INTRODUCTION: The exposures to hazardous antineoplastic drugs (AD) represent serious risks for health care personnel but the exposure limits are not commonly established because of the no-threshold effects (genotoxic action, carcinogenicity) of many ADs. In this study, we discussed and derived practically applicable technical guidance values (TGV) suitable for management of AD risks. METHODS: The long-term monitoring of surface contamination by eight ADs was performed in pharmacies and hospitals in the Czech Republic and Slovak Republic in 2008-2021; in total 2,223 unique samples were collected repeatedly in 48 facilities. AD contamination was studied by LC-MS/MS for cyclophosphamide, ifosfamide, methotrexate, irinotecan, paclitaxel, 5-fluorouracil and gemcitabine and by ICP-MS for total Pt as a marker of platinum-based ADs. RESULTS: The study highlighted importance of exposure biomarkers like 5-fluorouracil and especially carcinogenic and persistent cyclophosphamide, which should be by default included in monitoring along with other ADs. Highly contaminated spots like interiors of laminar biological safety cabinets represent a specific issue, where monitoring of contamination does not bring much added value, and prevention of staff and separated cleaning procedures should be priority. Rooms and surfaces in health care facilities that should be virtually free of ADs (e.g., offices, kitchenettes, daily rooms) were contaminated with lower frequency and concentrations but any contamination in these areas should be carefully examined. DISCUSSION AND CONCLUSIONS: For all other working places, i.e., majority of areas in pharmacies and hospitals, where ADs are being prepared, packaged, stored, transported, or administered to patients, the study proposes a generic TGV of 100 pg/cm2. The analysis of long-term monitoring data of multiple ADs showed that the exceedance of one TGV can serve as an indicator and trigger for improvement of working practices contributing thus to minimizing of unintended exposures and creating a safe work environment.
- MeSH
- antitumorózní látky * MeSH
- chromatografie kapalinová MeSH
- cyklofosfamid analýza MeSH
- fluorouracil analýza MeSH
- lékárny * MeSH
- lidé MeSH
- nemocnice MeSH
- pracovní expozice * analýza MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
AIMS: Impaired lung function has been strongly associated with cardiovascular disease (CVD) events. We aimed to assess the additive prognostic value of spirometry indices to the risk estimation of CVD events in Eastern European populations in this study. METHODS: We randomly selected 14,061 individuals with a mean age of 59 ± 7.3 years without a previous history of cardiovascular and pulmonary diseases from population registers in the Czechia, Poland, and Lithuania. Predictive values of standardised Z-scores of forced expiratory volume measured in 1 s (FEV1), forced vital capacity (FVC), and FEV1 divided by height cubed (FEV1/ht3) were tested. Cox proportional hazards models were used to estimate hazard ratios (HRs) of CVD events of various spirometry indices over the Framingham Risk Score (FRS) model. The model performance was evaluated using Harrell's C-statistics, likelihood ratio tests, and Bayesian information criterion. RESULTS: All spirometry indices had a strong linear relation with the incidence of CVD events (HR ranged from 1.10 to 1.12 between indices). The model stratified by FEV1/ht3 tertiles had a stronger link with CVD events than FEV1 and FVC. The risk of CVD event for the lowest vs. highest FEV1/ht3 tertile among people with low FRS was higher (HR: 2.35; 95% confidence interval: 1.96-2.81) than among those with high FRS. The addition of spirometry indices showed a small but statistically significant improvement of the FRS model. CONCLUSIONS: The addition of spirometry indices might improve the prediction of incident CVD events particularly in the low-risk group. FEV1/ht3 is a more sensitive predictor compared to other spirometry indices.
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The proportion of older adults within society is sharply increasing and a better understanding of how we age starts to be critical. However, given the paucity of longitudinal studies with both neuroimaging and epigenetic data, it remains largely unknown whether the speed of the epigenetic clock changes over the life course and whether any such changes are proportional to changes in brain aging and cognitive skills. To fill these knowledge gaps, we conducted a longitudinal study of a prenatal birth cohort, studied epigenetic aging across adolescence and young adulthood, and evaluated its relationship with brain aging and cognitive outcomes. METHODS: DNA methylation was assessed using the Illumina EPIC Platform in adolescence, early and late 20 s, DNA methylation age was estimated using Horvath's epigenetic clock, and epigenetic age gap (EpiAGE) was calculated as DNA methylation age residualized for batch, chronological age and the proportion of epithelial cells. Structural magnetic resonance imaging (MRI) was acquired in both the early 20 s and late 20 s using the same 3T Prisma MRI scanner and brain age was calculated using the Neuroanatomical Age Prediction using R (NAPR) platform. Cognitive skills were assessed using the Wechsler Adult Intelligence Scale (WAIS) in the late 20 s. RESULTS: The EpiAGE in adolescence, the early 20 s, and the late 20 s were positively correlated (r = 0.34-0.47), suggesting that EpiAGE is a relatively stable characteristic of an individual. Further, a faster pace of aging between the measurements was positively correlated with EpiAGE at the end of the period (r = 0.48-0.77) but negatively correlated with EpiAGE at the earlier time point (r = -0.42 to -0.55), suggesting a compensatory mechanism where late matures might be catching up with the early matures. Finally, higher positive EpiAGE showed small (Adj R2 = 0.03) but significant relationships with a higher positive brain age gap in all participants and lower full-scale IQ in young adult women in the late 20 s. DISCUSSION: We conclude that the EpiAGE is a relatively stable characteristic of an individual across adolescence and early adulthood, but that it shows only a small relationship with accelerated brain aging and a women-specific relationship with worse performance IQ.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The impact of the urban environment on human health is a contemporary subject of environmental research. Air pollution is often considered a leading environmental driver. However, a plethora of other factors within the urban exposome may be involved. At the same time, the resolution of spatial data is also an important facet to consider. Generally, systematic tools for accurate health risk assessment in the urban environment are missing or are not implemented. METHODS: The long-term impact of air quality (PM10, PM2.5, NO2, benzene, and SO2) on respiratory and cardiovascular health was assessed with a log-linear model. We used the most accurate health data in high city scale spatial resolution over the period 2010 to 2018. Selected external exposome parameters were also included in the analysis. RESULTS: Statistically significant associations between air pollution and the health of the urban population were found. The strongest association was between benzene and the incidence of bronchitis in the adult population [RR 1.552 95% CI (1.415-1.704) per 0.5 μg/m3 change in benzene concentration]. A similar relation was observed between NO2 and the same health condition [RR 1.483 95% CI (1.227-1.792) per 8.9 μg/m3 of change in NO2]. Other weaker associations were also found between asthma in children and PMs, NO2, or benzene. Cardiovascular-related hospitalizations in the general population were linked with NO2 [RR 1.218 95% CI (1.119-1.325) per 9.7 μg/m3 change in NO2]. The remaining pollutants were slightly less but still significantly associated with cardiovascular-related hospitalizations. CONCLUSION: Our findings are mostly highly statistically significant (p ≤ 0.001) and are in line with current literature on the adverse effects of air pollution on the human population. The results highlight the need for continual improvements in air quality. We propose the implementation of this approach as a systematic tool for the investigation of possible health risks over a long period of time. However, further research involving other variables is an essential step toward understanding the complex urban exposome and its implications for human health. An increase in data spatial resolution is especially important in this respect as well as for improving city health risk management.
- MeSH
- benzen analýza MeSH
- dítě MeSH
- dospělí MeSH
- látky znečišťující vzduch * škodlivé účinky analýza MeSH
- lidé MeSH
- oxid dusičitý analýza MeSH
- velkoměsta epidemiologie MeSH
- znečištění ovzduší * škodlivé účinky analýza MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- velkoměsta epidemiologie MeSH
Objectives: Osteocalcin is a protein secreted by osteoblasts with a versatile endocrine role. Several domains in which it plays a role-stress response, monoamine synthesis, and cognitive functioning-are implicated also in the pathophysiology of major depressive disorder. In search of possible objective biomarkers of depression, the aim of the study was to assess the relationship between osteocalcin and depressive symptoms during the treatment of depressive episode. Methods: The study included female inpatients with at least moderate depressive episode. In these patients, depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), and osteocalcin levels were assessed before the stabilization of antidepressive treatment and after 6 weeks. Relationships between osteocalcin levels and symptoms were analyzed with mixed-effect and linear models, taking into account age, menopausal status, and body mass index. Results: In 11 out of 13 enrolled inpatients, osteocalcin levels decreased during the first 6 weeks of treatment; this decrease was significant according to the mixed-effects model (t = -2.345, p = 0.019). According to the linear model, this decrease was significantly associated with reduction in depressive symptom severity (t = 2.673, p = 0.028). Osteocalcin was not associated with initial depressive symptom severity, and initial osteocalcin levels did not predict response to treatment. Limitations of the study include low sample size and inclusion of both pre- and postmenopausal women of various ages. Conclusions: This preliminary study suggests that osteocalcin may be a candidate biomarker of antidepressive treatment response and that this topic warrants further investigation.
- Publikační typ
- časopisecké články MeSH
To this date, there are no recommendations for personalized stress ulcer prophylaxis (SUP) in critical care that would take the patient's individual genetic predispositions into account. Of drugs used for this purpose, proton pump inhibitors (PPIs) are the first-choice drugs in intensive care unit patients. The degradation of proton pump inhibitors is mediated by cytochrome P450 (CYP) enzymes; in particular, CYP2C19 and, to a lesser extent, CYP3A4 are involved. Expression and metabolic activity of, namely in, CYP2C19 is significantly affected by single nucleotide polymorphisms, the drug metabolization rate varies greatly from ultrarapid to poor and likely influences the optimal dosage. As these CYP2C19 predictive phenotypes via CYP2C19 haplogenotypes (rs12248560/rs4244285) can be relatively easily determined using the current standard equipment of hospital laboratories, we prepared a set of recommendations for personalized PPI-based stress ulcer prophylaxis taking into account the patient's CYP2C19 predictive phenotype determined in this way. These recommendations are valid, in particular, for European, American and African populations, because these populations have the high representations of the CYP2C19*17 allele associated with the overexpression of the CYP2C19 gene and ultrarapid degradation of PPIs. We propose the CYP2C19 gene profiling as a tool for personalized SUP with PPI in critically ill patients.
- Publikační typ
- časopisecké články MeSH
Copper oxide nanoparticles (CuO NPs) are increasingly used in various industry sectors. Moreover, medical application of CuO NPs as antimicrobials also contributes to human exposure. Their toxicity, including toxicity to the immune system and blood, raises concerns, while information on their immunotoxicity is still very limited. The aim of our work was to evaluate the effects of CuO NPs (number concentration 1.40×106 particles/cm3, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 μg CuO/m3 continuously for 6 weeks. After six weeks of CuO NP inhalation, the content of copper in lungs and liver was significantly increased, while in kidneys, spleen, brain, and blood it was similar in exposed and control mice. Inhalation of CuO NPs caused a significant increase in proliferative response of T-lymphocytes after mitogenic stimulation and basal proliferative activity of splenocytes. CuO NPs significantly induced the production of IL-12p70, Th1-cytokine IFN-γ and Th2-cytokines IL-4, IL-5. Levels of TNF-α and IL-6 remained unchanged. Immune assays showed significantly suppressed phagocytic activity of granulocytes and slightly decreased respiratory burst. No significant differences in phagocytosis of monocytes were recorded. The percentage of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD19+ cell subsets in spleen, thymus, and lymph nodes did not differ between exposed and control animals. No changes in hematological parameters were found between the CuO NP exposed and control groups. The overall antioxidant protection status of the organism was expressed by evaluation of GSH and GSSG concentrations in blood samples. The experimental group exposed to CuO NPs showed a significant decrease in GSH concentration in comparison to the control group. In summary, our results indicate that sub-chronic inhalation of CuO NPs can cause undesired modulation of the immune response. Stimulation of adaptive immunity was indicated by activation of proliferation and secretion functions of lymphocytes. CuO NPs elicited pro-activation state of Th1 and Th2 lymphocytes in exposed mice. Innate immunity was affected by impaired phagocytic activity of granulocytes. Reduced glutathione was significantly decreased in mice exposed to CuO NPs.
BACKGROUND: Biological aging and particularly the deviations between biological and chronological age are better predictors of health than chronological age alone. However, the predictors of accelerated biological aging are not very well understood. The aim was to determine the role of birth outcomes, time of puberty onset, body mass index (BMI), and body fat in accelerated biological aging in the third decade of life. METHODS: We have conducted a second follow-up of the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ) prenatal birth cohort in young adulthood (52% male; age 28-30; n = 262) to determine the role of birth outcomes, pubertal timing, BMI, and body fat on biological aging. Birth outcomes included birth weight, length, and gestational age at birth. Pubertal timing was determined by the presence of secondary sexual characteristics at the age of 11 and the age of first menarche in women. Biological age was estimated using the Klemera-Doubal Method (KDM), which applies 9-biomarker algorithm including forced expiratory volume in one second (FEV1), systolic blood pressure, glycated hemoglobin, total cholesterol, C-reactive protein, creatinine, urea nitrogen, albumin, and alkaline phosphatase. Accelerated/decelerated aging was determined as the difference between biological and chronological age (BioAGE). RESULTS: The deviations between biological and chronological age in young adulthood ranged from -2.84 to 4.39 years. Accelerated biological aging was predicted by higher BMI [in both early (R2adj = 0.05) and late 20s (R2adj = 0.22)], subcutaneous (R2adj = 0.21) and visceral fat (R2adj = 0.25), puberty onset (η p2 = 0.07), birth length (R2adj = 0.03), and the increase of BMI over the 5-year period between the two follow-ups in young adulthood (R2adj = 0.09). Single hierarchical model revealed that shorter birth length, early puberty onset, and greater levels of visceral fat were the main predictors, together explaining 21% of variance in accelerated biological aging. CONCLUSION: Our findings provide comprehensive support of the Life History Theory, suggesting that early life adversity might trigger accelerated aging, which leads to earlier onset of puberty but decreasing fitness in adulthood, reflected by more visceral fat and higher BMI. Our findings also suggest that reduction of BMI in young adulthood slows down biological aging.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Biological aging and particularly the deviations between biological and chronological age are better predictors of health than chronological age alone. However, the predictors of accelerated biological aging are not very well understood. The aim was to determine the role of birth outcomes, time of puberty onset, body mass index (BMI), and body fat in accelerated biological aging in the third decade of life. METHODS: We have conducted a second follow-up of the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ) prenatal birth cohort in young adulthood (52% male; age 28-30; n = 262) to determine the role of birth outcomes, pubertal timing, BMI, and body fat on biological aging. Birth outcomes included birth weight, length, and gestational age at birth. Pubertal timing was determined by the presence of secondary sexual characteristics at the age of 11 and the age of first menarche in women. Biological age was estimated using the Klemera-Doubal Method (KDM), which applies 9-biomarker algorithm including forced expiratory volume in one second (FEV1), systolic blood pressure, glycated hemoglobin, total cholesterol, C-reactive protein, creatinine, urea nitrogen, albumin, and alkaline phosphatase. Accelerated/decelerated aging was determined as the difference between biological and chronological age (BioAGE). RESULTS: The deviations between biological and chronological age in young adulthood ranged from -2.84 to 4.39 years. Accelerated biological aging was predicted by higher BMI [in both early (R2adj = 0.05) and late 20s (R2adj = 0.22)], subcutaneous (R2adj = 0.21) and visceral fat (R2adj = 0.25), puberty onset (η p2 = 0.07), birth length (R2adj = 0.03), and the increase of BMI over the 5-year period between the two follow-ups in young adulthood (R2adj = 0.09). Single hierarchical model revealed that shorter birth length, early puberty onset, and greater levels of visceral fat were the main predictors, together explaining 21% of variance in accelerated biological aging. CONCLUSION: Our findings provide comprehensive support of the Life History Theory, suggesting that early life adversity might trigger accelerated aging, which leads to earlier onset of puberty but decreasing fitness in adulthood, reflected by more visceral fat and higher BMI. Our findings also suggest that reduction of BMI in young adulthood slows down biological aging.
- Publikační typ
- časopisecké články MeSH
National screening programs use dried blood specimens to detect metabolic disorders or aberrant protein functions that are not clinically evident in the neonatal period. Similarly, gut microbiota metabolites and immunological acute-phase proteins may reveal latent immune aberrations. Microbial metabolites interact with xenobiotic receptors (i.e., aryl hydrocarbon and pregnane-X) to maintain gastrointestinal tissue health, supported by acute-phase proteins, functioning as sensors of microbial immunomodulation and homeostasis. The delivery (vaginal or cesarean section) shapes the microbial colonization, which substantially modulates both the immune system's response and mucosal homeostasis. This study profiled microbial metabolites of the kynurenine and tryptophan pathway and acute-phase proteins in 134 neonatal dried blood specimens. We newly established neonatal blood levels of microbial xenobiotic receptors ligands (i.e., indole-3-aldehyde, indole-3-butyric acid, and indole-3-acetamide) on the second day of life. Furthermore, we observed diverse microbial metabolic profiles in neonates born vaginally and via cesarean section, potentially due to microbial immunomodulatory influence. In summary, these findings suggest the supportive role of human gut microbiota in developing and maintaining immune system homeostasis.
- Publikační typ
- časopisecké články MeSH
