Global business companies' ethical behaviour: Universalism vs relativism

In the context of globalization, managing an organization affects communities, citizens and customers, employees, and different civil society associations. It concerns awareness of choices which managers make and that affect people's lives. The article examines how to deal with such situations in terms of universalism and relativism in international management, with the accompanying benefits and criticisms of each one. It also presents conveying the impact of organizations' activities in the daily lives of diverse populations around the world is, whose interests or even existence may at great extent be absent from the organization's decision-making. Measures for fostering ethical behaviour are also presented, respectively at international, national, community and intra-company levels. At the finale, we also highlight the main concerns about "best" rules and their applicability

Female expatriates’ barriers – myths and reality

Sending expatriates on international assignments today continues to be a serious challenge for organizations. Alongside the growing need for overseas employees, women are still under-represented (or even discriminated) compared to men. And while both men and women are capable of performing the various aspects of international job, there are additional challenges for the latter. The article examines the main barriers for women to get an international assignment. Basic myths about the reluctance of women due to the presence of family and "dual careers", as well as objective reasons such as the "glass ceiling" in the organization, are discussed. At the end, possible ways to overcome the barriers are presented

Unethical labour practices in MNEs' business worldwide

The article considers the emerging unethical cases in multinational companies' business worldwide  regarding the right to work and its dimensions. They refer to working conditions, the availability of child labor, discrimination in pay and employment, as well as regarding attitude towards women and girls. Specific cases about Bulgaria and Europe are elaborated.  Finally, measures taken by different stakeholders to minimize or eliminate the practices discussed are presented

Opportunities for financing Bulgarian cultural organizations (chitalishta)

Cultural resources are enormous, they are renewable and they must be considered as significant social and economic development drivers. In recent years, their contribution to a higher quality of life has been recognized at various levels. This is not the case with their financing. Financial solutions are still far from affordable and accessable. In this regard, the article examines the possibilities for financing the typical Bulgarian cultural institutions, namely the Chitalishte. First, the ways and methods of financing existing in the EU and in the world are presented.  After that, the real possibilities for them are evaluated in the Bulgarian context

Properties of obturations and obturation materials, associated with the development of secondary caries

The main part of dentists` work is associated with the operative treatment of dental caries, aiming at the sta­bilization of the process and restoration of the natural anatomy and function of the teeth with artificial ma­terials. With the emergence of restorative dental medicine came the questions related to the survival rate of the restorations, the reasons for their replacement and the possibilities for control and management of the factors, leading to activation and progression of the carious process.The aim of the literature overview is to study the most common reasons, leading to a decrease of the surviv­al rate of different restorations within the conditions of the mouth cavity. It analyzes factors with direct and indirect importance for the development of secondary caries and the longevity of obturations, such as po­lymerization shrinkage, accumulation of dental biofilm, micropermeability, marginal adaptation, micro­gap, etc

After pandemic cultural institutions’ management in the context of culture- development relation – the case of Bulgarian folklore ensemble

The paper discusses Bulgarian folklore dance ensemble as cultural institution in Covid-19 reality and its impact on development. Therefore, it considers the challenges imposed by the pandemic and the opportunities that  came along it. The analysis has showed that to have better and more significant impact, the ensemble must alleviate its internal weaknesses and explore new directions of creative work, different audiences, digitalization, wide partnerships, etc. Despite the increased awareness of the role of culture for local development, much can still be done to improve and mainstream across policy areas. Hence, the paper presents several clear policy measures to reinvest in culture and deliver a richer, more vibrant, and more diverse cultural sector, both at national and institutional level in order to boost its contribution to local development

A qualitative exploration of psychoanalytic psychotherapists' experiences working with young people who have perverse sexual fantasies and/or engage in harmful sexual behaviour

Objective: This study explores psychoanalytic psychotherapists’ (CPTs) experiences of working with young people (aged 14-25) who have perverse sexual fantasies, and/or engage in harmful sexual behaviour. Methods: Semi-structured interviews were conducted with five qualified CPTs working at the Portman Clinic. Interpretative Phenomenological Analysis (IPA) was employed to analyse the transcribed data. Results: IPA revealed 5 superordinate themes: 1. CPTs view perversion as an entrenched solution to emotional pain; 2. ''…it’s very, very disturbing to get hold of the aggressive, perverse part of the patient''; 3. In CPTs’ views, starting psychotherapy significantly increases the risk of harm to self and others, and it cannot be contained individually; 4. CPTs' gender matters; and 5. “an antidote to the disturbance” Conclusions: These findings have significant implications for clinical practice, emphasising the need to structure services with an awareness of the high risk involved, and the need for supervision and team support. They also highlight the benefits of long-term, open-ended treatment for these patients. Finally, it was revealed that having expertise in how to work with the aggressive part of these patient was another major necessity for all professionals working with these patients. Key words: Perversion, sexual offending behaviours, psychoanalysis, psychotherapy, counter-transference, adolescents

The Impact of Nursing Care in the Intensive Care Unit

As the population ages, the number of patients with more than one chronic disease increases, leading to a greater need for medical care. As a result, the demand for emergency and intensive care in recent years has become increasingly critical. It is advanced practice nurses who play a key role in patient care, and the drive to strengthen the workforce necessitates an increase in their involvement. The independence of advanced practice nurses and their impact on patient outcomes after critical care are of interest. The important role of nurses in the provision of health care has recently been recognized. Critical care needs inter-professional teams that provide collaborative health care, which includes the need for trained nurses. Expert and specialized care for the most seriously ill or injured patients in intensive care units (ICUs) and hospitals is provided by intensive care nurses. Working as part of a multidisciplinary team, they are experienced professionals who are highly skilled and safety-critical. The greatest responsibility for the care and treatment of patients in a critical or unstable clinical situation in the intensive care unit rests with the nurse. Her primary activities are the management and coordination of nursing care through assessments, therapies, and critical interventions. Based on the best available scientific evidence, clinical experience, and patient preferences, the nurse makes important clinical decisions in the intensive care unit

Sem analysis of the endodontic cavity wall after removal of restorative materials used as temporary restoration

Aim: The aim of the present in vitro study was to analyze the endodontic cavity walls for presence of remnants of conventional glass ionomer cement and flowable light cure composite used as temporary restorative materials of endodontically treated teeth. The dentine surface of the access cavity was observed with scanning electron microscopy after the final removal of the temporary restoration using high-speed turbine and diamond bur or ultrasonic device and diamond tip.Materials and methods: Twenty-one extracted intact human molars were selected for this study. Endodontic access, enlargement of the coronal one third of the root canals and standard irrigation were performed. Teeth were then restored with two different materials – conventional glass ionomer cement (Ketac Molar Easymix, 3M ESPE, USA) and flowable light cure composite (Vertise flow, KERR, USA) and divided in four groups according to the method of removal and type of material used for temporary restoration. One sample, positive for temporary material remnants, was used as a control group. After the removal of the restorative material, all specimens were prepared for SEM examination. Scanning Electron Microscopy (Prisma E SEM, Thermo Scientific, Eindhoven, The Netherlands) was used to examine the surface morphology of the samples. The samples were sputter-coated with gold using vacuum evaporator (JEOL JFC-1200). The images were recorded at 20 kV acceleration using various magnifications (×150, ×500, and ×1000).Results and conclusions: Remnants were detected in all specimens, regardless of the material for temporary restoration or method of removal

Histone acetyltransferase inhibitors: synthesis and in-vitro-testing

Die Enzymklasse der Histon-Acetyltransferasen (HATs) spielt in zellbiologischen Vorgängen und in der Ätiologie zahlreicher Erkrankungen eine fundamentale Rolle. Der Entwicklung von HAT-Inhibitoren als epigenetische Werkzeuge kommt eine wesentliche Bedeutung hinsichtlich neuer Erkenntnisse über zukünftige therapeutische Ansätze und die zugrunde liegenden Mechanismen zu. Im Rahmen der vorliegenden Arbeit wurden, ausgehend von Ergebnissen der Leitstruktursuche und -optimierung mittels computergestützter Methoden, zwei Substanzklassen als HAT-Hemmstoffe identifiziert. Anschließend wurden Strukturderivate synthetisiert und bezüglich ihrer HAT-Hemmung in vitro charakterisiert. Die abgeleiteten Struktur-Wirkungs-Beziehungen zeigten wiederum Ansatzpunkte für weitere Strukturoptimierung innerhalb der Enzymklasse auf. Hierzu wurde das in der Arbeitsgruppe für PCAF verfügbare antikörperbasierte heterogene Testsystem auf weitere Vertreter der HAT-Familie (Gcn5, CBP, p300) zwecks der Durchführung von Selektivitätsstudien übertragen. Darüber hinaus erfolgte erstmals in unserer Gruppe die Etablierung eines bakteriellen Überexpressionssystems zur heterologen PCAF-Gewinnung. Zum einen wurden Pyridoisothiazolone mit variierenden aromatischen Substituenten am Isothiazolon-Stickstoffatom als potente HAT-Hemmstoffe identifiziert. Diese Verbindungsklasse bildet nach Spaltung der S—N-Bindung kovalente Disulfid-Addukte mit Cysteinresten in Zielproteinen. Es konnte gezeigt werden, dass Substitutionsmuster am Isothiazolon-Stickstoffatom entscheidend für das Selektivitätsprofil der Inhibitoren ist. N-Phenyl-Derivate hemmten alle getesteten HATs im niedrigen mikromolaren Bereich, wohingegen N-Benzyl-Analoga selektive CBP-Hemmstoffe sind. Die Untersuchungen zur Aufklärung des zugrunde liegenden irreversiblen Hemmmechanismus belegen, dass die PCAF-Hemmung sehr schnell und vom Cofaktor unabhängig erfolgt und mit der Bildung stabiler Enzym-Inhibitor-Addukte einhergeht, welche sich durch nachträgliche Thioleinwirkung nicht spalten lassen. Die Ergebnisse der vorgenommenen Verdünnungsexperimente stützen zudem die Hypothese einer irreversiblen Hemmung. Die Reaktivität der S—N-Bindung im Isothiazolongrundgerüst wurde durch eine zweistufige Schwefeloxidation deutlich herabgesetzt, was in Inkubationsstudien mit Modellnukleophilen simuliert werden konnte und einen Verlust der HAT-Hemmung in vitro herbeiführte. Vergleichbare Effekte wurden für die Bindungsaffinität oxidierter Derivate an das Humane Serumalbumin (HSA) gefunden. In Kooperationsprojekten wurden für Vertreter dieser Substanzklasse wachstumshemmende Eigenschaften in mehreren Krebszelllinien aufgezeigt. Im Rahmen dieser Arbeit wurden weiterhin Rhodanin-Indolinon-Carbonsäuren als eine neue Klasse von HAT-Hemmstoffen charakterisiert, welche Vertreter der GNAT- und der p300/CBP-Familie ohne deutliche Selektivitätstendenzen hemmen. Die vorgenommenen chemischen Modifikationen ließen den Indolinonsubstituenten zum einen und den Rhodanin-Carbonsäure-Linker zum anderen als die Strukturbausteine mit einem entscheidenden Einfluss auf die Hemmeigenschaften und somit als Ansatzpunkte für eine weitere Optimierung erkennen. Im Einklang mit den Vorhersagen und Bindungsinteraktionen aus dem Molecular Modelling wurde zudem gezeigt, dass das Vorhandensein einer freien Carboxylfunktion essenziell für die In-vitro-Hemmung ist. The enzyme class of histone acetyltransferases (HATs) regulates fundamental cell-biological processes and is involved in the aetiology of several diseases. For this reason the development of small molecule inhibitors of histone acetyltransferase activities as epigenetic tools may provide insights into novel therapeutic approaches and contribute to the elucidation of the disease-related underlying mechanisms. Starting out from initial virtual screening und molecular modeling results, two different compound classes were identified as histone acetyltransferase inhibitors within this work. Subsequently, structural derivatives were synthesized and their HAT inhibitory properties were characterized in vitro. Structure-activity relationships were derived revealing starting points for further structural optimization in terms of selectivity. Concerning selectivity studies, a heterogeneous antibody-based assay system, developed for PCAF in our group, was transferred to other members of the HAT family (Gcn5, CBP, p300). In addition, a bacterial over expression system for heterologous PCAF production was established, which served as an accessible recombinant enzyme source for initial compound testing. Pyridoisothiazolones with varying aromatic substituents on the isothiazolone nitrogen atom were identified as potent HAT inhibitors. The mode of inhibition is linked to the cleavage of the sulphur-nitrogen bond in the main scaffold of the molecule with subsequent formation of covalent disulfide adducts with cysteine residues in target proteins. The substitution pattern on the isothiazolone nitrogen atom was shown to be crucial for the selectivity profile within the HAT family. N-phenyl derivatives were characterized as potent unselective low micromolar HAT inhibitors, whereas N-benzyl analogs were selective for CBP. Different approaches were performed in order to elucidate the proposed irreversible mode of action. The observed PCAF inhibition was attained very rapidly, independent of the cofactor amount and was associated with the formation of enzyme-inhibitor adducts stable against subsequent thiol treatment. Moreover, the performed dilution experiments also supported the hypothesis of an irreversible inhibition. The reactivity of the sulphur-nitrogen bond in the isothiazolone scaffold was significantly reduced by a two-step sulphur oxidation, which could be simulated in incubation studies with nucleophiles and resulted in a loss of HAT inhibition in vitro. Similar effects were found for the binding affinity of oxidized derivatives to the human serum albumin (HSA). Growth inhibitory properties for members of the pyridoisothiazolone compound class were demonstrated for a number of cancer cell lines in a cooperation project. A second class of moieties, whose main scaffold is a rhodanine-indolinone-carboxylic acid, was characterized as novel small molecule inhibitors of histone acetyltransferase activities, showing no selectivity trends within the GNAT and the p300/CBP families. The modifications introduced to the chemical structure led to the recognition of the indolinone substituent and the rhodanine carboxylic linker as structural units, providing the basis for further scaffold optimization. In line with molecular modelling predictions of the binding mode and interaction fields, the presence of a free carboxylic group was proved to be essential for in vitro inhibition. <br