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Major depressive disorder is one of the most severe mental disorders. It strongly impairs daily functioning, and, in extreme cases, it can lead to suicide. Although different treatment options are available for patients with depression, there is an ongoing search for novel therapeutic agents, such as scopolamine (also known as hyoscine), that would offer higher efficacy, a more rapid onset of action, and a more favorable safety profile. The aim of our study was to review the current clinical evidence regarding the use of scopolamine, a promising therapeutic option in the treatment of depression. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases up to 5 June 2023. We included randomized placebo-controlled or head-to-head clinical trials that compared the clinical efficacy and safety of scopolamine in the treatment of major depressive disorder. Two reviewers independently conducted the search and study selection and rated the risk of bias for each study. Four randomized controlled trials were identified in the systematic review. The included studies investigated the use of scopolamine administered as an oral, intramuscular, or intravenous drug, alone or in combination with other antidepressants. The results indicated that scopolamine exerts antidepressant effects of varying intensity. We show that not all studies confirmed a statistically and clinically significant reduction of depressive symptoms vs. placebo. A broader perspective on scopolamine use in antidepressant treatment should be confirmed in subsequent large randomized controlled trials assessing both effectiveness and safety. Therefore, studies directly comparing the effectiveness of scopolamine depending on the route of administration are required.

Considering the allosteric regulation of mGlu receptors for potential therapeutic applications, we developed a group of 1,2,4-oxadiazole derivatives that displayed mGlu4 receptor positive allosteric modulatory activity (EC50 = 282–656 nM). Selectivity screening revealed that they were devoid of activity at mGlu1, mGlu2 and mGlu5 receptors, but modulated mGlu7 and mGlu8 receptors, thus were classified as group III-preferring mGlu receptor agents. None of the compounds was active towards hERG channels or in the mini-AMES test. The most potent in vitro mGlu4 PAM derivative 52 (N-(3-chloro-4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)phenyl)picolinamide) was readily absorbed after i.p. administration (male Albino Swiss mice) and reached a maximum brain concentration of 949.76 ng/mL. Five modulators (34, 37, 52, 60 and 62) demonstrated significant anxiolytic- and antipsychotic-like properties in the SIH and DOI-induced head twitch test, respectively. Promising data were obtained, especially for N-(4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)picolinamide (62), whose effects in the DOI-induced head twitch test were comparable to those of clozapine and better than those reported for the selective mGlu4 PAM ADX88178.

This study explores whether and to what extent voters expect the government to provide jobs for everyone who wants to work. It examines the link between voter expectations and the labour market situation. It finds that the stronger the expectation of the government to provide a job for everyone in the mid-1990s was, the worse the labour market situation is today. Two hypotheses inspired by the theory of public choice are proposed to explain this relationship: (1) societal expectations were not correlated with reforms of labour market institutions in the next two decades; (2) support for the idea of the government providing a job for everyone was significantly lower among the employed (who in many countries constituted the majority of voters) than among other groups, and this difference did not depend on the labour market situation. The empirical analysis is based on a set of 29 indicators of labour market institutions and covers countries included in the Role of Government survey for 1996–2016 — conducted as part of the International Social Survey Programme. The obtained results are largely consistent with the stated hypotheses.

Abstract Background The problem of inappropriate use of antibiotics and the resulting growth in antimicrobial resistance (AMR) has implications for Poland and the world. The objective of this paper was to compare and contrast antibiotic resistance and antibiotic utilisation in Poland in recent years versus other European countries, including agreed quality indicators, alongside current AMR patterns and ongoing policies and initiatives in Poland to influence and improve antibiotic prescribing. Methods A quantitative ten-year analysis (2007–2016) of the use of antibiotics based on European Centre for Disease Prevention and Control (ECDC) data combined with a literature review on AMR rates and antimicrobial stewardship initiatives. Results The system of monitoring AMR and appropriate strategies to address AMR rates remain underdeveloped in Poland. The role of microbiological diagnostics and efforts to prevent infections is currently underestimated by physicians. Overall, Poland had one of the highest rates of total consumption of antibiotics in the analysed European countries. Total consumption of antibacterials for systemic use and relative consumption of beta-lactamase sensitive penicillins were characterized by small but statistically significant average annual increases between 2007 and 2016 (from 22.2 DIDs to 23.9 DIDs and from 0.8 to 1.3%, respectively). Conclusions The integrated activities around appropriate antibiotic prescribing in the pre- and post-graduate training of physicians and dentists seem to be particularly important, as well as changes in policies on prescribing antibiotics within ambulatory care. AMR and appropriate prescribing of antibiotics should be the focus of health policy actions in Poland.

In publications concerning unconventional schemes can be seen working draft of different designs of rotation turning tools and tools with linear cutting edge. Sporadically, this tools has appeared in the specialized publications. So far its operational characteristics, mainly its considerable influence on machined surface quality, exceptional durability and possibility to be used to turn hard machinable and other materials. Some of its priorities are verified in this paper.

Objective: To review the reimbursement recommendations issued by selected European health technology assessment agencies for orphan drugs and the reimbursement status of these drugs; to assess the relationship between the type of recommendation and reimbursement status.Methods: The list of orphan drugs to be included in the analysis was obtained from the European Medicines Agency and Orphanet. Seven European states were included in the analysis: Belgium, England, France, Germany, Poland, Scotland, and Spain. For all identified orphan drugs, relevant data on the reimbursement status and type of recommendation were collected for each country. The relationship between the type of recommendation and reimbursement status was evaluated separately for each considered country, using Cohen’s kappa coefficient for the measurement of agreement; sub-analyses for oncology and metabolic drugs were performed.Results: Most reimbursement recommendations for orphan drugs were positive (71%), while approximately 17% were negative and almost 13% were conditional. The highest percentage of positive reimbursement recommendations was observed in Spain (97%) and France (95%) and the highest percentage of negative reimbursement recommendations was revealed for Poland (49%). On average, 65% of the 163 analyzed orphan drugs were reimbursed from public funds. The highest number of reimbursed orphan drugs was observed in Germany (n = 148), while the lowest, in Poland (n = 41). Considering all analyzed drugs, the highest agreement between recommendations and reimbursement status was observed for Spain (value of 1), and the lowest, for Germany (κ = -0.03).Conclusions: On average, more than 60% of identified orphan drugs were reimbursed from public funds in the included countries, and the majority of reimbursement recommendations were found to be positive. The agreement between reimbursement recommendations and reimbursement status differed between the countries, but overall, it did not show any patterns, as it ranged from -0.03 to 1 (κ coefficient).