Recent Labour Market Trends in the Visegrad Group Countries

The large declines in the Slovak and Czech employment appeared because the countries' GDPs grew smaller while real wages grew bigger. Shorter working hours and limitations on labour productivity that the two countries introduced could not reverse the unfavourable employment trends that occurred during economic downturn.Duże spadki zatrudnienia w Słowacji i Czechach były związane ze słabym wzrostem PKB i silnym wzrostem płac realnych. Redukcje czasu pracy i wydajności pracy nie były w stanie odwrócić niekorzystnych tendencji w zatrudnieniu

The Spread of ICT and Productivity Growth: Is Europe really lagging behind in the New Economy?

The economic performance of some OECD countries over the past decade, most notably the United States, has renewed the interest of analysts and policy makers on economic growth and on how policy can eventually support it. This report sheds some light on this issue by relying on harmonised macro and sectoral data for OECD countries and a unique cross-country firm-level dataset. This allows to address a number of issues. What are the key factors explaining differences in output and productivity performances across OECD countries? What is the role of ICT-producing industry and the ICT-driven capital deepening in explaining the different growth patterns of countries? Does the adoption of IC technologies require organisational changes and/or changes in the composition of inputs? What is the contribution of new firms to overall productivity growth in general and in ICT-related sectors? Do ICT-industries show stronger firm and employment turnover rates? Is there any relationship between the spread of ICT and institutional features of the product and labour markets? For example, do stringent regulations on start-ups (as well as those affecting incumbents) affect the diffusion of ICT? Do differences in labour market policy and institutions explain different patterns of adoption of new technologies?Macro data clearly point to widening disparities in growth performance across the OECD countries, even on the basis of cyclically-adjusted series. These disparities are related to differences in labour utilisation rather than to widening differences in labour productivity growth rates: i.e. higher growth rates in output per capita observed in a number of countries have been accompanied by improvements in the utilisation of labour, while sluggish employment in others (mainly in continental Europe) have not been fully compensated by higher labour productivity growth, thereby leading to a further slowdown in output growth. However, observed changes in growth patterns in some countries are also the result of the information and communication technology (ICT) revolution. In particular, it is argued that those countries that have developed an ICT-producing industry -- and/or where other industries have been quick in adopting highly productive ICT equipment -- have been able to shift to higher output and productivity growth paths. In this respect, the United States and some smaller countries (e.g. Australia, Ireland) have benefited the most from this ICT revolution, while most large European economies are still lagging behind. The sectoral and micro analysis also reveals important cross-country differences. The U.S. economy seems to be better able to acquire comparative advantage in rapidly growing ICT market segments than most of its trading partners. At the micro level, there seems to be a different degree of "market experimentation" in the United States compared with Europe, even if aggregate firm turnover rates are similar. The findings suggest that in the U.S. new firms tend to be smaller (relative to average incumbent) and less productive when compared with their European counterparts, but, if successful, they also tend to grow much more rapidly.The micro evidence reported in the paper offers additional elements in our discussion of a growth-enhancing policy setting. Our results seem to suggest that certain institutional and regulatory settings may reduce the degree of market experimentation of new firms. This, in turn, could lower the speed with which a country shifts to a new technology, thereby offering an interpretation to the observed differences in innovation and adoption across the Atlantic. For example, low administrative costs of start-ups and not unduly strict regulations on labour adjustments in the United States, may stimulate potential entrepreneurs to start on a small scale, test the market and, if successful with their business plan, expand rapidly to reach the minimum efficient scale. In contrast, higher entry and adjustment costs in Europe may stimulate a pre-market selection of business plans with less market experimentation. Our econometric results lend some support to these considerations. By using pooled data (country, industry and time) we find that stringent regulatory settings in the product and labour markets contribute to hinder innovation activity and the adoption of leading technologies

Glycosidase-catalyzed synthesis of glycosylated nutraceutical ingredients

Hydroxyphenyl propenoic acids (hydroxycinnamic acids) and their alcohol derivatives are common components of the human diet which often occur in plants in the form of various glycosides. As the diets rich in polyphenols have repeatedly been related to low incidence of cardiovascular, neurodegenerative, and oncological diseases, various food supplements containing these compounds are becoming increasingly popular among the general population. In quest of a biocatalytic route to structurally complex phenolic glycosides, we built a sustainable and convenient, one-pot two-enzyme method for the glucosylation of arylalkyl alcohols based on the synthetic exploitation of a fungal rutinosidase from A. niger and rhamnosidase from A. terreus. Both these enzymes were available to us as heterologous proteins produced by a recombinant strain of P. pastoris. As an example, the -glucoside salidroside, a compound endowed with various pharmacological effects and commercialized in Rhodiola rosea nutraceutical formulations, was obtained in high isolated yield and purity from tyrosol thanks to our one-pot enzymatic process. Furthermore, during the course of our investigation, we found that the rutinosidase from A. niger not only efficiently converted hydroxylated aromatic acids (e.g. coumaric and ferulic acids) into the respective phenolic rutinosides, but surprisingly could also catalyze the formation of the respective glycosyl esters. Here the results of our systematic study about the glycosidase-based biocatalytic preparation of lycosylated nutraceutical ingredients, which lead us to the discovery of a unique enzymatic entry to naturally occurring glycosyl esters, are reported

Dicarboxylic esters : useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

Dicarboxylic acids and their derivatives (esters and anhydrides) have been used as acylating agents in lipase-catalyzed reactions in organic solvents. The synthetic outcomes have been dimeric or hybrid derivatives of bioactive natural compounds as well as functionalized polyesters

OLIMPIC : a 12-month study on the criteria driving retreatment with ranibizumab in patients with visual impairment due to myopic choroidal neovascularization

Purpose: To evaluate criteria driving retreatment with ranibizumab in Italian patients with myopic choroidal neovascularization (mCNV). Methods: OLIMPIC was a 12-month, phase IIIb, open-label study. Patients with active mCNV were treated with ranibizumab 0.5 mg according to the European label. The study assessed local criteria in Italy driving retreatment decisions with ranibizumab; and the efficacy, safety, and tolerability of ranibizumab. Results: The mean (standard deviation [SD]) age of treated patients (N = 200) was 61.8 (12.7) years; range 22\u201385 years. The multivariate regression model indicated that presence of active leakage (odds ratio [OR] 95% confidence interval [CI]: 11.30 [1.03\u2013124.14]), presence of intraretinal fluid (OR [95%CI]: 28.21 [1.55\u2013513.73]), and an improvement in best-corrected visual acuity (BCVA) from baseline < 10 letters (OR [95%CI]: 17.60 [1.39\u2013222.75]) were the factors with the greatest effect on retreatment with ranibizumab. The mean (SD) BCVA gain from baseline to month 12 was 8.4 (12.8) letters (P < 0.0001). The mean (SD) number of injections was 2.41 (1.53); range 1\u20139. Ocular and non-ocular adverse events were reported in 41 (20.5%) and 30 (15.0%) patients, respectively. Conclusions: Individualized treatment with ranibizumab was effective in improving BCVA in patients with mCNV over 12 months. Both anatomical and functional variables had significant effects on causing retreatment. There were no new safety findings. Trial registration: www.ClinicalTrials.Gov (NCT No: NCT02034006)

New hydrophilic riminophenazines as potent antiprotozoal agents

Malaria and leishmaniasis are life-threatening human parasitosis caused by protozoa-infected insect vectors. In most of affected countries, the expansive and hazardous therapies available to fight protozoan infections are generally harmed by the spread of drug resistance phenomena upon prolonged treatments. This scenario highlights the need of novel antiprotozoal agents hopefully able to act trough new mechanism(s) of action. Interestingly, the fat-soluble antimycobacterial drug Clofazimine was reported to exhibit a moderate antiprotozoal action and some interesting antileishmanial in vitro and in vivo effects were reported in few preliminary, yet promising, studies.1,4 Intrigued by these results, we have previously prepared a series of basic Clofazimine analogues which demonstrated the beneficial effects of the introduction of a basic head on the antiprotozoal activity.5 Here, to further investigate the role of balancing between the lipo- and hydrophilicity on the antiparasitic activity of these riminophenazines, we report the synthesis and the in vitro evaluation as leishmanicidal (L. tropica and L. infantum promastigotes) and antiplasmodial (chloroquine sensitive and resistant P. falciparum strains) agents of a family of hydrophilic C-2 aminopyridinyl substituted riminophenazines, bearing in C-3 differently decorated basic side chains. Results showed that most of the new compounds potently inhibited the growth of protozoa with IC50 in the high nanomolar range and underlined the key role of the hydrophilic C-2 aminopyridinyl moiety to improve the leishmanicidal activity. In addition, the length and the nature of the basic side chain differently influenced the antiprotozoal activity and the selectivity index versus mammalian cells, providing useful information for further structural optimizations

Proteobacteria Overgrowth and Butyrate-Producing Taxa Depletion in the Gut Microbiota of Glycogen Storage Disease Type 1 Patients

A life-long dietary intervention can affect the substrates' availability for gut fermentation in metabolic diseases such as the glycogen-storage diseases (GSD). Besides drug consumption, the main treatment of types GSD-Ia and Ib to prevent metabolic complications is a specific diet with definite nutrient intakes. In order to evaluate how deeply this dietary treatment affects gut bacteria, we compared the gut microbiota of nine GSD-I subjects and 12 healthy controls (HC) through 16S rRNA gene sequencing; we assessed their dietary intake and nutrients, their microbial short chain fatty acids (SCFAs) via gas chromatography and their hematic values. Both alpha-diversity and phylogenetic analysis revealed a significant biodiversity reduction in the GSD group compared to the HC group, and highlighted profound differences of their gut microbiota. GSD subjects were characterized by an increase in the relative abundance of Enterobacteriaceae and Veillonellaceae families, while the beneficial genera Faecalibacterium and Oscillospira were significantly reduced. SCFA quantification revealed a significant increase of fecal acetate and propionate in GSD subjects, but with a beneficial role probably reduced due to unbalanced bacterial interactions; nutritional values correlated to bacterial genera were significantly different between experimental groups, with nearly opposite cohort trends

Target-Oriented Development Of Novel Antiprotozoal Agents: Celastrol Carboxamides As Inhibitors Of Leishmania Hsp90

The Leishmania isoform of the 90kDa Heat Shock Protein (LsHsp90), a chaperone known to assist the folding of more than 200 client proteins, was reported to be generally involved in parasite differentiation from promastigote to amastigote possessing a pivotal role during heat-induced cellular stress. Moreover, it was demonstrated that an impair of the native functions of LsHsp90 through the action of active-site inhibitors can exert a detrimental effect on the natural parasite life-cycle ultimately leading to its death. Celastrol is natural triterpene exhibiting a plethora of in vitro and in vivo activities. Among them, this pentacyclic compound is reported to possess a promising antiproliferative activity thanks to its ability of interacting with the chaperone cycle of the human isoform of Hsp90 (hHsp90). Moreover, celastrol derivatives (e.g. the methyl ester pristimerin, Figure 1) have also exhibited an interesting antiprotozoal activity. With the aim of building a target-oriented approach to treat Leishmania infections based on the inhibition of LsHsp90, we prepared two basic carboxamides celastrol derivatives (SS-1 and SS-2) to enhance its leishmanicidal activity and selectivity of action by deducting its unspecific cytotoxicity (measured as IC50 on HMEC-1 cell lines). Accordingly, celastrol and the two basic derivatives SS-1 and SS-2 were in vitro tested for their leishmanicidal activity against promastigotes of Leishmania tropica and L. infantum and, in parallel, their mechanism of action was investigated as well via ad hoc in vitro experiments using a recombinant Hsp90 from L. braziliensis (LbHsp90). In virtue of their pH sensitive basic heads, both SS-1 and SS-2 were found to be more potent (IC50 in the nanomolar range) and selective leishmanicidal agents than celastrol itself. Furthermore, we were able to demonstrate that SS-1 and SS-2 successfully (in vitro) inhibited the native kinase activity of LbHsp90 highlighting the key role of the inhibition of this chaperone in their mechanism of action

Enzymatic Synthesis of Valuable Bioactive Compounds

sustainable and convenient, one-pot two-enzyme method for the glucosylation of arylalkyl alcohols was developed (Scheme 1). The reaction scheme was based on a transrutinosylation catalyzed by a rutinosidase from A. niger using the cheap and commercially available flavonoid rutin as glycosyl donor, followed by a selective \u2018trimming\u2019 of the rutinoside unit, catalyzed by a rhamnosidase from A. terreus. Both these enzymes were available to us as heterologous proteins produced by a recombinant strain of P. pastoris. This process allowed the facile preparation of several natural bioactive glucosides, which could be isolated in up to 80% yield without the need of silica-gel chromatography