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Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of skin/mucosal swelling, and/or attacks of severe abdominal pain when it affects the gastrointestinal tract. The disease might be unexpectedly fatal when the upper airways are compromised. HAE clinical presentation, disease course and prognosis are associated with significant disease burden and severely impaired quality of life. Lanadelumab is a breakthrough therapy for the prevention of attacks in HAE type 1 and 2 patients. This revolutionary approach to administer a single subcutaneous injection (once every two to four weeks) and achieve complete disease control has dramatically improved patient care resulting in significant change in the life of affected families. Current data support the drug's tolerability in adult and adolescent patients without notable safety concerns in both clinical research and real-world settings. Rational use of prophylactic treatments of HAE searches for a socio-economic balance, taking into account the life-long course of the disease, the public health funds who pay the monetary price, and the patients who might need to receive the therapy for a period longer than investigated during the development program. In this review, we address the current evidence on lanadelumab's tolerability, highlighting aspects of the drug's rationale use in clinical practice. Further studies need to investigate whether this therapy might be appropriate in other forms of angioedema, such as idiopathic primary angioedema and HAE with normal C1 inhibitor. Future efforts must focus to improve modern drugs' accessibility in more countries. Although modern prophylactic options lessen the risk of fatal laryngeal attacks, patients must be equipped with reliable on-demand therapies and be trained how to use them as such a risk cannot be fully diminished with potentially life-threatening attacks occurring even in subjects with successful and stable long-term prophylaxis. Notwithstanding, further studies are needed to identify early responders from non-responders and develop therapies for the latter.

The aim of the article is to present a model of the activities of the city tour provider organizations, involving relations with customers (tourists). The activities involving customer interactions include relations before, during and after the city tours. The model has been implemented to analyze the city tours of Sofa, Bulgaria. The results revealed that tours in Sofia are characterized by a high degree of interactivity between personnel and customers, and customers themselves, involvement of partners and intensive use of technologies.

Hereditary angioedema is a rare disease that can often be disabling or even life threatening because of the unpredictable, self-limiting, and localized swelling episodes involving cutaneous, subcutaneous, and mucosal sites. The last decades revealed a spectrum of possibilities to control the disease through the development of effective therapies that changed the life of many patients and families worldwide. This review summarizes the current literature regarding the general management and therapeutic approach in patients with hereditary angioedema, both with and without C1 inhibitor deficiency. Medications already available in the market and new drugs in different research stages of development are addressed. Recent decades saw a huge leap in identifying mechanisms of angioedema and developing modern safe and effective medications to both treat acute angioedema manifestations and control disease activity via prophylactic therapy. Further improvement is still needed, together with improving global accessibility of diagnostic tools and effective medications. Whether novel drugs will demonstrate a sustained cost/effectiveness ratio will be answered in the years to come when we will witness whether a majority of the patients will benefit from these major advances.

Through the free, emancipated by the adult game during the classical childhood, skills for constructive personal behavior in a social environment, understood as context competencies, are built. At present, the current legal basis, by which the competencies (knowledge, skills, relationships) required at the end of each age period are written down / determined, consists of the Pre-School and School Education Act of 2015 (PSSEA) and the hereto belonging Ordinance (Standard) on Civil, Health, Environmental and Intercultural Education (OCHEIE). According to these documents, the personal realization of each child in the educational institution is considered as a consequence of the unity between the activities of education, training and socialization in the conditions of kindergarten and elementary school.The satisfaction of the children's needs for emotional co-experience and communication through gaming activity in the conditions of kindergarten and school is the duty of the educator. The right to play is justified in Art. 31 para. 1 of the UN Convention on the Rights of the Child and Bulgarian children and primary teachers are professionally competent in their commitments to provide gaming resources in educational institutions. The diagnosis of specific context competences, developed through the game, that are met in the Standard on Civil, Health, Environmental and Intercultural Education is an activity, that is important for the proper social and psycho-physical development of the child. This activity can be implemented in three dimensions (research approaches):- Recognizing context competences within such key competences through Observation method;- Naming or the discovery of context competences within such key competences through the Interview method;- Objectification and justification of context competences within such key competences through the Survey and Expert assessment methods.The Observation and Interview methods are carried out in close interaction with the children. The respondents Survey and Expert Assessment methods are the pedagogues. The aim of the pilot study is to establish the reliability of the three approaches and on this basis to construct a reliable research methodology related to the development of contextual competences through gaming activity in the kindergarten and elementary school.

Background Defective nasal barrier function is implicated in allergic rhinitis, which results in persistent inflammation and clinical symptoms, among which congestion plays a prominent role. In searching ways to improve the efficacy of nasally applied drugs in this condition, we tested the hypothesis that hydroxypropylmethylcellulose (HPMC), known as a mucoprotective agent, could enhance the efficacy of a decongestant (oxymetazoline nasal spray, 0.05%) by "sealing" it to the mucosa. Methods This double-blind placebo-controlled study was conducted with 40 patients (mean age, 35 years; 23 women) with persistent allergic rhinitis. The patients were randomized to receive 1 puff of oxymetazoline, followed by 1 puff of either HPMC or lactose powder (placebo) twice a day for 7 days and then only oxymetazoline rescue medication for another week. Peak inspiratory nasal flow (PNIF) was measured for 360 minutes after oxymetazoline and HPMC or placebo insufflation on days 1 and 8, and at a single point on day 15. Symptoms assessments involve visual analog scales and total nasal symptom scores. Results HPMC significantly enhanced oxymetazoline-increased PNIF at days 1 (p = 0.042) and 8 (p = 0.006). Baseline PNIF was greater in the HPMC group at day 15 (p = 0.014), indicative of further reduced nasal congestion. All nasal symptoms improved in both groups at day 8, but only the HPMC group showed further amelioration at day 15. Rescue medication was smaller in the HPMC group between days 8 and 15. Conclusion HPMC enhances decongestion through mucoadhesion but may also be augmenting the mucosal barrier in allergic rhinitis, which explains the carryover efficacy of oxymetazoline for a week after its discontinuation. Clinical trial registration clinicaltrials.gov identifier: NCT01986582.

This chapter presents two team-based Local Environmental Action Plans (LEAP) case studies in the Bulgarian cities of Kurdzhali and Stara Zagora. Similar models are successfully in place in urban centres in Poland, Slovakia, the Czech Republic and Bulgaria. The chapter argues the relevant for many of the other local LEAP initiatives in Central and Eastern Europe's (CEE) and elsewhere. It focuses on the LEAP team functions that help improve environmental management in urban centres in CEE and the civil society agenda that the team-based LEAP approach promotes. The end of the Cold War has brought to the world a novel redistribution of power among states, markets and civil society. Government is increasingly sharing power with business and citizen or non-governmental organisations. The Regional Environmental and Health Offices had professional interests and competencies to participate in drafting local environmental action plans.