OBJECTIVES: This study aims to explore the lasting effects of stress experienced by pregnant women during World War II (WWII) on body and head measurements of their adult daughters. METHODS: The research sample consists of 336 female university students born in Poland between 1925 and 1951. The data include body measurements and socioeconomic information (parental occupation and number of siblings) acquired from questionnaires collected between the 1950s and 1970s. Student's t-test, Mann-Whitney test and Analysis of Variance were used to analyze differences in body measurements between groups of women born before and during the war, as well as the possible influences of socioeconomic variables. RESULTS: The mean measurements of body height, symphysion height, and waist circumference were lower in women conceived and born during the war compared to those born in the pre-war period. In contrast, the mean measurements of biacromial (shoulder) width, trunk length, and three head dimensions were higher in women conceived and born during the war. Additionally, the number of siblings appeared to be a significant factor that may have influenced the body measurements of women in both groups. For instance, a higher number of living siblings, particularly sisters, was associated with reduced body dimensions, such as body height and waist circumference, while a greater number of deceased siblings was linked to an increase in certain body dimensions. CONCLUSION: The results suggest that war-related prenatal conditions may have influenced the postnatal growth and development of women conceived and born during the war. Notably, the direction of these changes varied, which indicates that the growth response to the war-related conditions was a complex adaptation, reflecting both positive and negative changes in different body parts, rather than a uniform pattern of growth suppression.

• MeSH
• 2. světová válka * MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• psychický stres MeSH
• socioekonomické faktory MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Polsko MeSH

BACKGROUND: Increased lung cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately and by multiple quantitative bias analyses, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased the direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung cancer risk in the multiple bias analysis. Lung cancer risks remained increased for lower SES groups, with higher risks in men (fourth vs. first [highest] SES quartile: CDE, 1.50 [SI, 1.32, 1.69]) than women (CDE: 1.20 [SI: 1.01, 1.45]). Natural direct effects were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.

• MeSH
• analýza mediace * MeSH
• dospělí MeSH
• kouření * epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• nádory plic * epidemiologie   MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• senioři MeSH
• společenská třída * MeSH
• studie případů a kontrol MeSH
• zkreslení výsledků (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

BACKGROUND: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. OBJECTIVES: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime. METHODS: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis. RESULTS: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up. CONCLUSION: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.

• MeSH
• Aspirin * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• extracelulární vezikuly * metabolismus   účinky léků   MeSH
• inhibitory agregace trombocytů * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inhibitory faktoru Xa * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci * krev   prevence a kontrola   farmakoterapie   MeSH
• kombinovaná farmakoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• prospektivní studie MeSH
• proteomika metody   MeSH
• rivaroxaban * aplikace a dávkování   MeSH
• senioři MeSH
• trombóza krev   prevence a kontrola   farmakoterapie   MeSH
• výsledek terapie MeSH
• zánět krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Randomized clinical trials demonstrated similar efficacy and improved safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation (AF). Long-term data in routine clinical practice are needed. HYPOTHESIS: Patients with AF receiving edoxaban at baseline continue to have low annualized effectiveness and safety event rates in the second year of follow-up, with regional variations observed. METHODS: The Global ETNA-AF program is a prospective, noninterventional study of patients with AF receiving edoxaban. Patient characteristics and annualized clinical event rates were assessed overall and by region across the 2-year follow-up. Annualized event rates of bleeding and thromboembolic events were assessed within the first year and conditionally in patients who were event-free up to 12 months in the second year. RESULTS: This analysis comprised 26 805 patients from Europe (n = 13 164), Japan (n = 10 342), and non-Japanese Asian regions (n = 3299). Patients from Europe had the highest burden of comorbidities. The annualized event rates for major bleeding, any stroke, all-cause death, and cardiovascular death varied by region. The global annualized event rates in the first and second year were 1.31%/year and 0.86%/year for major bleeding, 1.06%/year and 0.65%/year for any stroke, 0.84%/year and 0.73%/year for cardiovascular death, and 3.05%/year and 3.18%/year for all-cause death. CONCLUSION: Annualized event rates for any stroke and major bleeding remained low through 2-year follow-up for patients with AF receiving edoxaban at baseline. Differences in annualized event rates for all-cause and cardiovascular mortality between Europe, Japan, and non-Japanese Asian regions may reflect variations in baseline characteristics. TRIAL REGISTRATION: Europe, NCT02944019; Japan, UMIN000017011; Korea/Taiwan, NCT02951039; Hong Kong, NCT03247582; and Thailand, NCT03247569.

• MeSH
• časové faktory MeSH
• cévní mozková příhoda prevence a kontrola   epidemiologie   etiologie   MeSH
• fibrilace síní * farmakoterapie   komplikace   MeSH
• incidence MeSH
• inhibitory faktoru Xa * terapeutické užití   škodlivé účinky   MeSH
• krvácení * chemicky indukované   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prospektivní studie MeSH
• pyridiny * terapeutické užití   škodlivé účinky   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thiazoly * terapeutické užití   škodlivé účinky   MeSH
• tromboembolie prevence a kontrola   epidemiologie   etiologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

The precise and unambiguous detection and quantification of internal RNA modifications represents a critical step for understanding their physiological functions. The methods of direct RNA sequencing are quickly developing allowing for the precise location of internal RNA marks. This detection is, however, not quantitative and still presents detection limits. One of the biggest remaining challenges in the field is still the detection and quantification of m6A, m6Am, inosine, and m1A modifications of adenosine. The second intriguing and timely question remaining to be addressed is the extent to which individual marks are coregulated or potentially can affect each other. Here, we present a methodological approach to detect and quantify several key mRNA modifications in human total RNA and in mRNA, which is difficult to purify away from contaminating tRNA. We show that the adenosine demethylase FTO primarily targets m6Am marks in noncoding RNAs in HEK293T cells. Surprisingly, we observe little effect of FTO or ALKBH5 depletion on the m6A mRNA levels. Interestingly, the upregulation of ALKBH5 is accompanied by an increase in inosine level in overall mRNA.

• MeSH
• adenosin * analogy a deriváty   metabolismus   genetika   analýza   MeSH
• alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 * metabolismus   genetika   MeSH
• chromatografie kapalinová metody   MeSH
• gen pro FTO * metabolismus   genetika   MeSH
• HEK293 buňky MeSH
• inosin * metabolismus   genetika   MeSH
• kapalinová chromatografie-hmotnostní spektrometrie MeSH
• lidé MeSH
• messenger RNA * genetika   metabolismus   MeSH
• posttranskripční úpravy RNA MeSH
• tandemová hmotnostní spektrometrie * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: A comparison of body composition assessments using military circumferences to bioelectrical impedance analysis (BIA) and the reference standard dual-energy X-ray absorptiometry (DEXA) can gauge effectiveness of assessments. High-frequency (500 KHz) direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA) accurately calculates total water mass and body fat% (BF%), but it is unknown whether higher frequencies (1,000 KHz) increase measurement accuracy. The purpose was to compare DSM-BIA 500, DSM-BIA 1000, the DoD Circumference Method (CM), and the reference-standard DEXA. MATERIALS AND METHODS: Design: Cross sectional, observational study. Participants/Setting: A total of 62 participants from the military healthcare system (n = 25 males, 38.8 ± 11.4 years, n = 37 females 43.7 ± 15.95 years) were measured in an outpatient clinic setting. Statistical Analysis: BF% was estimated via DEXA, DSM-BIA 500, DSM-BIA 1000, and CM to identify the relationship between methods using Pearson correlation, intraclass correlation coefficients (ICCs), and Bland-Altman plots. The study was approved by the IRB from Walter Reed National Military Medical Center at Bethesda and Concordia University Chicago. RESULTS: Circumference Method BF% was moderately correlated with DSM-BIA 500 (males r = 0.63, ICC = 0.76; females r = 0.77, ICC = 0.85), DSM-BIA 1000 (males r = 0.59, ICC = 0.74; females r = 0.77, ICC = 0.85), and DEXA (males r = 0.62, ICC = 0.62; females r = 0.73, ICC = 0.82). DSM-BIA 500 BF% was strongly correlated with DSM-BIA 1000 (males r = 0.99, ICC = 0.99; females r = 0.99, ICC = 0.99) and DEXA (males r = 0.93, ICC = 0.94; females r = 0.89, ICC = 0.89). Lastly, DSM-BIA 1000 BF% was also strongly correlated with DEXA (males r = 0.93, ICC = 0.94; females r = 0.84, ICC = 0.90) (P for each reported r < 0.01). Bland-Altman analysis confirmed an overall mean bias of -1.72% CM vs. DEXA in females, indicating the tendency of CM to underestimate BF% compared to DEXA limits of agreement from -14.24 to 10.8. There was an upward slope of the linear relationship between the bias and mean of the measures (Beta = 0.34, P = 0.01). In the full cohort, there was an overall mean bias of 1.14% of CM vs. DSM BIA 1000, with CM tending to overestimate BF% compared to DSM BIA 1000 with limits of agreement -11.13 to 13.41%. There is an upward slope line of the linear relationship between the bias and the mean of the measures (Beta = 0.17, P = .03). CONCLUSION: This study found that CM BF% was moderately correlated with DSM-BIA 500 kHz, DSM-BIA 1,000 kHz BIA, and DEXA. Both DSM-BIA 500 and DSM-BIA 1,000 kHz strongly correlated well with DEXA implying that there was no further increase in correlation with increased frequency. Additionally, there was proportional bias in BF% in the female group between CM and DEXA and in the total group between CM and DSM BIA 1000.

• MeSH
• absorpční fotometrie * metody   statistika a číselné údaje   MeSH
• dospělí MeSH
• elektrická impedance * MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• složení těla * fyziologie   MeSH
• tuková tkáň diagnostické zobrazování   fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH

BACKGROUND: The Swedish Family-Cancer Database (FCD) is the largest source of data on familial cancer in the world, including practically complete family structures and individual cancer diagnoses from the high-quality cancer registry. We present a novel application of FCD by analyzing age-specific familial risks and interpreting them through likely causes, such as germline pathogenic variants and/or environmental exposures. MAIN BODY: The basic assumption for this approach is that a discrete familial clustering in a narrow age-interval is not random but may provide causal clues. For this analysis we selected reasonably common cancers to meaningfully scrutinize familial risk through adulthood in which cancers are diagnosed, that included colorectal (CRC) and endometrial cancers, prostate and kidney cancers and breast and lung cancers. The interpretation is based on the literature. The highest familial relative risks for CRC and endometrial cancers were found at ages 40-44 years, matching the peak impact of mismatch repair gene mutations. However endometrial cancer showed also a small early onset component which could not be explained. Age-related familial risks for breast, prostate and kidney cancers also matched data from large-scale sequencing; these included the early onset component in kidney cancer which was likely due to VHL mutations. Age distribution of familial lung cancer was unique in showing a wide peak extending from middle to old ages, which would be consistent with a combination of direct genetic effects and indirect influence on inheritance of smoking dependence. CONCLUSIONS: The present review of age-specific familial risks and age-of-onset data from the literature may allow an interpretation that the familial and germline landscapes are reasonably harmonious for relatively early onset cancers but at higher ages no discrete peaks can be found which may implicate attenuated impact of high-risk genes and polygenic influence.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Childlessness, as well as having a high number of children, has been reported to be associated with an elevated risk of dementia compared to having 2-3 children. The mechanisms underlying these relationships are not well understood and may be mediated by different midlife risk factors. We examined the mediating role of various factors on the relationship between the number of children and dementia risk. These factors include socioeconomic factors (e.g., occupational complexity), psychosocial (e.g.., social activities, loneliness, life satisfaction), lifestyle (e.g., smoking, physical inactivity, alcohol intake), and chronic diseases (e.g., obesity, diabetes, depression, hearing impairment and hypertension). METHODS: Using a historic cohort design, we included 9,745 participants born between 1931-48, with a mean age of 78.2 (SD = 6.4) years at the time of cognitive testing in the HUNT4 70 + sub-study (2017-2019). Further measures were obtained through data linkage between information from Statistics Norway and the HUNT1(1984-86), and HUNT2 (1995-97) Surveys. Causal mediation analyses using an inverse odd weighting approach were conducted to decompose the total effect of the number of children (0, 1, or 4 + children vs. 2-3) on the risk of dementia at age 70 + years into direct and indirect effects with mediators assessed at a mean age of 50.7 (SD = 6.4) years. The analyses were adjusted for age, sex, marital status at age 25 years, educational status, and religion assessed during HUNT3 (2006-2008). RESULTS: Overall, 15.7% were diagnosed with dementia. The proportions with dementia by the number of children were 22.3% among those with no children, 21.4% for those with one child, 13% for those with 2-3 children (specifically, 12.6% for those with 2 children and 13.4% for those with 3 children), and 19.9% for those with 4 + children. Compared to the reference group of individuals with 2-3 children, the dementia risk was higher among the groups with no children (relative risk (RR): 1.30, 95% confidence interval (CI) (1.12, 1.51)), those with one child (RR: 1.30, 95% CI (1.14, 1.47)) and those with 4 + children (RR: 1.12, 95% CI (1.01, 1.24)). The elevated risks of dementia were not mediated by the socioeconomic, psychosocial, lifestyle, or chronic diseases related factors that we tested. Sex-stratified analysis showed higher dementia risk for men without children and women with one or 4 + children compared to those with 2-3 children, with similar patterns across sexes. None of the mediators contributed to mediation in either group. None of the mediators appeared to contribute through mediation in either group. CONCLUSIONS: Our findings suggest that the number of children-specifically being childless, having one child, or having four or more children-may influence the risk of dementia. These relationships were not mediated by psychosocial, lifestyle, and socioeconomic factors, or markers of chronic diseases in adulthood considered in this study.

• MeSH
• analýza mediace * MeSH
• charakteristiky rodiny MeSH
• demence * epidemiologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• registrace * statistika a číselné údaje   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• socioekonomické faktory MeSH
• životní styl MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Norsko MeSH

The vertebrate visual cycle hinges on enzymatically converting all-trans-retinol (at-ROL) into 11-cis-retinal (11c-RAL), the chromophore that binds to opsins in photoreceptors, forming light-responsive pigments. When struck by a photon, these pigments activate the phototransduction pathway and initiate the process of vision. The enzymatic isomerization of at-ROL, crucial for restoring the visual pigments and preparing them to receive new light stimuli, relies on various enzymes found in both the photoreceptors and retinal pigment epithelium cells. To function effectively, retinoids must shuttle between these two cell types. Retinol-binding protein 3 (RBP3), located in the interphotoreceptor matrix, probably plays a pivotal role in this transport mechanism. Comprised of four retinoid-binding modules, RBP3 also binds fatty acids, potentially aiding retinal function by facilitating the loading and unloading of different retinoids at specific cell types thereby directing the cycle. In this study, we present a 3.67 Å cryoEM structure of porcine RBP3, along with molecular docking analysis and corroborative in-solution small-angle X-ray scattering data for titration of RBP3 with relevant ligands, that also give insights on RBP3 conformational adaptability.

• MeSH
• difrakce rentgenového záření MeSH
• elektronová kryomikroskopie metody   MeSH
• konformace proteinů MeSH
• maloúhlový rozptyl * MeSH
• molekulární modely MeSH
• oční proteiny MeSH
• prasata MeSH
• proteiny vázající retinol * chemie   metabolismus   MeSH
• simulace molekulového dockingu MeSH
• vazba proteinů MeSH
• vitamin A metabolismus   chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Systematic review and meta-analysis on laboratory studies aimed to answer whether there is a difference in fracture resistance and fracture mode of structurally compromised teeth restored with direct composite restorations reinforced with short glass-fiber or bidirectional polyethylene fiber substructure, and between the two different fiber-reinforcement types. METHODS: An electronic literature search was conducted in Medline, Scopus, Web of Science, Lilacs, Google Scholar, Cochrane Library, and University Library databases. The last search was conducted on 16 November 2023. Only studies looking at Ribbond-reinforced restorations and/ or the use of EverX Posterior within restorations were included. Data were categorized and analyzed based on specific outcome measures including fracture resistance and fracture mode. Data from individual studies were divided into premolars and molars for each material category and then collated to compare the mean differences in fracture resistance between control groups (composite restorations) and intervention groups (fiber-reinforced composite restorations). RESULTS: From the initial 1266 articles identified, 23 laboratory-based studies were included for quantitative analysis. Twenty articles had an overall low risk of bias and 3 had an overall unclear risk of bias. The pooled estimate of the effect favored the intervention groups as having statistically significant higher fracture resistance when compared to control groups. CONCLUSIONS: Both fiber types improve fracture resistance and the fracture mode of structurally compromised teeth is equally efficient. Application technique deserves attention. Ribbond could be placed in a single layer at the cavity floor, whereas EverX Posterior should replace missing dentin in an anatomically shaped way.

• MeSH
• fraktury zubů * prevence a kontrola   MeSH
• lidé MeSH
• polyethyleny MeSH
• sklo chemie   MeSH
• složené pryskyřice * terapeutické užití   chemie   MeSH
• trvalá zubní náhrada * metody   MeSH
• zubní materiály chemie   MeSH
• zuby-sanace - selhání MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH