BACKGROUND: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1. METHODS: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. RESULTS: Surveys were emailed to 637 individuals, with responses from 89 ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). CONCLUSIONS: Individuals with ADTKD-MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.
- MeSH
- COVID-19 * mortality genetics MeSH
- Adult MeSH
- Nephritis, Interstitial genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Mucin-1 * blood MeSH
- Mutation * MeSH
- Registries MeSH
- SARS-CoV-2 genetics MeSH
- Aged MeSH
- Uromodulin MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- MeSH
- Humans MeSH
- Point-of-Care Testing * MeSH
- Primary Health Care MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: Monoallelic germline pathogenic variants (GPVs) in five Fanconi anemia (FA) genes (BRCA1/FANCS, BRCA2/FANCD1, PALB2/FANCN, BRIP1/FANCJ, and RAD51C/FANCO) confer an increased risk of breast (BC) and/or ovarian (OC) cancer, but the role of GPVs in 17 other FA genes remains unclear. METHODS: Here, we investigated the association of germline variants in FANCG/XRCC9 with BC and OC risk. RESULTS: The frequency of truncating GPVs in FANCG did not differ between BC (20/10,204; 0.20%) and OC (8/2966; 0.27%) patients compared to controls (6/3250; 0.18%). In addition, only one out of five tumor samples showed loss-of-heterozygosity of the wild-type FANCG allele. Finally, none of the nine functionally tested rare recurrent missense FANCG variants impaired DNA repair activities (FANCD2 monoubiquitination and FANCD2 foci formation) upon DNA damage, in contrast to all tested FANCG truncations. CONCLUSION: Our study suggests that heterozygous germline FANCG variants are unlikely to contribute to the development of BC or OC.
- MeSH
- Adult MeSH
- Genetic Predisposition to Disease * MeSH
- Middle Aged MeSH
- Humans MeSH
- Breast Neoplasms * genetics MeSH
- Ovarian Neoplasms * genetics MeSH
- DNA Repair genetics MeSH
- Fanconi Anemia Complementation Group G Protein * genetics MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Germ-Line Mutation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: Chronic kidney disease (CKD) is a global health issue, ranking as the third leading cause of death worldwide. CKD diagnosis and management depend on clinical laboratory tests, necessitating consistency for precise patient care. Global harmonization of CKD testing through clinical practice guidelines (CPGs) is recommended. Prior to CPG development, assessing the current CKD testing landscape is crucial. In 2022, the European Federation of Laboratory Medicine (EFLM) conducted an online survey among European laboratories associated with EFLM, evaluating CKD testing practices, including new glomerular filtration rate (GFR) estimation methods. This report summarizes the 2022 survey findings and offers recommendations for improving CKD test standardization. METHODS: An online survey was conducted in November 2022 using a questionnaire hosted on LimeSurvey sent to European laboratories affiliated with the EFLM. The survey results were recorded in Excel files and analysed. RESULTS: The results highlight significant discrepancies among countries in unit expression, methods, cystatin C use, and GFR calculation equations. Additionally, limited attention to pediatric renal biology specifics, varied proteinuria and albuminuria result expressions, and limited awareness of GFR measurement methods through iohexol clearance are noted. CONCLUSIONS: In an effort to enhance the standardization of crucial biomarkers utilized in nephrology for evaluating renal function and diagnosing kidney injuries, the EFLM Task Group on CKD suggests nine practical recommendations tailored for European laboratories. The group is confident that implementing these measures will minimize result expression discrepancies, ultimately leading to enhanced patient care.
- MeSH
- Biomarkers MeSH
- Renal Insufficiency, Chronic * diagnosis MeSH
- Child MeSH
- Glomerular Filtration Rate MeSH
- Creatinine metabolism MeSH
- Laboratories * MeSH
- Humans MeSH
- Surveys and Questionnaires MeSH
- Kidney Function Tests methods MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
Tau protein je jedním z neurocytoskeletálních proteinů podílejících se na patogenezi závažných neurologických onemocnění, zejména Alzheimerovy nemoci. Vyznačuje se značnou strukturní variabilitou, která se odráží v existenci jeho četných proteoforem. Tento přehled si klade za cíl poskytnout stručné informace o struktuře tau proteinu a jeho proteoformách, které se zdají být perspektivní jako biomarkery pro klinické použití. Jsou diskutovány biologické tekutiny vhodné pro laboratorní vyšetření v klinické praxi, tj. mozkomíšní mok a krev (plazma/sérum). Celkový tau protein a jeho fosforylované formy (hlavně protein pT181-tau, fosforylovaný na threoninovém zbytku 181) již našly klinické uplatnění v diagnostice Alzheimerovy nemoci.
The tau protein is one of the neurocytoskeletal proteins that participate in the pathogenesis of serious neurological diseases, especially Alzheimer's disease. The tau protein is characterized by considerable structural variability, which is reflected in the existence of its numerous proteoforms. This review aims to provide brief information on the structure of tau protein and its proteoforms, which seem promising biomarkers for clinical use. Biological fluids, suitable for laboratory examination in clinical practice, i.e., cerebrospinal fluid and blood (plasma/serum), are discussed. Total tau protein and its phosphorylated forms (mainly the pT181-tau protein, phosphorylated at the threonine residue 181) have already found clinical application in diagnosis of Alzheimer's disease.
The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of in vitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning in vitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine" (Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future.
- MeSH
- Laboratories, Clinical * economics trends MeSH
- Clinical Laboratory Techniques economics trends MeSH
- Congresses as Topic MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Folia Biologica celebrates 70 years of continuous publication of research papers. The first volume was published in Prague in 1954 on behalf of the Institute of Molecular Genetics of the Czechoslovak Academy of Sciences (since 1990 the Academy of Sciences of the Czech Republic) under the subtitle "International edition of the journal Czechoslovakian Biology". Born in the dark days of the Cold War, Folia Biologica provided a thin but important link between the politically controlled science behind the Iron Curtain in the former Czechoslovakia and that of the free Western world. Initially, the journal focused on research papers in the fields of experimental medicine, immunology, virology, and experimental zoology. Since 1961 (Volume 7), Folia Biologica has been indexed in the Web of Science database. The first issue of Volume 7 was introduced by a review article by Peter Brian Medawar (1915-1987), winner of the 1960 Nobel Prize in Physiology or Medicine "for the discovery of acquired immunological tolerance", which is reprinted in this anniversary issue [1].In the late 1960s, during the political relaxation that culminated in the Prague Spring, cooperation with free Western science intensified and enabled a lively scientific dialogue between Czechoslovak and foreign biological scientists, namely immunologists, molecular biologists, and virologists, as illustrated by a series of original research articles from Folia Biologica by Georg Davis Snell (1903-1996) and Jean Dausset (1916-2009), who were awarded the Nobel Prize in Physiology and Medicine in 1980 "for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions", which led to the discovery of the major histocompatibility system (MHC) [2-7]. Another powerful example is an article in Folia Biologica by François Jacob (1920-2013), who was awarded the Nobel Prize in 1965 for discoveries that helped elucidate the transcriptional control of enzyme levels [8].Despite the years of political repression during the "normalization" period following the invasion of the Warsaw Pact troops into Czechoslovakia in 1968, the scientists and editors of Folia Biologica from the Academy of Sciences were able to maintain vibrant contacts with the world's leading scientists. In 1981, the journal changed its subtitle to "Journal of Cellular and Molecular Biology". In 1983, Folia Biologica published the article by Renato Dulbecco (1914-2012), who was awarded the Nobel Prize in 1975 for "discoveries concerning the interaction between tumor viruses and the genetic material of the cell"[9].With further orientation towards human molecular medicine, the journal entered the era after the Velvet Revolution in 1989, which represented the desired end of political control over national science. The interest of Czechoslovak and Czech scientists in publishing in Folia Biologica began to decline at the end of the 1990s, when they had at their disposal the full range of scientific journals from all over the world. Since volume 63 (January 2006), Folia Biologica has been published by the First Faculty of Medicine, Charles University, Prague, in a fully open access model.With the new decade that begins with this issue, the journal has undergone a series of improvements, including the strengthening of the editorial board, the assignment of a DOI (Digital Object Identifier) number to each article, the improvement of the cover layout and graphics, the innovation of the website, and a more precise definition of the journal's aim. Folia Biologica now publishes articles describing original research aimed at elucidating a wide range of issues in biomedicine, especially in oncology and human molecular genetics. In addition, the journal focuses on the cellular and molecular mechanisms of disease and provides studies on all organisms, cells and tissues that serve as biological and disease models, as well as clinical and translational research studies. Further improvements towards sustainable and rapid publication will be accomplished by introducing an online-only publication model planned for 2025.To celebrate the 70th anniversary of Folia Biologica, we begin the anniversary volume with the reprint of Sir Peter Brian Medawar's review. To commemorate the continuing history of the journal, and to thank our predecessors and contributors, we present the title pages, table of contents, and editorial boards of Folia Biologica by decade, illustrating the changes in research focus, human knowledge, and the evolution of the journal.We would like to thank all authors, reviewers, editorial board members, editors and managing editors involved in the journal production in the past decades, namely Ivan Málek, Milan Hašek, Alena Langerová, Josef Říman, Jan Bubeník, Jan Svoboda, Emanual Nečas, Karel Smetana Jr. and Zdeněk Kostrouch, for their commitment and dedication to Folia Biologica.We wish our journal many more decades of scientifically interesting articles, publishing open-minded science by excellent authors for the pleasure of satisfied readers!
- MeSH
- History, 20th Century MeSH
- History, 21st Century MeSH
- Humans MeSH
- Periodicals as Topic * history MeSH
- Anniversaries and Special Events MeSH
- Check Tag
- History, 20th Century MeSH
- History, 21st Century MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Editorial MeSH
- Geographicals
- Czech Republic MeSH
- Czechoslovakia MeSH
BACKGROUND: The polygenic risk score (PRS) allows the quantification of the polygenic effect of many low-penetrance alleles on the risk of breast cancer (BC). This study aimed to evaluate the performance of two sets comprising 77 or 313 low-penetrance loci (PRS77 and PRS313) in patients with BC in the Czech population. METHODS: In a retrospective case-control study, variants were genotyped from both the PRS77 and PRS313 sets in 1329 patients with BC and 1324 noncancer controls, all women without germline pathogenic variants in BC predisposition genes. Odds ratios (ORs) were calculated according to the categorical PRS in individual deciles. Weighted Cox regression analysis was used to estimate the hazard ratio (HR) per standard deviation (SD) increase in PRS. RESULTS: The distributions of standardized PRSs in patients and controls were significantly different (p < 2.2 × 10-16) with both sets. PRS313 outperformed PRS77 in categorical and continuous PRS analyses. For patients in the highest 2.5% of PRS313, the risk reached an OR of 3.05 (95% CI, 1.66-5.89; p = 1.76 × 10-4). The continuous risk was estimated as an HRper SD of 1.64 (95% CI, 1.49-1.81; p < 2.0 × 10-16), which resulted in an absolute risk of 21.03% at age 80 years for individuals in the 95th percentile of PRS313. Discordant categorization into PRS deciles was observed in 248 individuals (9.3%). CONCLUSIONS: Both PRS77 and PRS313 are able to stratify individuals according to their BC risk in the Czech population. PRS313 shows better discriminatory ability. The results support the potential clinical utility of using PRS313 in individualized BC risk prediction.
- MeSH
- Adult MeSH
- Genetic Predisposition to Disease * MeSH
- Genetic Risk Score MeSH
- Risk Assessment methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Multifactorial Inheritance genetics MeSH
- Breast Neoplasms * genetics MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
Lipidome perturbation occurring during meta-inflammation is associated to left ventricle (LV) remodeling though the activation of the NLRP3 inflammasome, a key regulator of chronic inflammation in obesity-related disorders. Little is known about phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as DAMP-induced NLRP3 inflammasome. Our study is aimed to evaluate if a systemic reduction of PC/PE molar ratio can affect NLRP3 plasma levels in cardiovascular disease (CVD) patients with insulin resistance (IR) risk. Forty patients from IRCCS Policlinico San Donato were enrolled, and their blood samples were drawn before heart surgery. LV geometry measurements were evaluated by echocardiography and clinical data associated to IR risk were collected. PC and PE were quantified by ESI-MS/MS. Circulating NLRP3 was quantified by an ELISA assay. Our results have shown that CVD patients with IR risk presented systemic lipid impairment of PC and PE species and their ratio in plasma was inversely associated to NLRP3 levels. Interestingly, CVD patients with IR risk presented LV changes directly associated to increased levels of NLRP3 and a decrease in PC/PE ratio in plasma, highlighting the systemic effect of meta-inflammation in cardiac response. In summary, PC and PE can be considered bioactive mediators associated to both the NLRP3 and LV changes in CVD patients with IR risk.
- MeSH
- Phosphatidylcholines * blood MeSH
- Phosphatidylethanolamines * blood metabolism MeSH
- Inflammasomes * metabolism MeSH
- Insulin Resistance * MeSH
- Cardiovascular Diseases * blood pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- NLR Family, Pyrin Domain-Containing 3 Protein * metabolism MeSH
- Ventricular Remodeling * MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
