The Potential of Liquid Biopsy in Detection of Endometrial Cancer Biomarkers: A Pilot Study.

Endometrial cancer belongs to the most common gynecologic cancer types globally, with increasing incidence. There are numerous ways of classifying different cases. The most recent decade has brought advances in molecular classification, which show more accurate prognostic factors and the possibility of personalised adjuvant treatment. In addition, diagnostic approaches lag behind these advances, with methods causing patients discomfort while lacking the reproducibility of tissue sampling for biopsy. Minimally invasive liquid biopsies could therefore represent an alternative screening and diagnostic approach in patients with endometrial cancer. The method could potentially detect molecular changes in this cancer type and identify patients at early stages. In this pilot study, we tested such a detection method based on circulating tumour DNA isolated from the peripheral blood plasma of 21 Slovak endometrial cancer patients. We successfully detected oncomutations in the circulating DNA of every single patient, although the prognostic value of the detected mutations failed to offer certainty. Furthermore, we detected changes associated with clonal hematopoiesis, including DNMT3A mutations, which were present in the majority of circulating tumour DNA samples.

Changes in DNA methylation associated with a specific mode of delivery: a pilot study.

Background: The mode of delivery represents an epigenetic factor with potential to affect further development of the individual by multiple mechanisms. DNA methylation may be one of them, representing a major epigenetic mechanism involving direct chemical modification of the individual's DNA. This pilot study aims to examine whether a specific mode of delivery induces changes of DNA methylation by comparing the umbilical cord blood and peripheral blood of the newborns. Methods: Blood samples from infants born by vaginal delivery and caesarean section were analysed to prepare the Methylseq library according to NEBNext enzymatic Methyl-seq Methylation Library Preparation Kit with further generation of target-enriched DNA libraries using the Twist Human Methylome Panel. DNA methylation status was determined using Illumina next-generation sequencing (NGS). Results: We identified 168 differentially methylated regions in umbilical cord blood samples and 157 regions in peripheral blood samples. These were associated with 59 common biological, metabolic and signalling pathways for umbilical cord and peripheral blood samples. Conclusion: Caesarean section is likely to represent an important epigenetic factor with the potential to induce changes in the genome that could play an important role in development of a broad spectrum of disorders. Our results could contribute to the elucidation of how epigenetic factors, such as a specific mode of delivery, could have adverse impact on health of an individual later in their life.

Mitochondrial DNA variability and Covid-19 in the Slovak population.

Recent studies have shown that mitochondria are involved in the pathogenesis of Covid-19. Mitochondria play a role in production of reactive oxygen species and induction of an innate immune response, both important during infections. Common variability of mitochondrial DNA (mtDNA) can affect oxidative phosphorylation and the risk or lethality of cardiovascular, neurodegenerative diseases and sepsis. However, it is unclear whether susceptibility of severe Covid-19 might be affected by mtDNA variation. Thus, we have analyzed mtDNA in a sample of 446 Slovak patients hospitalized due to Covid-19 and a control population group consisting of 1874 individuals. MtDNA variants in the HVRI region have been analyzed and classified into haplogroups at various phylogenetic levels. Binary logistic regression was used to assess the risk of Covid-19. Haplogroups T1, H11, K and variants 16256C > T, 16265A > C, 16293A > G, 16311 T > C and 16399A > G were associated with an increased Covid-19 risk. On contrary, Haplogroup J1, haplogroup clusters H + U5b and T2b + U5b, and the mtDNA variant 16189 T > C were associated with decreased risk of Covid-19. Following the application of the Bonferroni correction, statistical significance was observed exclusively for the cluster of haplogroups H + U5b. Unsurprisingly, the most significant factor contributing to the mortality of patients with Covid-19 is the age of patients. Our findings suggest that mtDNA haplogroups can play a role in Covid-19 pathogenesis, thus potentially useful in identifying susceptibility to its severe form. To confirm these associations, further studies taking into account the nuclear genome or other non-biological influences are needed.

COVID-19 and Diabetes Mellitus: Mutual Interplay of Two Diseases.

Currently, when the world is fighting against the rapidly spreading pandemic of COVID-19, the silent epidemic of diabetes should not be set aside. In comparison, while COVID- 19 led to about 6 million deaths in 2021, diabetes caused 6.7 million deaths in the same year. Diabetes mellitus is a serious risk factor for worse outcomes in COVID-19 patients. Moreover, it seems that there is a bidirectional relationship between pre-existing diabetes pandemic and the rapidly spreading COVID-19 pandemic. In this article, we summarize mechanisms by which SARS-CoV-2 infects the host cell and discuss the bidirectional relationship between diabetes and COVID-19. We also focus on clinical variables in which diabetic patients differ from non-diabetic patients and which could have promising predictive value for the course and outcome of diabetic COVID-19 patients' therapy management.

SARS-CoV-2 testing in the Slovak Republic from March 2020 to September 2022 - summary of the pandemic trends.

The COVID-19 pandemic has been part of Slovakia since March 2020. Intensive laboratory testing ended in October 2022, when the number of tests dropped significantly, but the state of the pandemic continues to this day. For the management of COVID-19, it is important to find an indicator that can predict pandemic changes in the community. The average daily/weekly Ct value with a certain time delay can predict changes in the number of cases of SARS-CoV-2 infection, which can be a useful indicator for the healthcare system. The study analyzed the results of 1,420,572 RT-qPCR tests provided by one accredited laboratory during the ongoing pandemic in Slovakia from March 2020 to September 2022. The total positivity of the analyzed tests was 24.64%. The average Ct values found were the highest in the age group of 3-5 years, equal to the number 30.75; the lowest were in the age group >65 years, equal to the number 27. The average weekly Ct values ranged from 22.33 (pandemic wave week) to 30.12 (summer week). We have summarized the results of SARS-CoV-2 diagnostic testing in Slovakia with the scope defined by the rate and positivity of tests carried out at Medirex a.s. laboratories.