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The aim of our study was to analyze the effect of recreational swimming on lung function and bronchial hyperresponsiveness (BHR) in patients with mild persistent asthma. This study included 65 patients with mild persistent asthma, who were divided into two groups: experimental group A (n = 45) and control group B (n = 20). Patients from both groups were treated with low doses of inhaled corticosteroids (ICS) and short-acting β2 agonists salbutamol as needed. Our program for patients in group A was combined asthma education with swimming (twice a week on a 1-h basis for the following 6 months). At the end of the study, in Group A, we found a statistically significant increase of lung function parameters FEV1 (forced expiratory volume in 1 sec) (3.55 vs. 3.65) (p < 0.01), FVC (forced vital capacity) (4.27 vs. 4.37) (p < 0.05), PEF (peak expiratory flow) (7.08 vs. 7.46) (p < 0.01), and statistically significant decrease of BHR (PD20 0.58 vs. 2.01) (p < 0.001). In Group B, there was a statistically significant improvement of FEV1 3.29 vs. 3.33 (p < 0.05) and although FVC, FEV1/FVC, and PEF were improved, it was not significant. When Groups A and B were compared at the end of the study, there was a statistically significant difference of FVC (4.01 vs. 4.37), FEV1 (3.33 vs. 3.55), PEF (6.79 vs.7.46), and variability (p

International guidelines advocate the early introduction of inhaled corticosteroids (ICS) in all types of persistent asthma. Our study was undertaken to assess the effects of ICS on bronchial hyperresponsiveness (BHR) as a hallmark of inflammation, and to assess the symptoms, the use of rescue medications, and the parameters of lung function in patients with mild intermittent asthma. The patients with intermittent asthma (n = 85) were randomly allocated to a treatment with ICS, beclomethasone dipropionate 250 μg/day and short-acting β2 agonists salbutamol as needed (Group A, n = 45) or to a treatment with only short-acting β2 agonists as needed (Group B, n = 40) during the 6-month treatment period. At the end of the study, in Group A, we found a statistically significant decrease of BHR (PD20 0.98 vs. 2.07) (p < 0.001), diurnal peak expiratory flow (PEF) variability (17.9 vs. 13.8) (p < 0.001), symptom scores (0.63 vs. 0.30) (p < 0.001), and used rescue medication (p < 0.001), while the parameters of lung function remained unchanged except for forced expiratory volume in 1 sec (FEV1), which had a statistically significant increase (3.58 vs. 3.66) (p < 0.001). In Group B, there was a statistically significant decrease of lung function parameters FEV1 (3.80 vs. 3.71) (p < 0.001), forced vital capacity (FVC) (4.43 vs. 4.37) (p < 0.001), FEV1/FVC (88.2 vs. 85.3) (p < 0.05), PEF (8.05 vs. 7.51) (p < 0.01), PEF variability (17.85 vs. 18.33) (p < 0.001), increased BHR (PD20 1.04 vs. 0.62) (p < 0.05), and symptom scores (0.46 vs. 0.62) (p < 0.01), as well as the use of rescue medication during the day (p < 0.001). Early introduction of low doses of ICS may be more beneficial than β2 agonists alone in patients with intermittent asthma.

It is generally accepted that the National Innovation Systems (NIS) are one of the most comprehensive systemic approaches that give insight into innovative and economic performance of a country. This insight is essential for policymakers to develop legislatives for enhancing the innovative performance and success of today’s knowledge based economies. The development of the NIS is a complex, path-dependant process due to the differences in the development of the main sectors involved: the academia and the industry. Macedonian later emergence of the NIS is explained by the fact that after 1990, with the collapse of the Socialist Federal Republic of Yugoslavia (SFRY) there were significant losses in the Yugoslav, East and Central European markets. This process was accompanied by disintegration of many large industrial complexes, leading to a large number of bankruptcies and lay-offs. The existing strong governmental support for the scientific and research projects in the Federation was disrupted and disabled by these rapid changes, which was also reflected in the breakdown of direct links between academia and industry. The following two decades were transitional, and this period of recovery was terminated with the adoption of several strategic documents such as: industrial policy; program for science-research work and technological development; innovation strategy; and strategy for intellectual property. Finally, in 2013 the Law on Innovation Activity, which includes establishment of Innovation Fund, was adopted. This paper aims to retrospect the main activities for developing innovation infrastructure and enhancing innovation capacities. Moreover, it offers critical assessment of the improvements and the main challenges faced. The presented overview is designed to assist policymakers in further monitoring, evaluation and improvements, and to provide researchers with a solid base for the additional in-depth analysis of the impact of the implemented and proposed measures.

Plant biomass holds a promise for the production of second-generation ethanol via enzymatic hydrolysis, but its utilization as a biofuel resource is currently limited to a large extent by the cost and low efficiency of the cellulolytic enzymes. Considerable efforts have been dedicated to elucidate the mechanisms of the enzymatic process. It is well known that most cellulases possess a catalytic core domain and a carbohydrate binding module (CBM), without which the enzymatic activity can be drastically reduced. However, Cel12A members of the glycosyl hydrolases family 12 (GHF12) do not bear a CBM and yet are able to hydrolyze amorphous cellulose quite efficiently. Here, we use X-ray crystallography and molecular dynamics simulations to unravel the molecular basis underlying the catalytic capability of endoglucanase 3 from Trichoderma harzianum (ThEG3), a member of the GHF12 enzymes that lacks a CBM. A comparative analysis with the Cellulomonas fimi CBM identifies important residues mediating interactions of EG3s with amorphous regions of the cellulose. For instance, three aromatic residues constitute a harboring wall of hydrophobic contacts with the substrate in both ThEG3 and CfCBM structures. Moreover, residues at the entrance of the active site cleft of ThEG3 are identified, which might hydrogen bond to the substrate. We advocate that the ThEG3 residues Asn152 and Glu201 interact with the substrate similarly to the corresponding CfCBM residues Asn81 and Arg75. Altogether, these results show that CBM motifs are incorporated within the ThEG3 catalytic domain and suggest that the enzymatic efficiency is associated with the length and position of the substrate chain, being higher when the substrate interact with the aromatic residues at the entrance of the cleft and the catalytic triad. Our results provide guidelines for rational protein engineering aiming to improve interactions of GHF12 enzymes with cellulosic substrates.