BACKGROUND: Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. METHODS: A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. RESULTS: We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. CONCLUSIONS: In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.

• MeSH
• Diffuse Intrinsic Pontine Glioma genetics   diagnosis   blood   MeSH
• Child MeSH
• Epigenesis, Genetic MeSH
• Glioma genetics   diagnosis   blood   pathology   diagnostic imaging   MeSH
• Histones * genetics   metabolism   blood   MeSH
• Humans MeSH
• Adolescent MeSH
• Mutation MeSH
• Biomarkers, Tumor blood   MeSH
• Brain Stem Neoplasms genetics   diagnosis   blood   diagnostic imaging   pathology   metabolism   MeSH
• Child, Preschool MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: The etiopathogenesis of atopic dermatitis is complicated, and it includes aspects such as dysfunction of the skin barrier, changes in immune responses, IgE-mediated hypersensitivity, and many characteristics of the environment. Regarding skin barrier dysfunction, a number of genetic changes have been described. This genetic predisposition could be related to the phenotypes of atopic dermatitis. AIM: In this study, several polymorphisms in five proinflammatory genes were associated with certain phenotypes of AD patients (genotype-phenotype study). METHODS: In total, 89 unrelated AD Czech (Caucasian) patients were genotyped regarding five proinflammatory gene polymorphisms (angiotensinogen AGT M235T, AGT-6 G/A, TNF-α-238 G/A, TNF-β Fok1, IL-6-174 C/G and IL-6-596 G/A). Genotyping was performed using PCR and restriction analysis. For phenotypes, patients' sex, age and personal and family history of atopy, aero- and food allergies and other complex diseases were evaluated. RESULTS: A significant association with transepidermal water loss (TEWL) measured on the forearm was found with the AGT M235T polymorphism (p = 0.02). For the AG genotype of TNF-α-238 G/A, a six-times higher risk for a family history of diabetes mellitus compared to other examined aspects of family history was found (p = 0.02). A family history of thyreopathy was associated with the IL-6-174 G/C polymorphism when compared to a family history of other complex diseases. The GG genotype had a ten-times higher risk for a family history of thyreopathy compared to the other genotypes (p = 0.004). This result was highly specific (0.914). The GG genotype of IL-6-596 G/A was associated with a family history of thyreopathy, with the same result (p = 0.004). Moreover, the G allele of IL-6-174 G/C was associated with a family history of thyreopathy compared to AD patients without a positive family history of complex diseases (p = 0.03). In AD men, the MM genotype of the AGT M235T gene was found to be associated with food allergies (p = 0.004). This result was highly sensitive (0.833). A family history of cardiovascular disease in AD men was associated with AGT-6 G/A variability. The A allele was found to be six times more frequent in patients with a positive family history of cardiovascular disease (p = 0.02, with high sensitivity and specificity (0.700 and 0.735, respectively)). A family history of diabetes mellitus was associated with the TNF-β Fok1 polymorphism, where the B1 allele was almost six times more frequent in AD men with a positive family history of diabetes mellitus (p = 0.02), with high sensitivity (0.85). A significant association between TEWL measured on the forearm and the AGT M235T polymorphism was found when AD women were carriers of the MM genotype, with a median of 25 and range 4-61; those patients with the MT genotype had a median of 10 and range of 0.3-39; and patients with the TT genotype had a median of 5 and range of 3-40, p = 0.003. The polymorphism AGT-6 G/A was associated with different ages of eczema onset. The AG genotype was almost nine times more risky for the youngest group (0-7 years) compared to the oldest group (more than 18 years) (p = 0.02), with high specificity for this result. CONCLUSIONS: Our results in the field of cytokine signaling in the immune system in patients with atopic dermatitis are in agreement with those of GWASs. We suggest that cost-effective and simple PCR tests may be the best approach for the rapid and optimal collection of valid genetic information in clinical practice.

• MeSH
• Dermatitis, Atopic * genetics   pathology   MeSH
• Adult MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Genotype MeSH
• Interleukin-6 genetics   MeSH
• Polymorphism, Single Nucleotide MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Tumor Necrosis Factor-alpha genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Endometriosis, a complex inflammatory disease, affects a significant proportion of women of reproductive age, approximately 10-15%. The disease involves the growth of endometrial glands and stroma outside the uterine cavity, leading to tissue remodeling and fibrosis. Hormonal imbalances, accompanied by local and general inflammation and pain, are key features of endometriosis. Endometriotic lesions are associated with the overproduction of cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, and extracellular vesicles. Genetic predisposition and cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast cells, Th1 in the early phase, Th2 in the late phase, and T regulatory cells play a crucial role in endometriosis. Reduced NK cell function and impaired immune vigilance contribute to endometrial growth. The strong inflammatory condition of the endometrium poses a barrier to the proper implantation of the zygote, contributing to the infertility of these patients. Cytokines from various cell types vary with the severity of the disease. The role of microbiota in endometriosis is still under study. Endometriosis is associated with autoimmunity and ovarian cancer. Hormonal treatments and surgery are commonly used; however, recent interest focuses on anti-inflammatory and immunomodulatory therapies, including cytokine and anti-cytokine antibodies. Modulating the immune response has proven critical; however, more research is needed to optimize treatment for these patients.

• MeSH
• Cytokines metabolism   immunology   MeSH
• Endometriosis * immunology   therapy   pathology   etiology   MeSH
• Endometrium immunology   pathology   MeSH
• Humans MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Idiopatické střevní záněty, ulcerózní kolitida a Crohnova nemoc jsou celoživotní zánětlivá onemocnění s genetickým podkladem. Při kontaktu imunitního systému trávicí trubice s antigeny zevního prostředí a za spoluúčasti vlastní přirozené mikroflóry dochází ke ztrátě imunitní tolerance, selhání bariérové funkce střeva a k rozvoji poškozujícího zánětu s manifestací idiopatických střevních zánětů. Optimálních výsledků léčby dosahuje i přes pokroky ve vývoji biologické a cílené terapie cca třetina pacientů. Mirikizumab je první monoklonální protilátka proti p19 podjednotce IL-23, schválená pro léčbu UC v ČR. V naší kazuistice přinášíme zkušenosti s mirikizumabem v léčbě pacienta s refrakterní ulcerózní kolitidou.

Inflammatory bowel disease, ulcerative colitis and Crohn’s disease, are lifelong inflammatory diseases with a genetic basis. When the immune system of the digestive tract comes into contact with antigens from the external environment and the participation of its own natural microflora, there is a loss of immune tolerance, failure of the intestinal barrier function and the development of damaging inflammation with the manifestation of inflammatory bowel disease. Optimal treatment results, despite advances in the development of biological and targeted therapy, are achieved by approximately 1/3 of patients. Mirikizumab is the first monoclonal antibody against the p19 subunit of interleukin 23 approved for the treatment of ulcerative colitis in the Czech Republic. In our case study, we present our experience with mirikizumab in the treatment of a patient with refractory ulcerative colitis.

• Keywords
• mirikizumab,
• MeSH
• Child MeSH
• Antibodies, Monoclonal, Humanized pharmacology   therapeutic use   MeSH
• Humans MeSH
• Colitis, Ulcerative * drug therapy   physiopathology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

PURPOSE OF REVIEW: Recent advancements in the understanding of the genetic background of genitourinary cancers allowed for a successful introduction of targeted antitumor agents to prostate cancer (PCa) treatment. Inhibitors of the poly ADP-ribose polymerase enzyme (PARPi) transformed the treatment landscape of metastatic prostate cancer, and being increasingly studied in earlier disease stages. However, they are associated with nonnegligible toxicity, therefore, we aimed to summarize their side-effect profile in patients with PCa. RECENT FINDINGS: Hematologic toxicities, particularly anemia, thrombocytopenia, and neutropenia are among the most common and serious adverse events associated with PARPi, highlighting the need for regular blood count monitoring. Nonhematologic side effects, including fatigue, nausea, vomiting, diarrhea, and constipation, are common, and can be mitigated with supportive interventions like dietary modifications, antiemetics, or stool management techniques. Special attention should be given to patients with therapy-resistant or persistent cytopenia, in whom bone marrow biopsy should be considered, as it can indicate myelodysplastic syndrome and acute myeloid leukemia. SUMMARY: PARP inhibitors represent a major advancement in the management of metastatic prostate cancer, offering a significant survival benefit in applicable cases. However, patients need to be carefully selected and informed, to allow for optimal balancing between the benefits and nonneglectable risks of severe toxicities. Better understanding of PARPi toxicity profile can improve personalized decision-making and enhance treatment compliance, through raising patients' awareness about the possible side effects of PARPi.

• MeSH
• Humans MeSH
• Prostatic Neoplasms * drug therapy   pathology   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors * adverse effects   MeSH
• Urogenital Neoplasms * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Článek má za cíl seznámit čtenáře s problematikou farmakogenetického (PGx) vyšetření v oboru psychiatrie, které dnes představuje dostupný a významný nástroj personalizované medicíny. PGx testování umožňuje upravit farmakoterapii na základě genetických predispozic pacientů. V rámci oboru psychiatrie se zaměřuje zejména na polymorfismy v genech odpovědných za metabolismus léčiv, především enzymy cytochromu P450, jako jsou CYP2C19 a CYP2D6. Toto vyšetření může v praxi pomoci predikovat účinnost nebo toxicitu léčiv, a tím zlepšit bezpečnost a efektivitu farmakoterapie. Ve studii realizované v Psychiatrické nemocnici Bohnice byli testováni pacienti, kteří vykazovali známky farmakorezistence, odlišnost ve výsledcích vyšetření monitorování plazmatických hladin (TDM) nebo např. výrazné nežádoucí účinky při terapii běžnými dávkami. Až 75 % testovaných pacientů mělo změněnou funkci jednoho nebo obou testovaných izoenzymů CYP, tedy fenotyp pomalého, ultrarychlého, rychlého nebo intermediárního metabolizéra. Interpretace výsledků PGx vyšetření je klíčová a měla by být prováděna odborníkem, který má zkušenosti v této oblasti, hluboké znalosti farmakokinetiky a také veškeré potřebné informace o konkrétním pacientovi. Pouze v takovém případě může PGx vyšetření významně ovlivnit správný výběr a dávkování psychofarmak, jejichž účinnost závisí na fenotypu pacientů (zejm. risperidon, haloperidol, venlafaxin, tricyklická antidepresiva, es-/citalopram aj.). Správná interpretace výsledků také umožňuje optimalizaci medikace. To přispívá k minimalizaci rizika vzniku vedlejších účinků a zajištění lepších výstupů léčby. Na závěr je uvedena jedna kazuistika reflektující reálnou situaci, kdy PGx vyšetření sehrálo důležitou roli při rozhodování o výběru farmakoterapie.

Our article aims to introduce the reader to pharmacogenetic (PGx) testing in psychiatry, where it currently represents an available and significant tool in personalized medicine. PGx testing enables the adjustment of pharmacotherapy based on patients' genetic predispositions. In psychiatry, PGx testing focuses on polymorphisms in genes responsible for drug metabolism, primarily cytochrome P450 enzymes such as CYP2C19 and CYP2D6. In clinical practice, these tests can help predict drug efficacy or toxicity, thereby improving the safety and effectiveness of pharmacotherapy. PGx testing, which was conducted at the Bohnice Psychiatric Hospital, was done on patients who exhibited signs of drug resistance, discrepancies in therapeutic drug monitoring (TDM), or significant adverse effects during therapy with standard doses. Results showed that up to 75% of the tested patients had altered function of one or both CYP isoenzymes (i. e., slow, ultra-rapid, rapid, or intermediate metabolizer phenotypes). The interpretation of PGx test results is crucial and should be performed by professionals with expertise in this field. Additionally, a thorough understanding of pharmacokinetics, as well as comprehensive patient-specific information, is required. Only under these conditions can PGx testing significantly influence the correct selection and optimal dosing of psychotropic drugs, especially those whose effectiveness depends on the patient's phenotype (e.g., risperidone, haloperidol, venlafaxine, tricyclic antidepressants, es-/citalopram, etc.). Correct interpretation of PGx results also enables medication optimization, contributing to individualized therapy. This minimizes the risk of side effects and ensures better treatment outcomes. Our article concludes with a case report illustrating a real-life situation in which PGx testing played a key role in guiding pharmacotherapy decisions.

• MeSH
• Cytochrome P-450 CYP2D6 genetics   metabolism   MeSH
• Cytochrome P-450 CYP2C19 genetics   metabolism   MeSH
• Pharmacogenetics * MeSH
• Middle Aged MeSH
• Humans MeSH
• Schizophrenia, Paranoid drug therapy   pathology   MeSH
• Pilot Projects MeSH
• Polymorphism, Genetic MeSH
• Amphetamine-Related Disorders drug therapy   MeSH
• Psychotropic Drugs * administration & dosage   metabolism   therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

BACKGROUND AND OBJECTIVES: HLA-B27 is a genetic marker associated with spondyloarthropathies, particularly ankylosing spondylitis and axial spondyloarthritis. While its prevalence varies across populations, no data exist for Slovak patients. This study aimed to determine HLA-B27 prevalence in Slovak patients with suspected spondyloarthropathies and assess differences by sex and age. METHODS: A retrospective cohort of 1,614 patients (888 females and 726 males) was analyzed for HLA-B27 status (positive/negative) using reverse hybridisation (HLA-B27 StripAssay). Statistical analyses included Pearson's Chi-square test and non-parametric Mann-Whitney U and Kruskal-Wallis tests for sex- and age-related differences. RESULTS: HLA-B27 positivity was 20.57%, with a higher proportion in males (23.28%) than females (18.36%, p = 0.0177). The less than 20 age group had the highest absolute number of positive cases (126 cases; 17.80%), while the 21-40 group had the highest relative positivity (119 cases; 29.38%). The lowest positivity was in the more than 61 age group (17 cases; 13.08%), though age distribution differences were not statistically significant (p = 0.7765). Positivity varies across diagnoses, peaking in musculoskeletal (M) and eye disorders (H), where it exceeds 29%. CONCLUSION: HLA-B27 positivity is strongly associated with rheumatologic and ophthalmologic conditions and exhibits age- and sex-related variability. These findings emphasize the diagnostic significance of HLA-B27 testing in Slovak patients, especially for early detection and management of spondyloarthropathies. Further research on HLA-B27 variability and its clinical implications is needed to optimize diagnostic strategies and patient care.

• MeSH
• Child MeSH
• Adult MeSH
• HLA-B27 Antigen * genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Spondylarthropathies genetics   epidemiology   immunology   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Slovakia MeSH

Early detection of type 1 diabetes, in its presymptomatic stage, offers significant clinical advantages, including treatment that can delay disease onset. Current screening focuses on identifying islet autoantibody positivity, with proposed optimal testing at ages 2, 6 and 10 years potentially achieving up to 80% sensitivity. However, challenges arise from participation rates and costs associated with multiple screenings. Genetic pre-screening has been suggested as a complementary strategy to target high-risk individuals prior to autoantibody testing, but its real-world benefits remain uncertain. Broad genetic selection strategies, based on family history, HLA typing or polygenic risk scores, can identify subsets of the population at elevated risk. However, these approaches face issues like low recall rates, socioeconomic biases and limited applicability across diverse ancestries. Additionally, the cost-effectiveness and infrastructure requirements of integrating genetic testing into routine healthcare remain significant hurdles. The combined use of genetic and autoantibody testing could improve predictive value, especially with innovations like point-of-care genetic testing. Yet, the ultimate success of any screening programme depends less on specific strategies and more on maximising public and healthcare-provider engagement, ensuring high participation, and addressing socioeconomic and demographic disparities. Digital-health infrastructure may play a crucial role in improving recall rates and maintaining follow-up adherence. In conclusion, while repeated islet autoantibody screening remains the most effective standalone approach, conducting genetic screening prior to islet autoantibody testing may be practical in certain contexts, provided that sufficient resources and equitable strategies are employed. Public engagement and robust infrastructure are essential to realising the full potential of early type 1 diabetes detection programmes.

• MeSH
• Autoantibodies * immunology   MeSH
• Diabetes Mellitus, Type 1 * diagnosis   genetics   immunology   MeSH
• Genetic Testing * methods   MeSH
• Islets of Langerhans * immunology   MeSH
• Humans MeSH
• Mass Screening methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Despite extensive research on physical activity behaviour (PAB), consensus is lacking on related terms and definitions, thereby hindering the ability to compare findings between studies and to develop reliable assessment tools. This study therefore aimed to establish consensus on the definitions of key PAB determinants. METHODS: First, an international expert steering committee was established, comprising members of the European Cooperation in Science and Technology (COST) action "DEterminants of Physical ActivitieS in Settings" (DE-PASS). Recently published review-level studies were used to identify key determinants of PAB. Two independent reviewers systematically reviewed the literature to catalogue the range of definitions used for key determinants of PAB (steps 1-2). A two-round modified Delphi survey was conducted online from February to September 2023, to determine the optimal definition for each determinant. In round 1, experts selected the most suitable definition for each of the 41 initially identified determinants. In round 2, experts ranked the appropriateness of the definition selected from round 1 on a 5-point Likert scale. Consensus was defined a priori as ≥ 75% agreement on the definition (i.e., ratings of ≥ 4 points). A professional English language expert ensured concise, coherent wording and high-quality editing of the definitions (steps 3-6). RESULTS: Eighty-five experts in PAB research participated in round 1, and sixty-nine experts in round 2. Consensus of definitions was achieved for 39 of the 41 determinants (88.4%-98.6% agreement). The consensus threshold was not achieved for two determinants: genetic profile and regulation (69.6%) and backyard access/size (73.9%). CONCLUSIONS: The findings of this study offer a consensus-based set of definitions for 39 key determinants of PAB. These definitions can be used homogenously in academic research on physical activity.

• MeSH
• Exercise * MeSH
• Delphi Technique * MeSH
• Consensus * MeSH
• Humans MeSH
• Health Behavior MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Advancements in artificial intelligence (AI) and machine learning (ML) have revolutionized the medical field and transformed translational medicine. These technologies enable more accurate disease trajectory models while enhancing patient-centered care. However, challenges such as heterogeneous datasets, class imbalance, and scalability remain barriers to achieving optimal predictive performance. METHODS: This study proposes a novel AI-based framework that integrates Gradient Boosting Machines (GBM) and Deep Neural Networks (DNN) to address these challenges. The framework was evaluated using two distinct datasets: MIMIC-IV, a critical care database containing clinical data of critically ill patients, and the UK Biobank, which comprises genetic, clinical, and lifestyle data from 500,000 participants. Key performance metrics, including Accuracy, Precision, Recall, F1-Score, and AUROC, were used to assess the framework against traditional and advanced ML models. RESULTS: The proposed framework demonstrated superior performance compared to classical models such as Logistic Regression, Random Forest, Support Vector Machines (SVM), and Neural Networks. For example, on the UK Biobank dataset, the model achieved an AUROC of 0.96, significantly outperforming Neural Networks (0.92). The framework was also efficient, requiring only 32.4 s for training on MIMIC-IV, with low prediction latency, making it suitable for real-time applications. CONCLUSIONS: The proposed AI-based framework effectively addresses critical challenges in translational medicine, offering superior predictive accuracy and efficiency. Its robust performance across diverse datasets highlights its potential for integration into real-time clinical decision support systems, facilitating personalized medicine and improving patient outcomes. Future research will focus on enhancing scalability and interpretability for broader clinical applications.

• MeSH
• Databases, Factual MeSH
• Humans MeSH
• Neural Networks, Computer MeSH
• Patient-Centered Care * MeSH
• Machine Learning * MeSH
• Translational Science, Biomedical MeSH
• Translational Research, Biomedical MeSH
• Artificial Intelligence * MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH