A double primary colorectal cancer (CRC) in a familial setting signals a high risk of CRC. In order to identify novel CRC susceptibility genes, we whole-exome sequenced germline DNA from nine persons with a double primary CRC and a family history of CRC. The detected variants were processed by bioinformatics filtering and prioritization, including STRING protein-protein interaction and pathway analysis. A total of 150 missense, 19 stop-gain, 22 frameshift and 13 canonical splice site variants fulfilled our filtering criteria. The STRING analysis identified 20 DNA repair/cell cycle proteins as the main cluster, related to genes CHEK2, EXO1, FAAP24, FANCI, MCPH1, POLL, PRC1, RECQL, RECQL5, RRM2, SHCBP1, SMC2, XRCC1, in addition to CDK18, ENDOV, ZW10 and the known mismatch repair genes. Another STRING network included extracellular matrix genes and TGFβ signaling genes. In the nine whole-exome sequenced patients, eight harbored at least two candidate DNA repair/cell cycle/TGFβ signaling gene variants. The number of families is too small to provide evidence for individual variants but, considering the known role of DNA repair/cell cycle genes in CRC, the clustering of multiple deleterious variants in the present families suggests that these, perhaps jointly, contributed to CRC development in these families.
- MeSH
- Adult MeSH
- Genetic Predisposition to Disease * MeSH
- Colorectal Neoplasms * genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- DNA Repair genetics MeSH
- Pedigree MeSH
- Exome Sequencing * methods MeSH
- Aged MeSH
- Germ-Line Mutation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Purpose: Monkeypox, an orthopoxvirus with zoonotic origins, has emerged as a global health concern due to recent outbreaks outside of endemic regions. Pregnant and lactating individuals are particularly vulnerable to potential complications, emphasizing the need for targeted prevention and management approaches. Methods: This review explores the clinical presentation, impact, diagnostic methods, and treatment options for monkeypox in pregnant and lactating populations, with a focus on safety, effectiveness, and prevention strategies. Results: The review synthesizes current literature on monkeypox, specifically addressing supportive care, antiviral therapy, natural remedies, vaccination, and infection control practices. Special considerations for maternal and fetal health are discussed, along with preventive guidelines to minimize transmission risks. Supportive care is the primary management approach, with antivirals like Tecovirimat and Brincidofovir considered in severe cases. Conclusion: While vaccination offers preventive protection, strict hygiene and protective measures are crucial in healthcare and community settings. For lactating mothers, expressed milk and alternative feeding methods can mitigate transmission risks. Effective management of monkeypox in pregnant and lactating individuals requires a balanced approach that prioritizes maternal and infant safety. Further targeted research is needed to identify the specific impact of the virus on pregnancy outcomes and breastfeeding practices.
Úvod: Incidence věkově předčasného kolorektálního karcinomu (KRK) celosvětově stoupá. V České republice je aktuálně věková hranice pro celopopulační screening KRK 50 let. Zvažuje se snížení věkové hranice, ale to v praxi naráží na omezenou kapacitu endoskopických pracovišť. Cílem práce bylo zhodnotit riziko nálezu neoplastické léze dle věkových skupin a pohlaví. Metodika: Jedná se o retrospektivní observační studii provedenou v Beskydském gastrocentru v Nemocnici ve Frýdku-Místku v letech 2017–2023. V tomto období byla sledována incidence neoplastických lézí ve věkových skupinách 30–34 let, 35–39 let, 40–44 let, 45–49 let, 50–54 let, 55–59 let, zvlášť pro muže a ženy. K porovnání dvou kategorických proměnných byl použit Chí kvadrát test; p < 0,05 bylo považováno za signifikantní. Výsledky: Za sledované období bylo provedeno celkem 13 352 koloskopií, 7 094 u mužů, 6 258 u žen, 2 678 u pacientů < 50 let, 10 674 u pacientů ≥ 50 let. Charakteristiky pacientů a incidence neoplastických lézí v jednotlivých pětiletých věkových skupinách jsou zobrazeny v tabulkách níže v tomto textu. Incidence neoplastických lézí v každé pětileté věkové skupině byla vždy významně vyšší než v předcházející mladší věkové skupině. Pokud jako referenční skupinu s nejnižším výskytem neoplastických lézí, u které je v současnosti v ČR doporučen screening KRK, bereme ženy 50–54 let, mají statisticky srovnatelné riziko jak muži 45–49 let (p = 0,304), tak muži 40–44 let (p = 0,086). Ženy 45–49 let (p = 0,001) mají statisticky signifikantně nižší riziko než ženy 50–54 let. Závěry: Pokud bychom měli snižovat věkovou hranici pro screening KRK v ČR postupně tak, abychom nezahltili kapacitu endoskopických center, jsou v nejvyšším riziku muži 45–49 let, poté muži 40–44 let a až poté ženy 45–49 let. Samozřejmostí je surveillance osob s rodinným rizikem KRK a časný termín endoskopického vyšetření pro symptomatické pacienty.
Background: Early onset colorectal cancer (CRC; cancer in a person younger than 50 years) has increasing incidence in the last few years. Current age limit for population screening in Czech Republic is 50 years of age. Lowering the age limit is necessary, but this collides with limited capacity of endoscopy units. The aim of our study was to evaluate the risk of neoplastic lesions according to age and gender. Methods: It was an observational retrospective study conducted in a non-university hospital Frýdek-Místek between 2017 and 2023. The incidence of all neoplastic lesions was evaluated in age groups 30–34, 35–39, 40–44, 45–49, 50–54, and 55–59 years separately for men and women. Two dichotomous variables were compared using the Chi square test, where P <0.05 was considered significant. Results: During the study period, 13,352 colonoscopies were done in total (7,094 men, 6,258 women); 2,678 in patients <50 years of age, and 10,674 in patients ≥50 years. The incidence of all neoplastic lesions in each age group was always significantly higher than in the previous age group, the results are shown in the tables below in this text. As we determined the reference group of women 50–54 years of age as the group with the lowest risk of neoplastic lesions currently involved in population screening, the comparable risk of all neoplastic lesions was observed for men 45–49 years of age (P = 0.304) and also for men 40–44 years of age (P = 0.086). Women 45–49 years of age (P = 0.001) have a significantly lower risk of advanced neoplastic lesions than women 50–54 years of age. Conclusions: If we do not want to overload the capacity of endoscopy units, we should lower the age limit for population screening by age and gender groups. According to our retrospective data, the highest risk of neoplastic lesions is found in men 45–49 years of age, and after them men 40–44 years of age. Women 45–49 years of age have a significantly lower risk of CRC.
- MeSH
- Early Detection of Cancer methods statistics & numerical data MeSH
- Adult MeSH
- Colorectal Neoplasms * diagnosis etiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Retrospective Studies MeSH
- Risk Factors * MeSH
- Sex Factors MeSH
- Preventive Health Services methods MeSH
- Age Factors MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
OBJECTIVE: Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. METHODS: We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. RESULTS: Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation. CONCLUSION: Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.
BACKGROUND: The war in Ukraine has led to significant migration to neighboring countries, raising public health concerns. Notable tuberculosis (TB) incidence rates in Ukraine emphasize the immediate requirement to prioritize approaches that interrupt the spread and prevent new infections. METHODS: We conducted a prospective genomic surveillance study to assess migration's impact on TB epidemiology in the Czech Republic and Slovakia. Mycobacterium tuberculosis isolates from Ukrainian war refugees and migrants, collected from September 2021 to December 2022 were analyzed alongside 1574 isolates obtained from Ukraine, the Czech Republic, and Slovakia. RESULTS: Our study revealed alarming results, with historically the highest number of Ukrainian tuberculosis patients detected in the host countries. The increasing number of cases of multidrug-resistant TB, significantly linked with Beijing lineage 2.2.1 (p < 0.0001), also presents substantial obstacles to control endeavors. The genomic analysis identified the three highly related genomic clusters, indicating the recent TB transmission among migrant populations. The largest clusters comprised war refugees diagnosed in the Czech Republic, TB patients from various regions of Ukraine, and incarcerated individuals diagnosed with pulmonary TB specialized facility in the Kharkiv region, Ukraine, pointing to a national transmission sequence that has persisted for over 14 years. CONCLUSIONS: The data showed that most infections were likely the result of reactivation of latent disease or exposure to TB before migration rather than recent transmission occurring within the host country. However, close monitoring, appropriate treatment, careful surveillance, and social support are crucial in mitigating future risks, though there is currently no evidence of local transmission in EU countries.
- MeSH
- Adult MeSH
- Incidence MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Molecular Epidemiology * MeSH
- Tuberculosis, Multidrug-Resistant epidemiology MeSH
- Mycobacterium tuberculosis * genetics isolation & purification MeSH
- Transients and Migrants * statistics & numerical data MeSH
- Armed Conflicts MeSH
- Prospective Studies MeSH
- Tuberculosis * epidemiology transmission MeSH
- Refugees * statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
- Ukraine MeSH
BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by pervasive personality and behavioural disturbances with severe impact on patients and caregivers. In current clinical practice, treatment is based on nonpharmacological and pharmacological approaches. Unfortunately, trial-based evidence supporting symptomatic pharmacological treatment for the behavioural disturbances in FTD is scarce despite the significant burden this poses on the patients and caregivers. METHOD: The study examined drug management decisions for several behavioural disturbances in patients with FTD by 21 experts across European expert centres affiliated with the European Reference Network for Rare Neurological Diseases (ERN-RND). RESULTS: The study revealed the highest consensus on drug treatments for physical and verbal aggression, impulsivity and obsessive delusions. Antipsychotics (primarily quetiapine) were recommended for behaviours posing safety risks to both patients and caregivers (aggression, self-injury and self-harm) and nightly unrest. Selective serotonin reuptake inhibitors were recommended for perseverative somatic complaints, rigidity of thought, hyperphagia, loss of empathy and for impulsivity. Trazodone was specifically recommended for motor unrest, mirtazapine for nightly unrest, and bupropion and methylphenidate for apathy. Additionally, bupropion was strongly advised against in 10 out of the 14 behavioural symptoms, emphasizing a clear recommendation against its use in the majority of cases. CONCLUSIONS: The survey data can provide expert guidance that is helpful for healthcare professionals involved in the treatment of behavioural symptoms. Additionally, they offer insights that may inform prioritization and design of therapeutic studies, particularly for existing drugs targeting behavioural disturbances in FTD.
- MeSH
- Aggression drug effects MeSH
- Antipsychotic Agents therapeutic use MeSH
- Frontotemporal Dementia * drug therapy MeSH
- Impulsive Behavior drug effects MeSH
- Consensus MeSH
- Humans MeSH
- Selective Serotonin Reuptake Inhibitors therapeutic use MeSH
- Rare Diseases drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).
Onkologické ochorenie kože zostáva významným problémom verejného zdravia a predstavuje značnú záťaž pre systém zdravotnej starostlivosti na celom svete. Vzhľadom na vysokú mieru výskytu, ktorá neustále zvyšuje náklady na zdravotnú starostlivosť, existuje naliehavá potreba uprednostniť zlepšenie preventívnych programov zameraných na boj proti tomuto rastúcemu problému. Posilnenie preventívnych opatrení je prvoradé pri zmierňovaní záťaže, ktorú v systéme zdravotnej starostlivosti predstavuje onkologické ochorenie kože. Podporovaním povedomia o rizikových faktoroch, presadzovaním postupov včasnej detekcie a podporovaním správania bezpečného pred UV žiarením, umožňuje práve správna prevencia podniknúť proaktívne kroky na ochranu zdravia kože. Popisovaný prípad sa zaoberá 70-ročným pacientom prijatým k odstráneniu nádorovej lézie v nazálnom regione a následnú rekonštrukciu defektu posuvným V-Y lalokom k jeho uzatvoreniu.
Skin cancer remains a significant public health concern, imposing a substantial burden on healthcare systems worldwide. With its high incidence rates continuously driving up healthcare costs, there is a pressing need to prioritize the improvement of preventive programs dedicated to combating this growing problem. Enhancing preventive measures is paramount in alleviating the strain placed on healthcare systems by skin cancer. By promoting awareness of risk factors, advocating for early detection practices, and encouraging UV-safe behaviors, preventive initiatives empower individuals to take proactive steps in safeguarding their skin health. The case discusses a 70-years old patient who came for excision of cancerous lesion in the nasal area followed by reconstruction with V-Y advancement flap for closure of the defect.
- MeSH
- Carcinoma, Basal Cell * surgery MeSH
- Surgical Flaps MeSH
- Nasal Surgical Procedures methods MeSH
- Humans MeSH
- Interdisciplinary Communication MeSH
- Skin Neoplasms * surgery prevention & control MeSH
- Nose Neoplasms surgery MeSH
- Aged MeSH
- Preventive Health Services classification methods MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Karcinom ovaria je onemocnění s vysokým podílem hereditární formy. V předcházejícím projektu zabývajícím se analýzou panelu genů u pacientek s karcinomem ovaria a populačně specifických kontrol jsme u velmi mladých pacientek detekovali překvapivě nízkou frekvenci patogenních mutací v genech se známou/předpokládanou asociací s karcinomem ovaria. U pacientek s diagnózou karcinomu ovaria do 30 let byla frekvence mutací v 18 predispozičních genech 15,5%, zatímco frekvence mutací v celém souboru (medián věku 53,7 let) dosahovala 34,7%. V navrhovaném projektu plánujeme provést sekvenování exomu/genomu v dobře charakterizovaném souboru žen s diagnózou karcinomu ovaria do 30 let doplněné o analýzu panelu genů na úrovni RNA a u nenádorových kontrol starších 60 let. Nalezené alterace budou po prioritizaci a konfirmaci dále analyzovány u dalších vysoce rizikových podskupin pacientek s karcinomem ovaria a u neselektovaných kontrol. Možný klinický výstup projektu a případné zařazení dalších genů/oblastí do používaných diagnostických panelů bude diskutováno v odborných společnostech.; Ovarian cancer is a disease with a high proportion of hereditary form. In the preceding project analyzing a gene panel in ovarian cancer patients and population-matched controls, we identified the surprisingly low frequency of mutations in genes with known/anticipated predisposition to ovarian cancer in patients diagnosed with ovarian cancer before the age of 30. Whereas mutation frequency in 18 predisposition genes in these very young patients was 15,5%, mutation frequency in the whole cohort (median age 53,7 years) reached 34,7%. In the proposed project, we aim to perform exome/genome sequencing together with gene panel RNA sequencing in the well-characterized group of women diagnosed with ovarian cancer before the age of 30 and in non-cancer controls older 60 years. After prioritization and confirmation, identified alterations will be further analyzed in other high-risk ovarian cancer patients and in unselected controls. Possible clinical use or inclusion of further regions or gene(s) into diagnostic gene panels will be discussed in Medical Associations.
- Keywords
- Ovarian cancer, DNA, DNA, RNA, RNA, nádorová predispozice, exom, exome, cancer predisposition, karcinom ovaria, next gen sekvenování, next gen sequencing,
- NML Publication type
- závěrečné zprávy o řešení grantu AZV MZ ČR
INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors. RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). DISCUSSION: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. HIGHLIGHTS: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.
