Medirex Group Academy

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and remains a major cause of mortality in intensive care units. Methods: We analyzed plasma levels of sTREM-1, CRP, PCT, sCD14-ST, HMGB1, IL-6, IL-10, vitamin D (VD), and sHLA-G in patients with SIRS/sepsis, and assessed their relationships with APACHE II, SOFA scores, and survival. Results: Septic patients showed significantly elevated sTREM-1, CRP, PCT, sCD14-ST, and higher neutrophil-to-lymphocyte ratio, while VD levels were markedly reduced. Logistic regression identified CRP and PCT as the strongest univariate predictors of sepsis, but after adjustment for age, sex, BMI, and comorbidities, CRP lost significance, whereas VD and sCD14-ST remained independent predictors. Prognostically, higher IL-10 levels significantly correlated with 7- and 28-day mortality and with SOFA scores, while higher VD concentrations predicted better survival. Conclusion: CRP, PCT, and sCD14-ST are reliable diagnostic biomarkers of sepsis, with sTREM-1 providing additional value for disease monitoring. After adjustment for clinical covariates, VD emerged as an independent protective factor, whereas elevated IL-10 significantly predicted 7- and 28-day mortality. These findings underscore the utility of combining inflammatory and immunoregulatory biomarkers to improve sepsis diagnostics and prognostication, warranting validation in larger multicenter cohorts.

Neonatal inflammatory skin and bowel disease 2 is an epidermal growth factor receptor (EGFR)-associated autosomal recessive early-infantile disease with inflammatory skin, alopecia, progeroid features, electrolyte imbalance, recurrent infections, and premature death. Pseudoxanthoma elasticum (PXE) is another autosomal recessive skin disorder with some ocular and cardiovascular alterations, caused by variations in the ATP binding cassette subfamily c member 6 (ABCC6) gene. However, ABCC6-deficiency is, rarely, also presented as as an early/late-infantile autosomal recessive generalized arterial calcification of infancy. In this case report we present the known homozygous EGFR p.G428D and the compound heterozygous ABCC6 p.R518* and p.R1221H variations in a 7-month-old Roma girl from a consanguineous family, who developed a combined EGFR/ABCC6-associated phenotype and died at 10 months of age. This case report and data in literature led us to conclude, that (1) EGFR-associated disease, with a serious early-infantile skin manifestation and occasional cardiovascular defects, may clinically overshadow other similar diseases such as generalized arterial calcification of infancy, if the single-gene/variant sequencing is used for diagnostics. (2) This probability increases if the person under investigation comes from a consanguineous family, and (3) the presented biallelic EGFR variation may be a co-factor of PXE severity. However, more analyses are required to make this conclusion definitive.

Urinary tract infections are one of the most common types of bacterial infections in childhood. Normally, empiric antibiotic therapy is given based on local antimicrobial susceptibility. We performed a retrospective study to evaluate bacterial resistance and clinical responses to antibiotics in childhood febrile urinary tract infections (fUTIs) in the Bratislava region of Slovakia. A total of 182 children with a fUTI were enrolled in our retrospective study. 84,07% of these fUTIs were caused by pathogenic Escherichia coli (E. coli). According to microbial antibiotic susceptibility tests, the most effective antibiotic agents were third-generation cephalosporins (susceptibility was observed in 92,16% (n=141) of the cases), followed by aminopenicillins with betalactamase inhibitor (susceptibility was observed in 84,97% (n=130) of the cases) and trimethoprim-sulfamethoxazole (susceptibility was observed in 79,74% (n=122) of the cases). In contrast, E. coli was susceptible to second-generation cephalosporins in just 3,92% (n=6). Patients treated with third-generation cephalosporins achieved a clinical response to therapy almost in all of the cases (95,7% (n=66)), whereas second-generation cephalosporins were associated with a clinical response to therapy in only 55,9% (n=33) of the cases. Third-generation cephalosporins and aminopenicillins with a betalactamase inhibitor appear to be the most suitable initial antibiotic therapies in pediatric patients with fUTIs. Following current guidelines alongside the regular assessment of regional microbial antibiotic susceptibilities should provide the best treatment management for children with fUTIs.

BackgroundOocytes of large animal species isolated from small ovarian follicles (< 2 mm) are less competent to support early embryonic development after in vitro maturation and fertilization than their counterparts isolated from medium-sized and preovulatory follicles. This study aimed to assess the effect of a new maturation medium containing FGF2, LIF, and IGF1 (FLI medium) on the meiotic and developmental competence of pig cumulus-oocytes complexes (COCs) derived from the small and medium-sized follicles.MethodsThe growing oocytes were isolated from 1 to 2 (small follicle; SF) and the fully-grown ones from 3 to 6 (large follicle; LF) mm follicles and matured in a control M199 medium with gonadotropins and EGF and the FLI medium enriched by the triplet of growth factors. The matured oocytes were parthenogenetically activated and cultured to the blastocyst stage. Chromatin configuration before and during the culture and MAP kinase activity were assessed in the oocytes. Finally, the expression of cumulus cell genes previously identified as markers of oocyte quality was assessed.ResultsThe maturation and blastocyst rates of oocytes gained from LF were significantly higher than that from SF in the control medium. In contrast, similar proportions of oocytes from LF and SF completed meiosis and developed to blastocysts when cultured in FLI. Most of the oocytes freshly isolated from SF possessed germinal vesicles with fine filaments of chromatin (GV0) or chromatin surrounding the nucleolus (GVI; 30%); the oocytes from LF were mainly in GVI (or GVII) exhibiting a few small lumps of chromatin beneath the nuclear membrane. When cultured in the FLI medium for 16 h, an acceleration of the course of maturation in oocytes both from SF and LF compared to the control medium was observed and a remarkable synchrony in the course of chromatin remodeling was noticed in oocytes from SF and LF.ConclusionsThis work demonstrates that the enrichment of culture medium by FGF2, LIF, and IGF1 can enhance the meiotic and developmental competence of not only fully-grown, but also growing pig oocytes and significantly thus expanding the number of oocytes available for various assisted reproductive technology applications.

During SARS-CoV-2 infection, the virus transforms the infected host cell into factories that produce new viral particles. As infection progresses, the infected cells undergo numerous changes in various pathways. One of these changes is the occurrence of a cytokine storm, which leads to severe symptoms. In this study, we examined the transcriptomic changes caused by COVID-19 by analyzing RNA-seq data obtained from COVID-19-positive patients as well as COVID-19-negative donors. RNA-seq data were collected for the purpose of identification of potential biomarkers associated with a different course of the disease. We analyzed the first datasets, consisting of 96 samples to validate our methods. The objective of this publication is to report the pilot results. To explore potential biomarkers related to disease severity, we conducted a differential expression analysis of human transcriptome, focusing on COVID-19 positivity and symptom severity. Given the large number of potential biomarkers we identified, we further performed pathway enrichment analysis with terms from Kyoto Encyclopedia of Genes and Genomics (KEGG) to obtain a more profound understanding of altered pathways. Our results indicate that pathways related to immune processes, response to infection, and multiple signaling pathways were affected. These findings align with several previous studies that also reported the influence of SARS-CoV-2 infection on these pathways.

Abstract BackgroundLynch Syndrome (LS) is an autosomal dominant hereditary syndrome associated with a diverse range of cancer types. Despite being one of the most prevalent hereditary cancer syndromes, the detection of LS remains challenging due to the absence of well-defined diagnostic criteria which would be able to select all patients who should undergo testing for LS and the limitations of existing screening methods. The implementation of an efficient screening program capable of accurately detecting the majority of LS cases remains a topic of continuous discussion in the scientific literature, with recent studies emphasizing the significance of a universal screening program.MethodsOur study aimed to develop and optimize a cost-effective universal screening method for detecting mutation in the mismatch repair (MMR) genes through mixed sample analysis. We tested five approaches in terms of the use of biological material and the analysis of mixed samples.ResultsEach approach successfully detected a specific Lynch-associated pathogenic variant in mixed in the pooled samples with frequency 5.00%, with the lowest allelic fraction recorded at 3.04%. Approach 2, which involved isolating DNA from each patient individually, demonstrated the highest average allelic fraction (7.04%). However, considering financial and time requirements, approach 1, where DNA was isolated only after mixing aliquots of whole blood, proved to be the most favorable.ConclusionThe findings of our study present a promising opportunity to improve LS detection. The identification of LS not only has the potential to prevent cancer-related morbidity and mortality but also facilitates continued progress in understanding the primary prevention of cancer.

Abstract 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 &gt; 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.

Medirex Group Academy biobank (MGA biobank) is a multidisciplinary disease-oriented project research biobank established in Nitra, Slovakia in October 2020. It evolves thanks to multiple research project and biomedical studies organized by non-profit organization Medirex Group Academy n.p.o. (Nitra, Slovakia). During 2020-2023, 27 clinics and 84 physician and nurses from 12 medical fields to participant enrolment, data and sample collecting and biobanking were involved. All together 4,346 participants were enrolled, 18,958 samples of different kind were collected and primarily processed for many downstream applications and for future use in research. Biobank is currently storing more than 53,000 biospecimen aliquots (whole blood, serum, plasma, stool, nasopharyngeal swab, native tissue, FFPE). For collecting patient data and information about samples was developed in-house MGA biobank information system (MGA BIMS). The aim of this study is to describe and evaluate current state and to define future prospective and development strategies. Since there is still no national biobank in Slovakia, it is important to further develop MGA biobank, to adapt standard processes so that in the future it meets all the requirements for implementation into European biobank structures and potentially became one of the important biobank nodes in Slovakia.

Cronobacter is a ubiquitous Gram-negative bacterium linked with serious infections. In this report, we describe the characterization of Cronobacter phage Dev_CS701, which was isolated from wastewater. Related to phages belonging to the Straboviridae family and Pseudotevenvirus genus, such as vB_CsaM_IeB, Dev_CS701 contains 257 predicted protein-coding genes and a tRNA gene.