Couples often resemble each other in characteristics like depression, but the reasons for this homogamy (i.e., similarity) remain unclear. We investigated two potential mechanisms: preference for a self-similar partner and convergence (i.e., increasing similarity) over time. In a nationally representative sample of 2,793 Czech individuals who we surveyed three times in one year, we examined self-reports of participants', their ideal partners', and their actual partners' "pessimism and depressiveness". Participants preferred partners less depressive than themselves, yet their actual partners were more depressive than desired. Those who ended their relationships showed a greater ideal-versus-actual partner discrepancy than those who stayed together. In stable relationships, individuals adjusted their ideal preferences to align more closely with their actual partners over time. We identified four relationship classes with latent class growth modeling based on self and partner evaluations: both non-depressive, both depressive, self depressive and partner non-depressive, and self non-depressive and partner depressive. Romantic relationships were most stable when both partners were non-depressive and most likely to dissolve when both were depressive. While we failed to detect convergence overall, we found it within heterogamous (i.e., dissimilar) classes. Overall, our findings suggest that homogamy and heterogamy in depressiveness are complexly associated with relationship maintenance.
- MeSH
- charakteristiky rodiny MeSH
- deprese * psychologie MeSH
- dospělí MeSH
- interpersonální vztahy MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- mladý dospělý MeSH
- sexuální partneři * psychologie MeSH
- zpráva o sobě MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
IntroductionStudy aimed to determine the occurrence of 5 thrombosis-related single-nucleotide polymorphisms (SNPs) in patients with venous thromboembolism (VTE) (n = 2630) and a control group (n = 2637) in the Czech population.MethodsThe following gene SNPs were detected in both groups: F5 Leiden (rs6025), F2 (rs1799963), FGG, fibrinogen gamma' (rs2066865), F11 (rs2289252) and ABO (rs8176719). Statistical analysis was performed using SAS statistical software with population genetics tools.ResultsHeterozygotes for F5 Leiden were associated with a 5.58-fold and homozygotes F5 Leiden with a 33.46-fold increased risk of VTE. At SNP rs1799963 (F2, prothrombin), only heterozygotes had a significant 3.9-fold increased risk of VTE. The findings at SNP rs2066865 (fibrinogen gamma', FGG) showed a 1.37-fold increased risk of VTE for FGG heterozygotes and a 1.77-fold increased risk of VTE for FGG homozygotes. There is also a significant 1.42-fold increase risk of VTE in the heterozygotes and a 1.80-fold increase risk of VTE in the homozygotes of the SNP rs 2289252 (F11). Further higher increases in the risk of VTE in both variants were found in patients with VTE at rs8176719 (ABO, non-O). It corresponds to a 2.2-fold increase in the risk of VTE in heterozygotes and a 3.5-fold increase in the risk of VTE in homozygotes.ConclusionBesides F5 Leiden and prothrombin mutation, the study suggests that the gene polymorphisms of FGG (rs2066865), F11 (rs2289252) and ABO (rs8176719) play a role as an independent heritable risk factor for VTE in the Czech population.
- MeSH
- ABO systém krevních skupin genetika MeSH
- dospělí MeSH
- faktor V * genetika MeSH
- fibrinogen * genetika MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- prevalence MeSH
- protrombin genetika MeSH
- senioři MeSH
- žilní tromboembolie * genetika epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: The number of mobile apps tailored for people living with mental health conditions has increased tremendously. However, the majority of the existing apps are not evidence-based and are being developed by teams without mental health expertise. OBJECTIVE: We aimed to explore psychiatrists' perceptions of what they and their patients need in a mental health app and eventually inform the design of future mobile apps in this area. METHODS: Semi-structured interviews were conducted with psychiatrists (N = 18) from three European countries: Austria, the Czech Republic, and Slovakia. Content analysis using inductive and deductive coding was used to analyze the interviews. RESULTS: Four major themes were deductively identified: current system, gaps in the current system, recommendations for a mobile app, and promoting app use. Psychiatrists provided a comprehensive list of app features they suggested would be helpful. Of particular importance seemed to be enabling patients to self-monitor various aspects of their lives and including an emergency plan. Participants also emphasized that the app should be positive and motivating for patients to use, with some suggesting that users be able to communicate with other users for support. Within the theme of "current system," a common topic was the current shortage of psychiatrists and the feelings of time pressure amongst existing psychiatrists. CONCLUSIONS: The results of this study can be used by software developers to inform future designs of mental health mobile apps, which will hopefully translate to a greater availability of evidence-based apps that address clinical needs.
- Publikační typ
- časopisecké články MeSH
Pleiotropic variants (i.e. genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted 10 years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61 052 variants reported to be associated by at least one genome-wide association study with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16 055 pancreatic ductal adenocarcinoma (PDAC) cases and 212 149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P = 6.52 × 10-5) and 7q36.3-rs288762 (P = 3.03 × 10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell-differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.
- MeSH
- celogenomová asociační studie * MeSH
- duktální karcinom slinivky břišní * genetika MeSH
- genetická pleiotropie * MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- lidské chromozomy, pár 10 genetika MeSH
- lidské chromozomy, pár 7 genetika MeSH
- nádory slinivky břišní * genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Nonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation is believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study in healthy individuals in relation to occupational and smoking-related exposure compared to nonexposed referents. The associations (at P < 10-5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS, and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis, and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, the expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.
- MeSH
- celogenomová asociační studie * MeSH
- chromozomální aberace * MeSH
- interakce genů a prostředí MeSH
- lidé MeSH
- lymfocyty metabolismus MeSH
- nádory genetika MeSH
- oprava DNA genetika MeSH
- poškození DNA MeSH
- pracovní expozice škodlivé účinky MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The epidemiological transition has been characterized by demographic, societal and health changes in societies. Presuming that acute diseases, mostly of communicable etiology, are more important in terms of early-life mortality, whereas chronic diseases are responsible for a greater burden of disease throughout the life course, we attempt to develop an index to measure the stage of the epidemiological transition. Using Global Burden of Diseases, Risk Factors and Injuries (GBD) data available at https://vizhub.healthdata.org/gbd-compare/ on 04/04/2024 to calculate the Epidemiologic Transition Estimate (ETE) index as a ratio of YLD/YLL for the time period of 1990-2019. The values of the index ranged from 0.131 to 1.067 and 0.180 to 2.108 for males and females, respectively, across the 195 included countries. The transition process seems to be faster to females compared to males. The index shows consistently increasing values for five SDI-based country groups, with clear differences among the groups. Although more research and validation studies are needed despite all the uncertainties, the index seems to be robust to assess the progress in epidemiological transition. These findings can help to predict future social care and health system needs to address causes leading to YLD or YLL.
Multidisciplinary molecular tumor boards (MTB) are already well established in many comprehensive cancer centers and play an important role in the individual treatment planning for cancer patients. Comprehensive genomic profiling of tumor tissue based on next-generation sequencing is currently performed for diagnostic and mainly predictive testing. If somatic genomic variants are identified, which are suspected to be pathogenic germline variants (PGVs), MTB propose genetic counseling and germline DNA testing. Commonly used comprehensive genomic profiling approaches of tumor tissue do not include a matched germline DNA control. Therefore, the detection of PGVs could be only predicted based on the content of tumor cells (CTC) in selected tumor area (%) and variant allele frequency score (%). For conclusion, the role of a medical geneticist is essential in these cases. The overall prevalence of PGVs in patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) is approximately 10%. In this single-center study, we present 37 patients with PDAC and 48 patients with CRC who were presented at MTB and tested using the large combined DNA/RNA sequencing panel. Content of tumor cells and variant allele frequency scores were evaluated in all tested patients. In case of suspicion of PGV and no previous genetic testing based on the standard guidelines, genetic counseling was recommended regardless of age, sex, and family history. In the PDAC subgroup, five patients were recommended by MTB for genetic counseling based on suspicious genetic findings. Based on a medical geneticist's decision, germline DNA sequencing was performed in four of these cases, and all of them tested positive for PGV in the following genes: ATM, ATM, BRCA1, and BRCA2. In the CRC subgroup, no PGV was confirmed in the two patients genetically tested based on the MTB recommendations. Furthermore, we present data from our center's registry of patients with PDAC and CRC who underwent genetic counseling and germline DNA testing based on the standard screening criteria. Our data confirm that comprehensive genomic profiling of tumor tissue can identify patients with hereditary forms of PDAC, who could remain unidentified by standard screening for hereditary forms of cancer.
- MeSH
- dospělí MeSH
- duktální karcinom slinivky břišní genetika diagnóza MeSH
- genetické poradenství MeSH
- genetické testování metody MeSH
- genomika metody MeSH
- kolorektální nádory * genetika diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory slinivky břišní * genetika diagnóza MeSH
- náhodný nález MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- zárodečné mutace * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The diagnostic performance of molecular markers in surrogate tissues like stool may be affected by colorectal cancer (CRC) morphological heterogeneity. The mucinous histotype represents a subgroup of CRC with a peculiar molecular program and unfavorable disease progression. However, the percentage of mucinous morphology necessary to define this subtype is still a matter of debate. In this study, we investigated whether stool miRNA profiles of CRC patients differ in patients with mucinous histopathological subtypes compared to non-mucinous cancers. In this respect, we also explored how the stool miRNA signature reported in our previous multicentric study behaves in this histotype. Small-RNA sequencing was performed in fecal and tissue samples of an Italian cohort (n = 172), including 27 CRC with mucinous morphology (mucinous cancers with ≥ 50% mucinous morphology and those with mucinous component ≥ 5% but < 50%), 58 non-mucinous CRC, and 87 colonoscopy-negative controls. Results were compared with fecal miRNA profiles of a cohort from the Czech Republic (n = 98). Most of the differentially expressed (DE) stool miRNAs (n = 324) were in common between CRC with mucinous morphology and non-mucinous histopathological subtypes in comparison with healthy controls. Interestingly, the altered levels of 25 fecal miRNAs previously identified distinguishing CRC cases from controls in both cohorts were also confirmed after stratification for mucinous morphology. Forty-nine miRNAs were DE exclusively in CRC with mucinous morphology and 61 in non-mucinous CRC. Mucinous cancers and those with mucinous component showed fairly similar profiles that were comparable in the Czech cohort. Among the stool DE miRNAs observed in CRC with mucinous morphology, 20 were also altered in the comparison between tumor and adjacent mucosa tissue. This study highlights miRNAs specifically altered in CRC with mucinous morphology. Nevertheless, the performance of our stool miRNA signature in accurately distinguishing CRC cases from controls was not significantly affected by this histological subtype. This aspect further supports the use of stool miRNAs for noninvasive diagnosis and screening strategies.
- MeSH
- feces * chemie MeSH
- kohortové studie MeSH
- kolorektální nádory * genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- mucinózní adenokarcinom * genetika patologie MeSH
- nádorové biomarkery genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
DNA damage is a common event in cells, resulting from both internal and external factors. The maintenance of genomic integrity is vital for cellular function and physiological processes. The inadequate repair of DNA damage results in the genomic instability, which has been associated with the development and progression of various human diseases. Accumulation of DNA damage can lead to multiple diseases, such as neurodegenerative disorders, cancers, immune deficiencies, infertility, and ageing. This comprehensive review delves the impact of alterations in DNA damage response genes (DDR) and tries to elucidate how and to what extent the same traits modulate diverse major human diseases, such as cancer, neurodegenerative diseases, and immunological disorders. DDR is apparently the trait connecting important complex disorders in humans. However, the pathogenesis of the above disorders and diseases are different and lead to divergent consequences. It is important to discover the switch(es) that direct further the pathogenic process either to proliferative, or degenerative diseases. Our understanding of the influence of DNA damage on diverse human disorders may enable the development of the strategies to prevent, diagnose, and treat these diseases. In our article, we analysed publicly available GWAS summary statistics from the NHGRI-EBI GWAS Catalog and identified 12 009 single-nucleotide polymorphisms (SNPs) associated with cancer. Among these, 119 SNPs were found in DDR pathways, exhibiting significant P-values. Additionally, we identified 44 SNPs linked to various cancer types and neurodegenerative diseases (NDDs), including four located in DDR-related genes: ATM, CUX2, and WNT3. Furthermore, 402 SNPs were associated with both cancer and immunological disorders, with two found in the DDR gene RAD51B. This highlights the versatility of the DDR pathway in multifactorial diseases. However, the specific mechanisms that regulate DDR to initiate distinct pathogenic processes remain to be elucidated.
- MeSH
- celogenomová asociační studie MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nádory * genetika MeSH
- nemoci imunitního systému * genetika MeSH
- nestabilita genomu genetika MeSH
- neurodegenerativní nemoci * genetika MeSH
- oprava DNA * genetika MeSH
- poškození DNA * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Chemoresistance represents a major issue affecting cancer therapy efficacy. Because microRNAs (miRNAs) regulate gene expression on multiple levels, their role in chemoresistance development is reasonably certain. In our previous study, miR-122-5p and miR-142-5p were identified as diagnostic, prognostic, and predictive biomarkers for primary and metastatic rectal cancer. The aim of the present study was to investigate whether these miRNAs can also reflect the disease course of patients with colon cancer (CC). Further, we focused on a deeper understanding of their involvement in 5-fluorouracil (5-FU) chemoresistance development.
- MeSH
- chemorezistence * genetika MeSH
- fluoruracil * terapeutické užití farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * genetika krev MeSH
- nádorové biomarkery genetika krev MeSH
- nádory tračníku * genetika farmakoterapie krev patologie MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
