Safety of Oral Paracetamol – Analysis of Data from a Spontaneous Reporting System in Poland

Purpose: To determine the safety of oral coated paracetamol tablets 500 mg and oral suspension 120 mg/5 mL produced by Hasco-Lek Poland.Methods: We analyzed sales volume and data obtained from the  monitoring of spontaneous reports on the adverse effects of paracetamol collected in the period between November 2000 and June 2012.Results: A total of 45,694 units of coated paracetamol tablets (500 mg) and 6,048,289 units of paracetamol oral suspension (120 mg/5 mL) were marketed during that period. There were 4 spontaneous reports of adverse effects.Conclusion: Oral paracetamol is a safe medication rarely causing adverse effects but it is possible that the existing spontaneous monitoring system for adverse effects in Poland is not sensitive enough to detect all adverse effects, and needs improvement.Keywords: Adverse reaction, NSAIDs, Pharmacovigillance,  Pharmoepidemiolog

A model of ideological struggle

A general model for opinion formation and competition, like in ideological struggles is formulated. The underlying set is a closed one, like a country but in which the population size is variable in time. Several ideologies compete to increase their number of adepts. Such followers can be either converted from one ideology to another or become followers of an ideology though being previously ideologically-free. A reverse process is also allowed. We consider two kinds of conversion: unitary conversion, e.g. by means of mass communication tools, or binary conversion, e.g. by means of interactions between people. It is found that the steady state,when it exists, depends on the number of ideologies. Moreover when the number of ideologies increases some tension arises between them. This tension can change in the course of time. We propose to measure the ideology tensions through an appropriately defined scale index.Comment: 10 pages, 3 figures, 46 references, working pape

ATRT–SHH comprises three molecular subgroups with characteristic clinical and histopathological features and prognostic significance

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT–TYR, ATRT–MYC and ATRT–SHH. ATRT–SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT–SHH might also have biological and clinical importance. Consensus clustering of DNA methylation profiles and confirmatory t-SNE analysis of 65 ATRT–SHH yielded three robust molecular subgroups, i.e., SHH-1A, SHH-1B and SHH-2. These subgroups differed by median age of onset (SHH-1A: 18 months, SHH-1B: 107 months, SHH-2: 13 months) and tumor location (SHH-1A: 88% supratentorial; SHH-1B: 85% supratentorial; SHH-2: 93% infratentorial, often extending to the pineal region). Subgroups showed comparable SMARCB1 mutational profiles, but pathogenic/likely pathogenic SMARCB1 germline variants were over-represented in SHH-2 (63%) as compared to SHH-1A (20%) and SHH-1B (0%). Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome. In conclusion, ATRT–SHH comprises three subgroups characterized by SHH and Notch pathway activation, but divergent molecular and clinical features. Our data suggest that molecular subgrouping of ATRT–SHH has prognostic relevance and might aid to stratify patients within future clinical trials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-022-02424-5

State of food industry in Lower Silesia and the recommended directions of its development

W latach 2002-2010 nastąpił spadek udziału produkcji żywności na Dolnym Śląsku w odniesieniu do wielkości krajowych, pogorszyły się wyniki ekonomiczne tego sektora przemysłu i odnotowano w nim niski poziom nakładów na działalność innowacyjną. W regionie dominują małe przedsiębiorstwa przetwórstwa rolno-spożywczego, które nie są w stanie samodzielnie prowadzić prac badawczo-rozwojowych. W takiej sytuacji szans rozwoju dolnośląskiego przemysłu spożywczego i poprawy jego konkurencyjności można upatrywać w ściślejszej integracji z regionalnymi uczelniami oraz instytucjami zajmującymi się transferem wiedzy i innowacyjnych technologii.In the years 2002-2010 there was a drop in the production of food in Lower Silesia in comparison to national production, furthermore the economic results of this sector of industry diminished. The expenditure dedicated to innovative activities showed low values. The region was dominated by small enterprises from the food and agricultural processing industry, which were incapable of conducting independent research and development activities. The above summarized situation shows that the food industry has potential development chances and a possibility to increase its competitiveness only through a closer integration with regional universities and institutions whose main area of interest is the transfer of knowledge and innovative technologies

Bioinformatics Study of Structural Patterns in Plant MicroRNA Precursors

According to the RNA world theory, RNAs which stored genetic information and catalyzed chemical reactions had their contribution in the formation of current living organisms. In recent years, researchers studied this molecule diversity, i.a. focusing on small non-coding regulatory RNAs. Among them, of particular interest is evolutionarily ancient, 19–24 nt molecule of microRNA (miRNA). It has been already recognized as a regulator of gene expression in eukaryotes. In plants, miRNA plays a key role in the response to stress conditions and it participates in the process of growth and development. MicroRNAs originate from primary transcripts (pri-miRNA) encoded in the nuclear genome. They are processed from single-stranded stem-loop RNA precursors containing hairpin structures. While the mechanism of mature miRNA production in animals is better understood, its biogenesis in plants remains less clear. Herein, we present the results of bioinformatics analysis aimed at discovering how plant microRNAs are recognized within their precursors (pre-miRNAs). The study has been focused on sequential and structural motif identification in the neighbourhood of microRNA