bleeding. Taken together, these data warrant further evaluation of FcRn antagonism as a novel therapeutic approach in ITP.

AIMS: Cardiac miR-132 activation leads to adverse remodelling and pathological hypertrophy. CDR132L is a synthetic lead-optimized oligonucleotide inhibitor with proven preclinical efficacy and safety in heart failure (HF) early after myocardial infarction (MI), and recently completed clinical evaluation in a Phase 1b study (NCT04045405). The aim of the current study was to assess safety and efficacy of CDR132L in a clinically relevant large animal (pig) model of chronic heart failure following MI. METHODS AND RESULTS: In a chronic model of post-MI HF, slow-growing pigs underwent 90 min left anterior descending artery occlusion followed by reperfusion. Animals were randomized and treatment started 1-month post-MI. Monthly intravenous (IV) treatments of CDR132L over 3 or 5 months (3× or 5×) were applied in a blinded randomized placebo-controlled fashion. Efficacy was evaluated based on serial magnetic resonance imaging, haemodynamic, and biomarker analyses. The treatment regime provided sufficient tissue exposure and CDR132L was well tolerated. Overall, CDR132L treatment significantly improved cardiac function and reversed cardiac remodelling. In addition to the systolic recovery, diastolic function was also ameliorated in this chronic model of HF. CONCLUSION: Monthly repeated dosing of CDR132L is safe and adequate to provide clinically relevant exposure and therapeutic efficacy in a model of chronic post-MI HF. CDR132L thus should be explored as treatment for the broad area of chronic heart failure.

Magnetic resonance line scan diffusion imaging of the brain, with diffusion weighting between 5 and 5,000 sec/mm(2), was performed in healthy subjects and patients with a 1.5-T machine. For each voxel, biexponential signal decay fits produced two apparent diffusion constants and respective signal amplitudes. Images based on these parameters show potential for use in the differentiation of gray and white matter, edema, and tumor.

BACKGROUND: Porcine bone marrow-derived mesenchymal stem cells (MSCs) were stably transfected with a lentiviral vector for transgene expression of the trifusion protein renilla luciferase, red fluorescent protein and herpes simplex truncated thymidine kinase (LV-RL-RFP-tTK; positron emission tomography [PET] reporter gene) for in vivo noninvasive tracking of the intramyocardially delivered MSC fate. METHODS AND RESULTS: A closed-chest, reperfused myocardial infarction was created in farm pigs. Sixteen days after myocardial infarction, LV-RL-RFP-tTK-MSCs were injected intramyocardially using electromechanical mapping guidance in the infarct border zone (n=7). PET-computed tomographic metabolic and perfusion imaging was performed after an intravenous injection of 10 mCi [18F]-FHBG and 13N-ammonia PET at 30+/-2 hours and 7 days after LV-RL-RFP-tTK-MSC treatment. Fusion imaging of the [18F]-FHBG PET-computed tomography with MRI was used to determine the myocardial location of the injected LV-RL-RFP-tTK-MSCs. Seven days after injections, [18F]-FHBG PET showed a decreased cardiac uptake with a mild increased pericardial and pleura uptake in the treated animals, which was confirmed by the measurement of luciferase activity. At 10 days, infarct size by MRI in the LV-RL-RFP-tTK-MSC-treated animals was smaller than controls (n=7) (23.3+/-1.5% versus 30.2+/-3.5%, P<0.005). The presence of the LV-RL-RFP-tTK-MSCs (5.8+/-1.1% of the injected cells) in the myocardium 10 days after intramyocardial delivery was confirmed histologically. CONCLUSIONS: Reporter gene imaging enables the tracking of the persistence of viable LV-RL-RFP-tTK-MSC in the peri-infarcted porcine myocardium at 10 days after delivery using clinical PET scanners.

UNLABELLED: Postsurgically elevated or increasing serum calcitonin levels strongly suggest the presence of residual or recurrent medullary thyroid carcinoma (MTC). Several imaging modalities (sonography, MRI, CT, scintigraphy with different types of radiolabeled ligands, etc.) are routinely used in an attempt to localize tumorous tissue, but such efforts often fail. In the search for a more reliable method, 18F-FDG PET was applied to detect tumor tissue of residual or recurrent MTC. METHODS: Forty patients with a postoperatively elevated plasma calcitonin level were included. These patients underwent routine diagnostic imaging procedures (CT, MRI, and 131I-metaiodobenzylguanidine [MIBG] whole-body planar scintigraphy or SPECT) and 18F-FDG PET examinations. Two independent experts visually analyzed the images provided by each method to detect pathologic lesions. Lymph nodes of > or = 1 cm in short diameter that were detected by radiologic methods were considered to be pathologic. 18F-FDG accumulation with a sharp contour reported by both independent observers was similarly regarded as pathologic. RESULTS: PET detected 270 foci with a high tracer accumulation, whereas only 116 lesions were detected by MRI and 141 by CT. The numbers of such foci determined by PET, MRI, and CT were 98, 34, and 34, respectively, in the neck; 25, 5, and 6, respectively, in the supraclavicular regions; and 117, 35, and 39, respectively, in the mediastinum. 131I-MIBG scintigraphy findings were positive for only 3 patients. CONCLUSION: For MTC patients with a postoperatively elevated plasma tumor marker level, PET was more sensitive and superior in localizing tumorous lymph node involvement than were the other imaging modalities, especially in the cervical, supraclavicular, and mediastinal lymphatic regions.

Abstract Aim To investigate the phylogeographical patterns of red deer ( Cervus elaphus ) in Europe, and to disentangle the influence of ancient (e.g. Pleistocene ice ages) from more recent processes (e.g. human translocations). Location Europe. Methods In this study we provide by far the most extensive analysis of genetic structure in European red deer, based on analyses of variation at two mitochondrial markers (cyt b and D‐loop) in a large number of individuals from 39 locations. Relationships of mitochondrial DNA haplotypes were determined using minimum spanning networks and phylogenetic analyses. Population structure was examined by analyses of molecular variance. Historical processes shaping the present patterns were inferred from nested clade analysis and nucleotide diversity statistics. Results Within Europe, we detected three deeply divergent mitochondrial DNA lineages. The three lineages displayed a phylogeographical pattern dividing individuals into western European, eastern European and Mediterranean (Sardinia, Spain and Africa) groups, suggesting contraction into three separate refugia during the last glaciation. Few haplotypes were shared among these three groups, a finding also confirmed by F ST values. Calculations of divergence times suggest that the groups probably split during the Pleistocene. Main conclusions The observed pattern is interpreted to result from isolation in different refugia during the last glaciation. The western and eastern European lineages could be linked to an Iberian and Balkan refugium, respectively. The third lineage might originate from a Sardinian or African refugium. We link local phylogeographical patterns observed in Europe to the post‐glacial recolonization process, shaped by the geographical localization of refugia and barriers to gene flow. Regardless of the importance of red deer as a game species and the tradition of translocating red deer in Europe, we detected few individuals that did not match the trichotomous pattern, suggesting that translocations have occurred mainly at smaller spatial scales.

The feeding habits of feral domestic cats Felis catus (n=264), wild cats Felis silvestris (n=22) and their hybrids (n=30) were investigated in Hungary. Cat groups were identified taxonomically by morphological and molecular methods. Diet components were identified in stomach contents and faeces collected from the recta. In each cat group, abundant small mammals were dominant in the diet (relative frequency of occurrence: feral domestic cat, 61–82%, depending on regions; wild cat, 70%; hybrid, 59%). Birds were the second most important quarry (2–7%, 16% and 20%, respectively in the three cat groups), while the contribution of hares (1–2%, 5% and 3%, respectively) and other taxa was not significant. Every cat group preyed on small-sized animals (<50 g; 89–96%, 80% and 80%, respectively), terrestrial (91–98%, 84% and 86%, respectively) and wild (71–73%, 87% and 77%, respectively) prey. Standardized trophic niche breadth was typically very narrow (BA=0.07–0.16, 0.13 and 0.17, respectively). Feral domestic cats occasionally consumed household food (2–7%) and domestic animals (4–8%). This could mean that feral domestic cats have an advantage over wild cats that are food specialists. The trophic niche overlap between cat groups was high (77–88%). Food composition and feeding habits, (weight, zonation and environmental association of consumed prey) of feral domestic cats, however, was different compared to wild cats, which indicated the possibility of partial resource partitioning. The values for hybrids were between the two groups. As well as the stable presence of feral domestic cats (mean population density, D=1.34 individuals/1000 ha) based on field live-trapping, hybrids are also present (D=0.10), leading to continuous hybridization. This can threaten the population of wild cats, which are present at a low density (D=0.17).

The feeding ecology of the golden jackal ( Canis aureus L., 1758) and its interspecific trophic relationship with the sympatric red fox (Vulpes vulpes (L., 1758)) was investigated in an area of recent range expansion of the golden jackal in Hungary, central Europe. Diet composition was determined by scat analysis (over 4 years: jackal 814 scats; fox 894 scats). Compared with jackals, foxes consumed more small mammals (mean biomass consumed: jackal 77%; fox 68%) and to a lesser extent plant matter (6% and 18%, respectively). The importance of other prey, such as wild boar ( Sus scrofa L., 1758), cervids, brown hare ( Lepus europaeus Pallas, 1778), birds, reptiles, fish, invertebrates, and domestic animals, was minimal. Both mesocarnivores consumed primarily small animals (&lt;50 g: 92% and 87%, respectively); this implies a typical searching and solitary hunting strategy. The trophic niche breadth of both species was very narrow and the fox proved to be more of a generalist. The food overlap index between the two canids was high (mean, 73%) and varied with the decreasing availability and consumption of small mammals. Based on prey remains found in scats, small-mammal specialization over a 2-year period and seasonal predation upon wild boar piglets (mainly by the jackal), seasonal fruit eating (mainly by the fox), and scavenging on wild or domestic ungulates (both predators) were found.

This literature review focuses on the milk yield and milk composition of rabbits and the non-nutritional factors affecting both quantity and quality. Actual highly efficient hybrid does have an average daily milk yield of 250 g or 60 g/kg of live weight during the 4-weeks lactation period. However, compared with cow and sow milk, rabbit’s milk is much more concentrated in fat (12.9 g/100 g), protein (12.3 g/100 g) and energy (8.4 MJ/kg) which explains the extremely rapid growth of the young (weight × 6 after 3 weeks). Characteristic of rabbit milk is also the nearly absence of lactose (&lt;2 g/100 g). At peak lactation, protein output per kg metabolic weight (13.4 g/day/kg 0.75 ( exceeds even those of Holstein milk cows. The non-nutritional factors having the largest impact on the milk yield are the number of suckling kits, the parity order (primiparous vs. multiparous) and the gestation overlapping degree (rapid decline after 17-20 days of gestation). However, also through the reduction of feed intake, heat stress has a detrimental impact especially when the night temperature remains above 25°C. Rabbit milk lipids are highly saturated (70.4% SFA) due to the high content of C 8:0 – C 12:0 (50% of total FA) and further characterised by nearly equal quantities of oleic and linoleic acid and an w-6/w-3 ratio around 4. Finally some data about the amino acid, milk proteins including the immmunoglobulins, mineral and vitamin composition are presented.

Mannan oligosaccharides (MOSs) are often referred to as one of the potential alternatives for antimicrobial growth promoters. The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action based on the latest publications. We discuss the dietary impact of MOSs on (1) microbial changes, (2) morphological changes of gut tissue and digestibility of nutrients, and (3) immune response of pigs after weaning. Dietary MOSs maintain the intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period. Recent results suggest that MOS enhances the disease resistance in swine by promoting antigen presentation facilitating thereby the shift from an innate to an adaptive immune response. Accordingly, dietary MOS supplementation has a potential growth promoting effect in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards that are able to maintain a high growth rate after weaning.

OBJECTIVES: The aim of this preclinical study was to optimize the use of drug-eluting balloon (DEB) DIOR(2nd) (generation) by measurements of tissue and plasma paclitaxel concentrations in porcine coronary artery overstretch and prove efficacy in inhibition of neointimal growth without complementary use of stent. BACKGROUND: The usually recommended DEB 60 sec inflation time causes prolonged ischemia and arterial injury. METHODS: Tissue, plasma, and balloon surface concentrations of paclitaxel were measured in pigs 45 min and 12 hr after balloon inflation times of 15, 20, 30, 45, and 60 sec. Extent of neointimal hyperplasia was compared using DIOR(2nd) (generation) or noncoated balloon at two-week follow-up. Paclitaxel was replaced by fluorescent paclitaxel derivative in DEB and DES to demonstrate the distribution of the drug in arterial wall. RESULTS: DIOR(2nd) (generation) DEB provided 29 ± 3 μM/L, 52 ± 6 μM/L, 196 ± 44 μM/L, 202 ± 36 μM/L, and 184 ± 59 μM/L paclitaxel to the vessel wall after 15, 20, 30, 45, and 60 sec of dilation, reaching plateau at 30 sec inflation time. Paclitaxel penetrated up to 2 mm tissue deepness. Measurable plasma paclitaxel level (45 ± 28 ng/mL) was found only after 60 sec balloon inflation time. At follow-up, the dilated arterial segment neointimal area and maximal neointimal thickness were significantly smaller with DIOR vs. uncoated balloon use. Fluorescence images of DIOR showed a homogenous distribution of the drug on the vessel, in contrast with DES. CONCLUSION: Using the DIOR(2nd) (generation) DEB, a maximal balloon inflation time of 30-45 sec is optimal, reducing effectively the neointimal hyperplasia.

Nowadays sharing economy phenomenon is a popular topic among companies and academic researchers too. People share their intangible assets and underutilized tangible assets for money or for free with the help of the Internet which results in a new business model and creates a unique research area. The most popular expressions for this phenomenon are sharing economy and collaborative consumption; however, there are much more other definitions which refer to this. In order to new companies can enter and stabilize position on the market, they tend to use 'sharing economy' for their operation regardless of their business model which may mislead the customers. There is no clear agreement which is the only one definition that describes the sharing economy in the best way; there is a gap in the literature. For this reason, the purpose of this paper is to analyse the various expressions and make a clear difference between them. To achieve this goal, a systematic literature review has been carried out. According to the literature, 14 core definitions can be identified closely to sharing economy which means more or less the same; but not exactly the same. The result of this study shows how these are connected to each other and how their borders can be defined.

In this chapter, we will introduce small and medium-sized enterprises (SMEs) by defining and discussing characteristics of SMEs in qualitative and quantitative terms. In doing so, this chapter takes an international perspective to account for regional and international differences. As SMEs are often owner-managed, individual attitudes to management and decision-making play an important role in management and governance issues. Therefore, major research findings that contribute to a better understanding of the complex dependencies of SMEs from their owners are presented. Finally, we will address recent challenges and discuss how SMEs can address them to identify and exploit business opportunities.

Electrical impedance spectroscopy (EIS) is a useful tool for the investigation of the structural characteristics of solid materials and also biological tissues. The structural changes in plant or animal tissues reflect the physiological state of the organism. Electrical impedance measurement seems to be applicable both for analytical and research laboratories, since once a stress or a quality trait is correlated with an impedance parameter the method is quick and safe for further analysis of great number of samples. This work attempted to explore the current state of literature in terms of the application of EIS that has already been done on animal and plant tissues, and more specifically searching for the possibility of wider future applicability in plant stress detection.

The application of ionic liquids as solvents for the enantioselective esterification of (R,S)-2-chloropropanoic acid with butan-1-ol using Candida rugosa lipase is reported. The role of water produced during the reaction and controlling of the water activity with pervaporation was studied. The enantioselective esterification of (R,S)-2-chloropropanoic acid with butan-1-ol in different organic solvents and ionic liquids was studied. The reaction was effectively catalysed by Candida rugosa lipase. From the ionic solvents investigated, the best results were achieved in [bmim]PF6. The presence of water had a strong effect on the activity of the lipase. Since in esterification reactions with acid and alcohol equimolar amounts of water are formed, the excess of water was removed and the water activity was kept constant using a pervaporation system without any additives. At the optimum water activity Candida rugosa lipase showed high thermal stability in [bmim]PF6 and it could be reused for at least five recycles with only a small lost of activity.

It is generally believed that the apparent diffusion coefficient (ADC) changes measured by diffusion-weighted imaging (DWI) in brain pathologies are related to alterations in the water compartments. The aim of this study was to elucidate the role of compartmentalization in DWI via biexponential analysis of the signal decay due to diffusion. DWI experiments were performed on mouse brain over an extended range of b-values (up to 10,000 mm(-2) s) under intact, global ischemic, and cold-injury conditions. DWI was additionally applied to centrifuged human erythrocyte samples with a negligible extracellular space. Biexponential signal decay was found to occur in the cortex of the intact mouse brain. During global ischemia, in addition to a drop in the ADC in both components, a shift from the volume fraction of the rapidly diffusing component to the slowly diffusing one was observed. In cold injury, the biexponential signal decay was still present despite the electron-microscopically validated disintegration of the membranes. The biexponential function was also applicable for fitting of the data obtained on erythrocyte samples. The results suggest that compartmentalization is not an essential feature of biexponential decay in diffusion experiments.