Expression of selected angiogenesis-related small microRNAs in patients with abnormally increased secretion of glucocorticoids

Introduction: Higher cortisol levels are associated with cardiovascular morbidity and mortality in the elderly, partially resulting from biologic effects of glucocorticoids (GCs) on endothelial cells observed in an experimental setting. These features are replicated in patients with endogenous GC excess (Cushing’s syndrome) or with exogenous hypercortisolism due to excessive pharmacological application of GCs. Both groups present also an increased cardiovascular disease event rate. GCs may also adversely influence recovery after myocardial infarction. Recently it was proposed that microRNAs (miRNAs) — small noncoding RNAs functioning as antisense regulators of gene expression by targeting mRNA — may have a central role in regulating endothelial function through multiple mechanisms. Thus, the purpose of this study was to evaluate the effects of chronic GC excess on the expression of selected endothelium-controlling miRNAs expressed in nucleated cells circulating in peripheral blood (PBNCs) of patients with endogenous hypercortisolism either due to corticotrophin‐independent or corticotrophin‐dependent Cushing’s syndrome (CS). Material and methods: Peripheral blood nuclear cells were collected from 35 healthy subjects and 31 patients with endogenous hypercortisolism as a source of miRNAs. A self-validated individual quantitative RT-PCR study was then performed to evaluate the expression levels of selected miRNAs in PBNCs. Additionally, endothelin-1 (ET-1) expression in peripheral blood was assessed with respect to endothelial dysfunction using Western blotting. Results: The ET-1 expression levels in CS were higher than in controls, confirming endothelial dysfunction in the CS group. Furthermore, miRNA analysis revealed a significantly decreased intracellular expression of selected endothelium-related miRNAs in patients with endogenous hypercortisolism, including miRNA-17-5p, miRNA-126-3p, and miRNA-126-5p, compared to controls. In contrast, two other angiogenic miRNAs, miRNA-150-5p and miRNA-223-3p, were significantly upregulated compared to controls. Conclusions: Cardiovascular events related to hypercortisolism remain a challenging problem in medical practice. This study has demonstrated that the chronic excess of GCs in endogenous CS might induce significant dysregulation of selected miRNAs involved in the control of endothelium biology. However, the lack of knowledge about specific miRNA expression postpones the full understanding of the biological roles of such miRNAs in hypercortisolism. Moreover, dysregulated miRNAs seem to be promising targets for further research, especially to search for potential therapies for several GC-induced cardiovascular complications

Nauka prawa finansowego po I dekadzie XXI wieku

Księga pamiątkowa dedykowana profesorowi Apoloniuszowi Kosteckiem

In Search of the Innovative Digital Solutions Enhancing Social Pro-Environmental Engagement

Aim: In this paper, we analyze the potential of various digital tools such as gamification-based applications or digital currencies in enabling the social engagement in climate change mitigation processes by encouraging pro-environmental behaviors. Therefore, as a result of this study, we aim to develop a conceptual framework for a green digital tool, dedicated to cities seeking to shape their resilience by supporting bottom-up initiatives and encouraging residents to join the effort through educational interventions. Methods: The study was divided into four steps using a variety of methodological approaches, including a review of the SLR literature, analysis of the successes and failures of existing solutions, and qualitative workshops with stakeholders. Findings: The conceptual basis of the proposed solution has been developed based on the existing knowledge on pro-environmental nudging and lessons learnt from existing solutions. Value/originality: The developed conceptual framework can contribute to local economies while promoting social solidarity. It has the potential to build communities which can act together for the purpose of urban climate resilience because, from the very beginning, it is co-created together with residents. Practical implementation and beneficiaries: The concept described in this paper can serve cities as a supportive solution, shaping climate change awareness and attitudes toward active engagement

In Search of the Innovative Digital Solutions Enhancing Social Pro-Environmental Engagement

Aim: In this paper, we analyze the potential of various digital tools such as gamification-based applications or digital currencies in enabling the social engagement in climate change mitigation processes by encouraging pro-environmental behaviors. Therefore, as a result of this study, we aim to develop a conceptual framework for a green digital tool, dedicated to cities seeking to shape their resilience by supporting bottom-up initiatives and encouraging residents to join the effort through educational interventions. Methods: The study was divided into four steps using a variety of methodological approaches, including a review of the SLR literature, analysis of the successes and failures of existing solutions, and qualitative workshops with stakeholders. Findings: The conceptual basis of the proposed solution has been developed based on the existing knowledge on pro-environmental nudging and lessons learnt from existing solutions. Value/originality: The developed conceptual framework can contribute to local economies while promoting social solidarity. It has the potential to build communities which can act together for the purpose of urban climate resilience because, from the very beginning, it is co-created together with residents. Practical implementation and beneficiaries: The concept described in this paper can serve cities as a supportive solution, shaping climate change awareness and attitudes toward active engagement

Patient with Phenylketonuria and Intellectual Disability—Problem Not Always Caused Exclusively by Insufficient Metabolic Control (Coexistence of PKU and Alazami Syndrome)

The authors present a case report of a boy with a classical form of phenylketonuria and Alazami syndrome. The inborn error of phenylalanine metabolism was diagnosed in the neonatal period based on population new-born screening. Despite early implementation of a low-phenylalanine diet and good biochemical control, the patient developed behavioural disorders and intellectual disability. He also presented with dysmorphic features. After long and extensive attempts to establish the genetic cause of this unusual phenotype, finally, at the age of 16 the boy was diagnosed with Alazami syndrome based on whole exome sequencing. The authors discussed the problem of neuropsychological disorders in patients with phenylketonuria and described typical clinical symptoms of Alazami syndrome. It was emphasized that the presence of one monogenic disease does not exclude the coexistence of another one

Zasady leczenia żywieniowego na oddziałach intensywnej terapii dziecięcej. Wspólne stanowisko towarzystw naukowych: Sekcji Anestezji i Intensywnej Terapii Dziecięcej PTAiIT, PTN, PTŻKD

Providing nutritional therapy via the gastrointestinal tract in patients in paediatric intensive care units (PICUs) is an effective method for delivering energy and other nutrients. In the event of contraindications to using this method, it is necessary to commence parenteral nutrition. In the present study, methods for nutritional treatments in critically ill children are presented, depending on the clinical situation.Providing nutritional therapy via the gastrointestinal tract in patients in paediatric intensive care units (PICUs) is an effective method for delivering energy and other nutrients. In the event of contraindications to using this method, it is necessary to commence parenteral nutrition. In the present study, methods for nutritional treatments in critically ill children are presented, depending on the clinical situation

Newborn Screening for SCID and Other Severe Primary Immunodeficiency in the Polish-German Transborder Area: Experience From the First 14 Months of Collaboration

In 2017, in the Polish-German transborder area of West Pomerania, Mecklenburg-Western Pomerania, and Brandenburg, in collaboration with two centers in Warsaw, a partnership in the field of newborn screening (NBS) for severe primary immunodeficiency diseases (PID), mainly severe combined immunodeficiency (SCID), was initiated. SCID, but also some other severe PID, is a group of disorders characterized by the absence of T and/or B and NK cells. Affected infants are susceptible to life-threatening infections, but early detection gives a chance for effective treatment. The prevalence of SCID in the Polish and German populations is unknown but can be comparable to other countries (1:50,000–100,000). SCID NBS tests are based on real-time polymerase chain reaction (qPCR) and the measurement of a number of T cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and beta-actin (ACTB) as a quality marker of DNA. This method can also be effective in NBS for other severe PID with T- and/or B-cell lymphopenia, including combined immunodeficiency (CID) or agammaglobulinemia. During the 14 months of collaboration, 44,287 newborns were screened according to the ImmunoIVD protocol. Within 65 positive samples, seven were classified to immediate recall and 58 requested a second sample. Examination of the 58 second samples resulted in recalling one newborn. Confirmatory tests included immunophenotyping of lymphocyte subsets with extension to TCR repertoire, lymphoproliferation tests, radiosensitivity tests, maternal engraftment assays, and molecular tests. Final diagnosis included: one case of T-BlowNK+ SCID, one case of atypical Tlow BlowNK+ CID, one case of autosomal recessive agammaglobulinemia, and one case of Nijmegen breakage syndrome. Among four other positive results, three infants presented with T- and/or B-cell lymphopenia due to either the mother's immunosuppression, prematurity, or unknown reasons, which resolved or almost normalized in the first months of life. One newborn was classified as truly false positive. The overall positive predictive value (PPV) for the diagnosis of severe PID was 50.0%. This is the first population screening study that allowed identification of newborns with T and/or B immunodeficiency in Central and Eastern Europe