Leki przeciwnadciśnieniowe a skażenie rakotwórczymi nitrozoaminami

At the end of June 2018 small amounts of highly carcinogenic N–nitrosamine — N–nitrosodimethylamine (NDMA) contaminations were found in some of the angiotensin II receptor AT1 antagonists (sartans) used to treat arterial hypertension. By July 2019, four N–nitrosamine impurities had been identified in sartans: NDMA, N–nitrosodiethylamine, N‑nitrosodiisopropylamine and N-nitroso-N-methyl-4-aminobutyric acid. Seven manufacturers of three contaminated active substances (valsartan, losartan and irbesartan) from China, India and Mexico had also been identified. These compounds had infiltrated the active pharmaceutical ingredients probably as a consequence of ill-considered synthesis modifications. The number of people who have been prescribed contaminated valsartan alone is estimated at around 20 million worldwide. This paper discusses the role of sartans in medicine in the context of the physiological significance of the renin–angiotensin–aldosterone system as well as the role of tetrazole moiety in the mechanism of sartans receptor activity. The synthesis of tetrazole moiety and its modifications have been characterized as possible causes of the appearance of nitrosamine impurities in sartans. The toxicological properties of nitrosamines are also briefly outlined. The fact that nitrosamines had been entering medicines for at least five years without the knowledge of the authorities responsible for the safety of medicines has exposed a gross malfunctioning of the system intended to guarantee the safety of medicinal products. The valsartan scandal has forced changes to some drug regulations, in particular the requirements for analytical procedures.At the end of June 2018 small amounts of highly carcinogenic N–nitrosamine — N–nitrosodimethylamine (NDMA) contaminations were found in some of the angiotensin II receptor AT1 antagonists (sartans) used to treat arterial hypertension. By July 2019, four N–nitrosamine impurities had been identified in sartans: NDMA, N–nitrosodiethylamine, N‑nitrosodiisopropylamine and N-nitroso-N-methyl-4-aminobutyric acid. Seven manufacturers of three contaminated active substances (valsartan, losartan and irbesartan) from China, India and Mexico had also been identified. These compounds had infiltrated the active pharmaceutical ingredients probably as a consequence of ill-considered synthesis modifications. The number of people who have been prescribed contaminated valsartan alone is estimated at around 20 million worldwide. This paper discusses the role of sartans in medicine in the context of the physiological significance of the renin–angiotensin–aldosterone system as well as the role of tetrazole moiety in the mechanism of sartans receptor activity. The synthesis of tetrazole moiety and its modifications have been characterized as possible causes of the appearance of nitrosamine impurities in sartans. The toxicological properties of nitrosamines are also briefly outlined. The fact that nitrosamines had been entering medicines for at least five years without the knowledge of the authorities responsible for the safety of medicines has exposed a gross malfunctioning of the system intended to guarantee the safety of medicinal products. The valsartan scandal has forced changes to some drug regulations, in particular the requirements for analytical procedures

Acute Valproic Acid Intoxication: An Attempt at Estimating the Correlation Between Serum Level and Clinical Manifestations

We investigated the association between serum valproic acid (VPA) levels and clinical conditions in patients after acute intoxication with this drug. We performed a retrospective study of cases of VPA intoxications hospitalized in Toxicology Unit in Cracow in 2 years of observation. The study included 26 patients (age: 35.69 ± 12.93 years). In all patients, the VPA plasma level was higher than the therapeutic range, mean ± SD: 275.32 ± 135.97 μg/ml. About half of poisoned patients described in this report were treated with VPA prior to the poisoning. We noted four cases of mixed VPA intoxications with ethanol. Acute pulmonary failure was observed in two persons. The mean hospital stay for all patients was 4.69 days. This analysis demonstrates that increased serum VPA levels, in acute intoxication with this drug, were associated with the severity of poisoning — in PSS (P = 0.019) and in Matthews coma scale (P = 0.022), diastolic pressure (P = 0.022) and length of stay in hospital (P = 0.001). No correlation was detected between the serum VPA concentration and the heart rate and systolic blood pressure. In persons treated with VPA earlier, the course of poisoning was less severe, although these results were not statistically significant

Transformers as Strong Lens Detectors- From Simulation to Surveys

With the upcoming large-scale surveys like LSST, we expect to find approximately $10^5$ strong gravitational lenses among data of many orders of magnitude larger. In this scenario, the usage of non-automated techniques is too time-consuming and hence impractical for science. For this reason, machine learning techniques started becoming an alternative to previous methods. We propose a new machine learning architecture, based on the principle of self-attention, trained to find strong gravitational lenses on simulated data from the Bologna Lens Challenge. Self-attention-based models have clear advantages compared to simpler CNNs and highly competing performance in comparison to the current state-of-art CNN models. We apply the proposed model to the Kilo Degree Survey, identifying some new strong lens candidates, however, these have been identified among a plethora of false positives which made the application of this model not so advantageous. Therefore, throughout this paper, we investigate the pitfalls of this approach, and possible solutions, such as transfer learning, are proposed.Comment: 8 pages, 7 figure

The Framework Catalogue of Digital Competences

The Framework Catalogue of Digital Competences Justyna Jasiewicz, Mirosław Filiciak, Anna Mierzecka, Kamil Śliwowski, Andrzej Klimczuk, Małgorzata Kisilowska, Alek Tarkowski & Jacek Zadrożny Centrum Cyfrowe Projekt: Polska (2015

Fuzzy querying: issues and perspectives

summary:The term query is widely used in the database as well as information retrieval communities. Basically, a query against a collection of information items (to be called later, for brevity, an information source) provides a formal description of the items of interest to the user posing this query. A source of information is meant here very generally. It may take the form of an archive of multimedia or textual documents, a database, or a knowledge base. In the three previous examples the information items are documents, records (rows in relational data model) and facts, respectively. In order to manage and access an information source, an appropriate system is defined which makes it possible to store, represent and retrieve information items by means of a formal query language. Information systems that make it possible to manage information items previously mentioned are information retrieval systems, data base management systems and knowledge based systems, respectively. Query languages of these systems usually refer to some features of entities represented by the items stored in an information source, e. g., keywords (index terms) in textual documents (documents archive), attributes (database) or arguments of facts (knowledge base). Thus, basically, a query may be seen as a set of selection conditions that should be met by an information item (its features) to be qualified as relevant with respect to the query. On the other hand, the query processing itself may be seen as consisting mainly of matching a query against the items of the information source. This process may be essentially more complex, as, e. g., in the case of knowledge bases where we deal with a whole chain of matching within the reasoning process. Often, a user faces the problem of how to express her or his information requirements in a formal query language supported by a given information system interface. These formal languages usually require a crisp (precise, unambiguous) specification of a query, while, for human beings, a query is best expressed in terms of a natural language – a very powerful, but ambiguous and imprecise medium. Thus, adding some flexibility to traditional querying systems seems to be a critical issue for enhancing their effectiveness and efficiency. In this paper, we discuss some recent advances and basic issues related to flexible querying based on the application of fuzzy logic. We focus on two areas corresponding to the type of information source under consideration, namely: information retrieval in which we primarily deal with archives of textual documents and database querying. Both areas share the same interest in fuzzy (linguistic) queries and flexible matching against items of information. However, they have also their specific features, and these are pointed out in the next sections. The third area, that of very broadly meant knowledge bases querying is dealt with in the paper by Peter Vojtáš, in this special issue. Specifically, the concept of matching, essential for querying, may be identified to some extent with the unification. In the mentioned paper, the issues related to the fuzzy unification are discussed. The matching of fuzzy concepts, from a slightly different perspective, is also the subject of the paper by Andrejková, in this issue. Another contribution relevant for the flexible querying of knowledge bases is the paper by Ch. Marsala, in this issue. Moreover, beside its application to querying itself, the concept of flexibility is usually extended to the representation of information to be queried. This is particularly evident in the area of information retrieval in which concepts of fuzzy logic fit very well into advanced indexing schemes for text documents. In case of database management systems, fuzzy logic based ideas have led to the development of imprecise/vague data representation models. These issues are also dealt with in the following sections. This paper is structured in two sections dealing with information retrieval and database querying, respectively. The paper is meant to provide a synthetic description of the research area of the papers appearing in this special issue of the Kybernetika. This issue is comprised of extended versions of selected papers presented at the session on fuzzy querying at the FSTA’2000 Conference held in Liptovský Mikuláš (Slovak Republic) in the winter of 2000. We refer to the other papers in this issue indicating their relevance for the topics discussed here

Powikłania chirurgiczne przeszczepiania nerek

W artykule przedstawiono powikłania chirurgiczne przeszczepiania nerek i sposoby postępowania w przypadku ich wystąpienia. Omówiono powikłania ogólnochirurgiczne, naczyniowe i urologiczne

CARBON STOCKS IN LITTLE AND SILESIAN BESKIDS SOILS AGRICULTURAL USE

Organic carbon stocks (SOCs) were determined in 14 pedons of the Little and Silesian Beskids (7 from each one: arable land and grassland) and compared with the C-stocks occurring in the soils of Ciężkowickie and Silesian Foothills. They were similar to SOCs in the soils of the Silesian Foothills, but significantly higher than in the soils of the Ciężkowickie Foothills. The participation of SOCs 0–30 cm layer at the stocks of this element in the whole pedon was higher than in the soils of the foothills. Different types of land used (arable land, grassland) did not affect the quantity of SOCs in pedons and layers

Patients who buy acetylsalicylic acid in Polish pharmacies — population characteristics and description of medical problem

Wstęp. Celem badania była charakterystyka pacjentów nabywających w ogólnodostępnych aptekach preparaty kwasu acetylosalicylowego (ASA) rekomendowanego w dawkach kardiologicznych, a także jej powiązanie z próbą stratyfikacji grup ryzyka tych osób. Materiał i metody. Wykorzystano wystandaryzowane ankiety w formie elektronicznej skierowane do pacjentów zgłaszających się do aptek. Wywiad przeprowadzali farmaceuci lub technicy farmaceutyczni. Wyniki. Badanie objęło 532 pacjentów, którzy kupili preparat ASA dla siebie. Większość z nich nie przybyła wcześniej incydentów sercowo-naczyniowych, zaś decyzja o rozpoczęciu leczenia stanowiła wynik rekomendacji profesjonalisty medycznego. Odsetek osób, które kierowały się reklamą mediach, był znacznie mniejszy i kształtował się na poziomie około 20%. Wnioski. Sugeruje się, że w kontekście stosowania preparatów ASA w dawkach kardiologicznych największe znaczenie nadal mają wskazania objęte profilaktyką pierwotną. Obserwacja ta implikuje konieczność wykonywania dodatkowych badań diagnostycznych w tej grupie pacjentów, jak również wskazuje na rolę lekarzy i farmaceutów w procesie monito­rowania farmakoterapii.Introduction. The aim of our study was to characterize patients in Poland who buy in pharmacies over-the-counter formulations of acetylsalicylic acid (ASA) in doses recommended by cardiologists as well as to attempt a risk stratification of this population. Material and methods. We used standardized electronic questionnaires addressed to patients coming to pharmacies. Patients were interviewed by pharmacists or pharmacy technicians. Results. The survey included 532 patients who bought ASA drug for themselves. Most of them have not previously had any cardiovascular events, and the decision to start ASA was the result of a medical professional’s recommendation. The percentage of people who were motivated by mass media advertising was much smaller, at approximately 20%. Conclusions. It is suggested that the most important indications for use of ASA in cardiologic doses are those concerning primary prevention. This observation warrants performing further diagnostic work-up, and points out to the role of physicians and pharmacists in therapy monitoring

Socio-economic structure of the Katowice voivodship

Opracowanie dotyczy struktury społeczno-ekonomicznej województwa ka-towickiego. Za pomocą wybranych metod ilościowych (analiza składowych głównych, analiza elementarnego połączenia Mc Quitty'ego, analiza dyskryminacyjna) wydzielono podstawowe typy regionalne województwa oraz dokonano oceny zastosowanych technik pod kątem potrzeb badań regionalnych

Epidemiological Study of Acute Poisoning for Antiepileptic Drugs: A 2-Year Retrospective Study in Cracow, Poland

The aim of this study was designed to examine the rate of occurrence of antiepileptic drug overdose in 2002 and 2012 in Cracow, Poland, and analyze the demographics and clinical features of the patients Antiepileptic drugs (AEDs) intoxication. A retrospective study included all the patients admitted in to the Toxicology Units in Cracow for AED intoxications in 2002 and in 2012. Patients were identified of discharge diagnoses (ICD-10). AED intoxication were 5.40% of the total admissions. Mean age of the patients was 35.88 ± 12.54 years. The female-to-male ratio was 1:1.7. The most frequent AED was carbamazepine (n = 140), followed by valproate (n = 31). The most frequent motivation was intentional intoxication (n = 166, 94.86%). Ethanol was coingested by 51 patients (29.14%). Most of the patients ingested other drugs (32%). Antiepileptic drugs intoxication accounted for only of 7.13% of all cases admitted to the abovementioned toxicology units in 2002 and 2012 in Cracow. Our studies show that most of the AED poisoning cases in those years were caused by drugs belonging to the old generation antiepileptic drugs, including carbamazepine and valproic acid. The majority of the intoxication cases was related to suicidal poisoning and commonest identified reason of self-intoxication were issues with self including attention-seeking behavior