Enrichment of Zα domains at cytoplasmic stress granules is due to their innate ability to bind to nucleic acids.

Zα domains recognize the left-handed helical Z conformation of double-stranded nucleic acids. They are found in proteins involved in the nucleic acid sensory pathway of the vertebrate innate immune system and host evasion by viral pathogens. Previously, it has been demonstrated that ADAR1 (encoded by ADAR in humans) and DAI (also known as ZBP1) localize to cytoplasmic stress granules (SGs), and this localization is mediated by their Zα domains. To investigate the mechanism, we determined the interactions and localization pattern for the N-terminal region of human DAI (ZαßDAI), which harbours two Zα domains, and for a ZαßDAI mutant deficient in nucleic acid binding. Electrophoretic mobility shift assays demonstrated the ability of ZαßDAI to bind to hyperedited nucleic acids, which are enriched in SGs. Furthermore, using immunofluorescence and immunoprecipitation coupled with mass spectrometry, we identified several interacting partners of the ZαßDAI-RNA complex in vivo under conditions of arsenite-induced stress. These interactions are lost upon loss of nucleic acid-binding ability or upon RNase treatment. Thus, we posit that the mechanism for the translocation of Zα domain-containing proteins to SGs is mainly mediated by the nucleic acid-binding ability of their Zα domains. This article has an associated First Person interview with Bharath Srinivasan, joint first author of the paper.

System-wide analyses of the fission yeast poly(A)+ RNA interactome reveal insights into organization and function of RNA-protein complexes.

Large RNA-binding complexes play a central role in gene expression and orchestrate production, function, and turnover of mRNAs. The accuracy and dynamics of RNA-protein interactions within these molecular machines are essential for their function and are mediated by RNA-binding proteins (RBPs). Here, we show that fission yeast whole-cell poly(A)+ RNA-protein crosslinking data provide information on the organization of RNA-protein complexes. To evaluate the relative enrichment of cellular RBPs on poly(A)+ RNA, we combine poly(A)+ RNA interactome capture with a whole-cell extract normalization procedure. This approach yields estimates of in vivo RNA-binding activities that identify subunits within multiprotein complexes that directly contact RNA. As validation, we trace RNA interactions of different functional modules of the 3' end processing machinery and reveal additional contacts. Extending our analysis to different mutants of the RNA exosome complex, we explore how substrate channeling through the complex is affected by mutation. Our data highlight the central role of the RNA helicase Mtl1 in regulation of the complex and provide insights into how different components contribute to engagement of the complex with substrate RNA. In addition, we characterize RNA-binding activities of novel RBPs that have been recurrently detected in the RNA interactomes of multiple species. We find that many of these, including cyclophilins and thioredoxins, are substoichiometric RNA interactors in vivo. Because RBPomes show very good overall agreement between species, we propose that the RNA-binding characteristics we observe in fission yeast are likely to apply to related proteins in higher eukaryotes as well.

Thermodynamic analysis of Zα domain-nucleic acid interactions.

DNA/RNA molecules adopting the left-handed conformation (Z-form) have been attributed with immunogenic properties. However, their biological role and importance have been a topic of debate for many years. The discovery of Z-DNA/RNA binding domains (Zα domains) in varied proteins that are involved in the innate immune response, such as the interferon inducible form of the RNA editing enzyme ADAR1 (p150), Z-DNA binding protein 1 (ZBP1), the fish kinase PKZ and the poxvirus inhibitor of interferon response E3L, indicates important roles of Z-DNA/RNA in immunity and self/non-self-discrimination. Such Zα domain-containing proteins recognize left-handed Z-DNA/RNA in a conformation-specific manner. Recent studies have implicated these domains in virus recognition. Given these important emerging roles for the Zα domains, it is pivotal to understand the mechanism of recognition of the Z-DNA/Z-RNA by these domains. To this end, we assessed the binding thermodynamics of Zα domain from ORF112 and ADAR1 on T(CG)3 and T(CG)6 oligonucleotides which have high propensity to adopt the Z-conformation. Our study highlights important differences in the mode of oligonucleotide binding by the two Zα domains originating from different proteins. Site-directed mutagenesis was employed together with isothermal titration calorimetry to tease apart finer details of the binding thermodynamics. Our work advances the understanding on binding thermodynamics of Zα domains to their cognate nucleic acid substrates and paves the ground for future efforts to gain a complete appreciation of this process.

Pharmacovigilance practice among pediatric neurologists from Poland and Germany.

OBJECTIVES: To compare the pediatric neurologists' knowledge, practice, and barriers to the pharmacovigilance (PV) process in Poland and Germany. METHODS: The research tool was an online anonymous questionnaire on Google Forms e-mailed to pediatric neurologists from Poland and Germany. RESULTS: The questionnaires were handed out to 830 pediatric neurologists and 371 expressed their consent to participate in the study. Most of the neurologists were familiar with the definition of PV and adverse drug reactions (ADRs). Only 34.10% of pediatric neurologists from Poland, and 38.88% from Germany believe that many ADRs are preventable and almost most of them believe it is necessary to report ADRs from children with epilepsy. Unfortunately, in opposite to this knowledge, only 37.79% of respondents from Poland and 40.32% from Germany felt co-responsible for reporting ADRs. The main reason for the neurologists not to report ADRs was a conviction that reporting ADRs would be an additional burden generating extra work. CONCLUSION: There is no big difference between the practice of PV by pediatric neurologists in Poland and Germany. System-regulated PV stabilization in the country translates into the practice of maintaining PV. Monitoring the safety of pharmacotherapy and knowledge of risks associated with ADRs should be included in the curricula of academic neurologics courses.

Epilepsy is a chronic disorder characterized by episodic, gratuitous seizures. Most children with epilepsy (CWE) rely on antiepileptic drugs causing adverse drug reactions (ADRs). Many ADRs are preventable if physicians actively participate in pharmacovigilance (PV), which its pivotal role is to ensure the safety of pharmacotherapy by e.g. permanent control of ADRs. The study aimed to compare the pediatric neurologists' (PN) knowledge, practice, and barriers to the PV process in Poland and Germany. The research tool was an online anonymous questionnaire on Google Forms e-mailed to PN from Poland and Germany. Only 34.10% of PN from Poland and 38.88% from Germany believe that many ADRs are preventable and almost most of them believe it is necessary to report ADRs from CWE. Unfortunately, in opposite to this knowledge, only 37.79% of respondents from Poland and 40.32% from Germany felt co-responsible for reporting ADRs. The main reason for the neurologists not to report ADRs was a conviction that reporting ADRs would be an additional burden generating extra work. There is no big difference between the practice of PV by PN in Poland and Germany. System-regulated PV stabilization in the country translates into the practice of maintaining PV.

Impact of patient knowledge on hypertension treatment adherence and efficacy: A single-centre study in Poland.

Introduction: Recent studies show that treatment of arterial hypertension is unsuccessful. This is due to the patients' insufficient knowledge of about the therapeutic methods and the consequences of not treating arterial hypertension. Objectives: The aim of the study was to evaluate the patients' knowledge concerning therapeutic options, prophylaxis, and complications of arterial hypertension. The study also assessed the effect of such knowledge on hypertension treatment adherence and efficacy. Patients and Methods: The survey included 488 patients (250 female and 238 male), aged over 18 years, diagnosed with and treated in outpatient and inpatient settings at selected healthcare institutions in Poland. A custom-made questionnaire, based on references on this subject, was the key tool in the present study. Information about the course of the disease and evaluation of hypertension treatment efficacy was based on the patients' medical records. Results: The study found that 54.7% of the subjects had good knowledge about arterial hypertension, 40.0% had average knowledge, and 5.3% had poor knowledge. The extent of knowledge about the disease was significantly dependent on the level of education and the place of receiving medical care (p< 0.05). Good knowledge was significantly associated with controlled blood pressure, number of antihypertensive drugs used, frequency of hospitalization, as well as with medication adherence, and healthy lifestyle behaviours (p< 0.05). Conclusions: More than half of the patients presented good knowledge but a large group still had poor knowledge, especially patients with a low level of education and with hypertension treated at a general practitioner's clinic. The results of our study clearly show that knowledge about arterial hypertension affects medication adherence and healthy lifestyle behaviours and improves hypertension treatment efficacy.

A survey of pharmacists' knowledge, attitudes and barriers in pharmaceutical care concept in Poland.

BACKGROUND: The major goals of pharmaceutical care (PC) are to improve the patient's quality of life and ensure safety of pharmacotherapy. Inclusion of a pharmacist in the multidisciplinary team caring for the patient and integration of state-of-the-art pharmaceutical services with medical care and nursing are some of the most important challenges that the health care system in Poland is facing. OBJECTIVES: To evaluate the pharmacists attitudes towards practice in, and knowledge of PC in Poland and to identify the barriers in PC provision. METHODS: The study was designed as a multicenter study, conducted among Polish pharmacists. Random sampling technique was employed to select the study group. Face-to-face questionnaire method was used to interview the pharmacists, upon obtaining their prior verbal consent to participate in the study. The study was conducted between January 2017 and September 2019. RESULTS: Only 15% of the pharmacists have ever attended a training on PC. 72% believed PC provision was necessary to ensure pharmacotherapy safety. Only 63% of the pharmacists believed that preventing and solving health-related and drug therapy problems for patients were their responsibilities. The main reason for non-provision of PC by the pharmacists was the lack of time for such activities, lack of legal regulations, lack of organizational facilities. CONCLUSION: This study indicates that implementation of PC is expected in Poland. Educational programs in this respect are urgently needed. PC provision should be included in the curricula of academic pharmaceutical courses.

Histone deacetylation promotes transcriptional silencing at facultative heterochromatin.

It is important to accurately regulate the expression of genes involved in development and environmental response. In the fission yeast Schizosaccharomyces pombe, meiotic genes are tightly repressed during vegetative growth. Despite being embedded in heterochromatin these genes are transcribed and believed to be repressed primarily at the level of RNA. However, the mechanism of facultative heterochromatin formation and the interplay with transcription regulation is not understood. We show genome-wide that HDAC-dependent histone deacetylation is a major determinant in transcriptional silencing of facultative heterochromatin domains. Indeed, mutation of class I/II HDACs leads to increased transcription of meiotic genes and accumulation of their mRNAs. Mechanistic dissection of the pho1 gene where, in response to phosphate, transient facultative heterochromatin is established by overlapping lncRNA transcription shows that the Clr3 HDAC contributes to silencing independently of SHREC, but in an lncRNA-dependent manner. We propose that HDACs promote facultative heterochromatin by establishing alternative transcriptional silencing.

How current biologic therapies affect the risk of major adverse cardiovascular events in patients with plaque psoriasis? A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Concerns have been raised about an increased risk of major adverse cardiovascular events (MACEs) - stroke, myocardial infarction and sudden cardiac death - in patients with plaque psoriasis receiving biologic therapies. AIM: This review and meta-analysis of randomized controlled trials (RCTs) was to evaluate the risk difference of MACEs between experimental and comparator interventions. MATERIAL AND METHODS: We searched MEDLINE database for suitable trials. Prior to that we identified the search strategy and eligibility criteria. Each RCT was double-blind, placebo controlled and scored five points in Jadad scale. We calculated risk difference (RD) with use of the Mantel-Haenszel fixed-effect method with 95% confidence intervals (CIs) and calculated i2 statistic to assess heterogeneity. A total of 43 RCTs were included, involving 19,161 patients. Overall, the risk of MACEs in the included studies was 0.1% (n = 21). RESULTS: There were no statistically significant risk differences in patients treated with biologic therapy vs. placebo (RD = 0.0; Z = 1.09; 95% CI: 0.0-0.0; p = 0.28); tumour necrosis inhibitors vs. placebo (RD = 0.0; Z = 0.47; 95% CI: -0.0-0.0; p = 0.64); anti-IL-17A agents vs. placebo (RD = 0.0; Z = 1.25; 95% CI: -0.0-0.01; p = 0.21); anti-IL-23 agents vs. placebo (RD = 0; Z = 0.36; 95% CI: -0.0-0.01; p = 0.72); anti-IL-12/23 agents vs. placebo (RD = 0.0; Z = 0.73; 95% CI: -0.0-0.0; p = 0.46). CONCLUSIONS: Further trials are needed, including longer follow-up and patients with an increased cardiovascular risk, to assess the risk of MACEs.

Safety of medicines-Pharmacists' knowledge, practice, and attitudes toward pharmacovigilance and adverse drug reactions reporting process.

PURPOSE: Patients' safety is a public concern in healthcare systems across the world and should be ensured, among others, by pharmacovigilance based on spontaneous reports of adverse drug reactions (ADRs). Spontaneous ADRs reporting is an important component of the pharmacovigilance system. The role of pharmacists in spontaneous ADRs reporting is crucial in the pharmacovigilance system since it helps to monitor the patients' treatment in real-life conditions. The aim of the study was to evaluate the pharmacists' attitudes to and knowledge on spontaneous ADRs reporting in Poland and to identify the reasons for underreporting of ADRs. METHODS: The study was conducted between January 2016 and January 2018. A self-administered questionnaire was designed and distributed to pharmacists. The pharmacists were randomly selected from the official database kept by the chief pharmaceutical inspectorate in Poland. RESULTS: Only 16% (n = 84) of the respondents have ever attended a training on pharmacovigilance. Eighty-one percent (N = 422) of pharmacists believe that not all synthetic drugs available on the market were safe. Twenty-eight percent (n = 146) of the respondents were certain about safety of drugs of natural origin, and 16% (n = 84) were of an opinion that adverse reactions following administration of such drugs should not be reported at all. CONCLUSIONS: To conclude, there is an increasing awareness of the need to develop pharmacovigilance practices. The current (not fully adhered to in practice) model of pharmacovigilance and its associated tools have been developed for synthetic drugs, and applying these methods to monitor safety of herbal medicines presents unique challenges.

Costs of inpatient care of depression in 2014 in Polish (Poznan) and German (Kiel) hospital.

Objectives: Depression is highly prevalent worldwide and generates significant economic burden. Despite this, there is still insufficient information on hospitalisation costs related to depression. Therefore, this paper presents a comparison of costs of inpatient care of depression among patients hospitalised in 2014 in Kiel (Germany) and in Poznan (Poland).Methods: The retrospective study was conducted from October 2015 to May 2017 in Kiel and in Poznan and concerned all patients (n = 548 and eventually included n = 444; 334 in Kiel and 110 in Poznan) hospitalised in these centres.Results: The annual cost of inpatient care of patients hospitalised due to depression in 2014 was EUR [Formula: see text] = EUR 9397.21 (total EUR 313,8667.2) in Kiel and EUR [Formula: see text] = EUR 2962.90 (total EUR 325,919.38) in Poznan. In Kiel, the most frequently prescribed medicine was mirtazapine while in Poznan it was venlafaxine.Conclusions: The 3-fold difference in average costs of hospitalisation might result from differences in funding of mental health care which in Poland needs urgent amendment. Besides, mental health care was underfunded in Poznan. In general, treatment was comprehensive in both centres. Non-pharmacological treatment, however, was more comprehensive in Kiel.KEY POINTSThe cost of inpatient care of depression was very high both in Kiel and Poznan.Inpatient care of depression is long-lasting, but a reduction in the length of hospital stay seems to be possible.Hospital stay is the main part of costs of inpatient care of depression.Treatment of depression should be comprehensive, but differences e.g. in pharmacotherapy used are possible between hospitals and/or countries.

Structural Characterization of Human Coronavirus NL63 N Protein.

Coronaviruses are responsible for upper and lower respiratory tract infections in humans. It is estimated that 1 to 10% of the population suffers annually from cold-like symptoms related to infection with human coronavirus NL63 (HCoV-NL63), an alphacoronavirus. The nucleocapsid (N) protein, the major structural component of the capsid, facilitates RNA packing, links the capsid to the envelope, and is also involved in multiple other processes, including viral replication and evasion of the immune system. Although the role of N protein in viral replication is relatively well described, no structural data are currently available regarding the N proteins of alphacoronaviruses. Moreover, our understanding of the mechanisms of RNA binding and nucleocapsid formation remains incomplete. In this study, we solved the crystal structures of the N- and C-terminal domains (NTD, residues 10 to 140, and CTD, residues 221 to 340, respectively) of the N protein of HCoV-NL63, both at a 1.5-Å resolution. Based on our structure of NTD solved here, we proposed and experimentally evaluated a model of RNA binding. The structure of the CTD reveals the mode of N protein dimerization. Overall, this study expands our understanding of the initial steps of N protein-nucleic acid interaction and may facilitate future efforts to control the associated infections.IMPORTANCE Coronaviruses are responsible for the common cold and other respiratory tract infections in humans. According to multiple studies, 1 to 10% of the population is infected each year with HCoV-NL63. Viruses are relatively simple organisms composed of a few proteins and the nucleic acids that carry the information determining their composition. The nucleocapsid (N) protein studied in this work protects the nucleic acid from the environmental factors during virus transmission. This study investigated the structural arrangement of N protein, explaining the first steps of its interaction with nucleic acid at the initial stages of virus structure assembly. The results expand our understanding of coronavirus physiology and may facilitate future efforts to control the associated infections.

The Structure of the Cyprinid herpesvirus 3 ORF112-Zα·Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response.

In vertebrate species, the innate immune system down-regulates protein translation in response to viral infection through the action of the double-stranded RNA (dsRNA)-activated protein kinase (PKR). In some teleost species another protein kinase, Z-DNA-dependent protein kinase (PKZ), plays a similar role but instead of dsRNA binding domains, PKZ has Zα domains. These domains recognize the left-handed conformer of dsDNA and dsRNA known as Z-DNA/Z-RNA. Cyprinid herpesvirus 3 infects common and koi carp, which have PKZ, and encodes the ORF112 protein that itself bears a Zα domain, a putative competitive inhibitor of PKZ. Here we present the crystal structure of ORF112-Zα in complex with an 18-bp CpG DNA repeat, at 1.5 Å. We demonstrate that the bound DNA is in the left-handed conformation and identify key interactions for the specificity of ORF112. Localization of ORF112 protein in stress granules induced in Cyprinid herpesvirus 3-infected fish cells suggests a functional behavior similar to that of Zα domains of the interferon-regulated, nucleic acid surveillance proteins ADAR1 and DAI.

The Cost of Inpatient Care of Schizophrenia and Treatment Schedules Used in German Academic Center: Kiel.

The authors aimed at analyzing the costs of inpatient care of schizophrenia in Kiel (Germany). The study was also to present treatment regimens used at the German Academic Center. Moreover, the study is a continuation and complement of the previous study conducted in Polish and Ukrainian Academic Center. Therefore, it helps increase the awareness and knowledge of residents concerning the cost of inpatient care of schizophrenia. The analysis was based on 105 hospital records of patients treated between January 2012 and June 2013. According to inclusion criteria, 50 adult patients (27 women and 23 men) were included in the study. The study was approved by the Ethics Committee of the Medicine Faculty of CAU in Kiel. The cost of schizophrenia treatment of 50 patients in Kiel was EUR 604,280.90 ([Formula: see text] = EUR 12,085.62). The duration of hospital stay was on average [Formula: see text] = 51.02 days. The patients were treated with neuroleptics of all generations. The most popular atypical neuroleptic was amisulpride and the most popular typical neuroleptic was haloperidol. Patients from Kiel were provided a comprehensive non-pharmacological treatment. Treatment regiments and evaluations of costs of schizophrenia vary between countries. The costs of inpatient care of schizophrenia are high in Kiel. Treatment of schizophrenia seems to be comprehensive in Kiel and wide range of treatment opportunities contribute to a more effective treatment confirmed by less frequent relapses of schizophrenia than in Lviv (Ukraine), for example. Comprehensive treatment should be available everywhere, because it is a right of every patient.

Schizophrenia and Employment: Evaluation From Professionals Point of View.

Schizophrenia is a severe and chronic disorder requiring long-lasting and comprehensive treatment. Because of this disorder patients are socially isolated. Consequently, schizophrenia has a significant economic burden both in a group of direct and indirect costs. The aim was to analyse experts' opinions in the field of psychiatry concerning work possibilities among people with schizophrenia and to present the importance of employment for more effective treatment. A worldwide study was conducted between June 2011 and June 2013 using a questionnaire consisting of six open-closed questions and a short metrics. The questionnaire was delivered to experts and spread all over the world by post and via the internet. Over 3000 questionnaires were sent and the addressed specialists were requested to return them. From received 403 questionnaires 320 were included into the study, based on adopted inclusion and exclusion criteria. Although patients are afraid of looking for a job, respondents indicated that they crave for employment. The number of people that are able to work during remission of schizophrenia is considerably higher (50.35 %) than the number of actually employed (15.85 %). Non-pharmacological therapies were indicated as important to improve patients' chances of finding a job during remission of schizophrenia. The number of people that can work during remission of schizophrenia is considerably higher than the number of affected people employed. Patients crave for a job and supported employment should be treated as priority by health-care decision makers.

The cost of inpatient care of schizophrenia in the Polish and Ukrainian academic centers--Poznan and Lviv.

OBJECTIVE: The authors aimed to analyze and compare treatments of schizophrenia in Poznan and Lviv to present the potential differences between Poland and Ukraine in pharmacotherapy and economic availability of medicines, to emphasize the role of academic centers in the effective treatment of schizophrenia, and to raise the awareness of residents about economics and the cost of inpatient care. METHODS: The analysis was based on 307 hospital records of patients treated in 2010 and 2011 and data from the hospital accounting department. Per the inclusion criteria, 108 adult patients (50 in Poznan and 58 in Lviv) were enrolled in the study. Monetary values were converted into euros (EUR) at the rate published by the National Bank of Poland (NBP) on October 9, 2012. RESULTS: The total cost of schizophrenia treatment in Poznan was EUR 160,489.26, x = EUR 3,209.78 per patient, and in Lviv it was EUR 30,943.38, x = EUR 533.5 per patient. Treatment schedules differed between Poznan and Lviv, and pharmacotherapy was limited economically, especially in Lviv. CONCLUSION: Although the results differ between Poznan and Lviv, the study shows that schizophrenia treatment is expensive in both centers. Differences in the health care systems make use of innovative neuroleptics unavailable especially in Lviv, which may contribute to non-compliance or higher level of relapses. Distinctive efforts to improve therapies should be made and efforts to equalize access to innovative pharmacotherapy should be supported to improve the therapy's efficacy and the economic values of schizophrenia treatment.

Crystal structure of a poxvirus-like zalpha domain from cyprinid herpesvirus 3.

Zalpha domains are a subfamily of the winged helix-turn-helix domains sharing the unique ability to recognize CpG repeats in the left-handed Z-DNA conformation. In vertebrates, domains of this family are found exclusively in proteins that detect foreign nucleic acids and activate components of the antiviral interferon response. Moreover, poxviruses encode the Zalpha domain-containing protein E3L, a well-studied and potent inhibitor of interferon response. Here we describe a herpesvirus Zalpha-domain-containing protein (ORF112) from cyprinid herpesvirus 3. We demonstrate that ORF112 also binds CpG repeats in the left-handed conformation, and moreover, its structure at 1.75 Å reveals the Zalpha fold found in ADAR1, DAI, PKZ, and E3L. Unlike other Zalpha domains, however, ORF112 forms a dimer through a unique domain-swapping mechanism. Thus, ORF112 may be considered a new member of the Z-domain family having DNA binding properties similar to those of the poxvirus E3L inhibitor of interferon response.

Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats.

Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt's forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs.

Evaluation of antidepressant and memory-improving efficacy of aripiprazole and fluoxetine in alcohol-preferring rats.

INTRODUCTION AND AIMS: Dependence on ethanol increases the risk of depression in patients and leads to a damage and deficiencies of brain function, which manifest in cognitive functions impairment. Aripiprazole (ARI) is an atypical antipsychotic drug, which has also been shown to have a beneficial effect on cognitive function. Results of many studies show that, for ARI's antidepressant effect to manifest itself, it is necessary to use a combined therapy with a drug from the group of selective serotonin reuptake inhibitors (SSRIs). The aim of this paper was to assess the antidepressant and impact of ARI on spatial memory in alcohol-preferring rats (EtNPRs). DESIGN AND METHODS: In our study, we used Porsolt's forced swimming test (antidepressant effect) and Morris water maze test. The tests have been conducted upon administration of ARI (6 mg/kg i.p.), fluoxetine (FLX; 5 mg/kg p.o.) and combined administration of both drugs in alcohol-dependent rats. RESULTS: The results of behavioural tests carried out have shown a lack of antidepressant and procognitive effects of either ARI or FLX in EtPRs after acute and chronic treatment. Combined administration of both drugs would lead to spatial memory deterioration in the study animals. DISCUSSION AND CONCLUSIONS: Our results suggest that ARI applied in the experiment had no antidepressant effect and failed to improve spatial memory in study rats. Potential antidepressant and procognitive properties of this drug resulting from its mechanism of action encourage attempts (design) of further research aimed at developing a dose, which will show such effects in alcohol-preferring animals.

Analysis of Attitudes and Practices towards the Influenza Vaccine in High-Risk Adults in Poland.

This study aimed to understand Poles' attitudes and beliefs towards influenza vaccinations in the flu season of 2022-2023, especially among individuals at risk of flu complications. The cross-sectional survey-based study was carried out on a sample of 810 respondents. The questionnaire was disseminated electronically using social media and e-mail. The majority of respondents (71%) could identify "high-risk groups" recommended for influenza vaccination, and 52.01% of respondents reported receiving influenza vaccination at some point in the past, with 32.12% receiving it in the 2022-2023 flu season and 41.09% in the 2021-2022 season. The majority of respondents declaring acceptance of the vaccine for the 2022-2023 season were in the high-risk group. Only 17.28% of respondents declared receiving both influenza and SARS-CoV-2 vaccines in the 2022-2023 season, with the vast majority being respondents from the "high-risk group" (p < 0.0001). Only 26.12% of respondents declared their intention to continue influenza vaccination in the future. Of those expressing the intention to get vaccinated against the influenza virus in future seasons, 46.79% were from the "high-risk group" (p = 0.0087). Results suggest the need for further interaction and education with healthcare providers and targeted informational efforts for at-risk groups regarding the benefits of flu vaccination.

Medicines prices in International (Geary-Khamis) Dollar. The comparison between regulated and deregulated markets.

BACKGROUND: Affordability of medicines is key for effective healthcare. Thus, we compared medicine prices using International Dollar (I$), which allows confronting the values of different currencies. Besides, we intended to verify if pharmaceutical market deregulation leads to lower medicines prices. MATERIALS AND METHODS: We conducted the study between December 2019 and September 2022 collecting data from 21 countries. From the preliminary sampling of 30 medicines, we selected 10 brand names (5 Rx and 5 OTC brands) for the analysis. In each country, we collected price information from 3 pharmacies and then converted them to the I$ using the rates published by the International Monetary Fund. RESULTS: There were differences between regulated and deregulated markets in prices presented in I$. For instance, Aspirin C® (10 soluble pills) was on average I$ 5.41 in Finland (regulated market) and I$ 13.25 in Brazil. The most expensive Xarelto® 20 x 28 pills (I$ 538.40) was in Romania, which in the case of other medicines, was in the group of cheaper countries. There was no statistical significance in price comparison between regulated and deregulated markets. In some cases, however, regulated markets offered lower prices of the same medicine than deregulated markets. CONCLUSION: The analysis revealed differences in I$ prices between countries. Pharmaceutical market regulation does not mean higher prices of medicines. There is a need for affordable medicines. Hence, decision-makers should work on the medicines prices and adjust them to the local economies. I$ could be important in creating pharmaceuticals prices, and the conducted study should encourage other researchers to present their results using this currency.