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IntroductionSmall membrane particles called extracellular vesicles (EVs) transport biologically active cargo between cells, providing intercellular communication. The clinical application of EVs is limited due to the lack of scalable and cost-effective approaches for their production and purification, as well as effective loading strategies.MethodsHere we used EV mimetics produced by cell treatment with the actin-destabilizing agent cytochalasin B as an alternative to EVs for the delivery of therapeutic nucleic acids.ResultsCytochalasin-B-inducible nanovesicles (CINVs) delivered a fully modified N-(methanesulfonyl)- or mesyl (µ-) antisense oligonucleotide to B16 melanoma cells, selectively decreasing the level of target microRNA-21 with effectiveness comparable to that observed upon Lipofectamine 2000-mediated delivery. The efficiency of the CINV-mediated delivery of plasmid DNA encoding EGFP varied depending on the type of recipient cells. Surprisingly, under experimental conditions, CINVs were unable to deliver both modified and natural short RNA duplexes—small interfering RNA and immunostimulatory RNA—probably due to their poor loading into CINVs.DiscussionCINVs demonstrated unique properties for the delivery of therapeutic nucleic acids, especially for antisense oligonucleotide-based therapy.

Abstract Background As human activity alters the planet, there is a pressing need to understand how organisms adapt to environmental change. Of growing interest in this area is the role of epigenetic modifications, such as DNA methylation, in tailoring gene expression to fit novel conditions. Here, we reanalyzed nine invertebrate (Anthozoa and Hexapoda) datasets to validate a key prediction of this hypothesis: changes in DNA methylation in response to some condition correlate with changes in gene expression. Results In accord with previous observations, baseline levels of gene body methylation (GBM) positively correlated with transcription, and negatively correlated with transcriptional variation between conditions. Correlations between changes in GBM and transcription, however, were negligible. There was also no consistent negative correlation between methylation and transcription at the level of gene body methylation class (either highly- or lowly-methylated), anticipated under the previously described “seesaw hypothesis”. Conclusion Our results do not support the direct involvement of GBM in regulating dynamic transcriptional responses in invertebrates. If changes in DNA methylation regulate invertebrate transcription, the mechanism must involve additional factors or regulatory influences.

Objective. The aim of the present study is to typify BAEPs configurations of patients with different location of lesions caused by subarachnoid haemorrhage (SAH) and the ensuing complications, in view of assessing the auditory-brainstem system disturbance.Methods. The typization was performed by comparing BAEPs with standard patterns from two sets of types of BAEPs by ipsilateral and binaural stimulation and by cross-stimulation.Results. 94 BAEPs were used for collection of normal referential values: for the absolute latencies and the absolute amplitudes of waves I, II, III, IV and V; for inter-peak latencies I-III, II-III, III-V, I-V and II-V; for amplitude ratios I/V and III/V. 146 BAEPs of patients with mild SAH and 55 from patients with severe SAH, were typified. In 5 types of BAEPs out of a total of 11, the percentage of the potentials in patients with mild SAH and severe SAH differed significantly (p

The objective of this study is to examine the Bulgarian youths' mobility towards Europe. The investigation was carried out with 570 Bulgarian students. The data are presented as a questionnaire consisting of five parts. The first one deals with the motivations and is based on the Reversal Theory - predicting eight motivational states. The second part is based on the 2PAP theoretical model structuring the attitudes around four factors: Push, Pull, Anti Push and Anti Pull. The third one falls back on the Big Five Personality Test measuring five personality dimensions. And the concluding two parts are designed to obtain information about the degree of attraction and the intentions for mobility to the 25 destination countries of the European Union (EU). This has led to the hypothesis that a model of mobility exists based on these three theoretical models, as well as on emotional factors like attraction-repulsion to the country referred to. The hypothesis that was strongly supported by the statistical processing of the data will broaden our understanding of the youth's mobility. The present research is a part of a longitudinal study of the mobility intentions among young people. The investigation is of great interest from an educational, political and social point of view

In this study the metabolic network of cell energetics are investigated as a self-regulating system, the control which is described with non-classical variation method - the Bellman's equation (also known as a dynamic programming equation), on the basis of the thermodynamics of irreversible processes and the kinetics of the biochemical reactions.

A classification of intraoperative cardio-vascular complications (CVC) was performed, based on data from 466 patients subjected to emergency surgery, due to severe abdominal surgical diseases or traumas, in accordance with the severe criteria of ACC/AHA for CVC in noncardiac surgery. There were 370 intraoperative CVC registered, distributed as follows: groups with low risk (148), moderate risk (200), and high risk (22). Patient groups were formed, according to the CVC risk level, during the intraoperative period, for which the determinant factor for the group distribution of patients was the complication with the highest risk. Individual data was collected for each patient, based on 65 indices: age, physical status, diseases, surgical interventions, anaesthesiological information, intra and postoperative cardio-vascular complications, disease outcome, causes of death, cardiovascular disease anamnesis, anamnesis of all other nonsurgical diseases present, laboratory results, results from all imaging and instrumental examinations, etc. On the basis of these indices, a new distribution of the risk factors was implemented, into groups with different levels of risk of CVC during intraoperative period. This result is a solid argument, substantiating the proposal to introduce these adjustments for determining the severity of CVC in the specific conditions of emergency abdominal surgery.

A classification of intraoperative (IO) and postoperative (PO) cardio-vascular complications (CVC) was performed, based on data from 466 patients subjected to emergency surgery, due to severe abdominal surgical diseases or traumas, in accordance with the severe criteria of ACC/AHA in CVC for non-cardiac surgery. There were 370 intra and 405 postoperative (IO; PO) CVC registered, distributed as follows: groups with low risk (IO: 148; PO: 87), moderate risk (IO: 200; PO: 225), and high risk (IO: 22; PO: 93). Patient groups were formed, according to the CVC risk level, during the intra- and postoperative periods, for which the determinant factor for the group distribution of patients was the complication with the highest risk. Individual data was collected for each patient, based on 65 indices: age, physical status, diseases, surgical interventions, anaesthesiological information, intra and postoperative cardio-vascular complications, disease outcome, causes of death, cardio-vascular disease anamnesis, anamnesis of all other nonsurgical diseases present, laboratory results, results from all imaging and instrumental examinations, etc. The trend toward increase or decrease of the CVC risk was studied during the transition from intra- to the postoperative period. On the basis of these indices, a new distribution of the patients was implemented, into groups with different levels of risk of CVC during intra- and postoperative. This result is a solid argument, substantiating the proposal to introduce these adjustments to the ACC/AHA criteria for determining the severity of CVC in the specific conditions of emergency abdominal surgery.

The external electrical therapy of the heart requires the application of high voltage electrical pulses via large external electrodes, placed on selected locations on the thorax surface. The position of the electrodes is one of the major determinants of the transthoracic impedance (TTI), which influences the intracardiac current flow during electric shock and therefore affects the defibrillation success. The indefinite nature of the factors affecting TTI raised our interest in clinical study of the TTI behavior during long-term applications of the defibrillation pads in different positions on the patient's chest. The study involved 86 randomly selected patients (39 male and 49 female, age (20-83) years, height (150-190) cm, weight (50-110) kg, chest size (86-130) cm, 67 patients with normal skin, 13 patients with dry skin and 6 patients with greasy skin, 70 patients without and 16 patients with chest pilosity). TTI was measured by passing of a low-amplitude high-frequency (23 kHz) current between the two PADs (active area about 92 cm2). For each patient, the TTI was measured 10 s, 1 min and 5 min after sticking on the electrodes to the skin surface, separately for the two tested electrode positions - Position 1 (sub-clavicular/sub-axillar position) and Position 2 (antero-posterior position). TTI range is comparable for the two tested PAD positions - between 58 Ohm and 152 Ohm for Position 1 and between 55 Ohm and 149 Ohm for Position 2. TTI mean +/- SD value in Position 1 (107,2 +/- 22,3) Ohm is significantly higher than TTI in Position 2 (96,6 +/- 19,2) Ohm. Both the pilosity and the skin type do not change significantly the TTI value, however the patients with chest pilosity presented slightly higher TTI than those without pilosity. The TTI was higher for normal skin, followed by dry and greasy skin. TTI presented weak correlation with both the patient chest size and weight (r

Every intensive care unit (ICU) admits critically ill patients with disturbed vitally important functions. Time is a critical factor with such patients and the optimum behaviour of the medical team is decisive. They require optimised distribution of the staff and material resources, hence an adequate model of the structure and activities in an ICU is needed. Such a model was built using generalized nets (GNs). The workflow presented as a GNs-model is based on principles and prerequisites typical of ICU. Structure of the information included in the model: the updated information on the state of the ICU (occupancy rate of the hospital beds, the state of the patients, the available physicians and nurses, and their distribution for the concrete patients, available material facilities) is supported by specialised databases. There also exists a database of protocols with prescriptions for diagnostic and therapeutic conduct. The goal attained with GNs is: solution for the admission and servicing of patients at the ICU in a dynamically changing situation at any moment of the night and day. The dynamic workflow model in ICU in the form of a GNs is an adequate approach for optimum distribution of the resources and optimum conduct in the care for patients with severe disorders of the vital functions.