BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis, when 75% of anticipated participants had completed follow up, the data and safety monitoring board recommended to terminate the trial, and upon unblinding, the operations committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group, and 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5% [95% CI, -0.9 to 0.03]; P=0.07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3% [95% CI, 5.2-11.5]; P=0.007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared with the intravenous group was 8.2% (95% CI, 3.4-12.9). CONCLUSIONS: Among patients undergoing cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared with intravenous tranexamic acid. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03954314.

• MeSH
• antifibrinolytika * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• aplikace lokální * MeSH
• dvojitá slepá metoda MeSH
• intravenózní podání * MeSH
• kardiochirurgické výkony * škodlivé účinky   MeSH
• krvácení při operaci prevence a kontrola   MeSH
• kyselina tranexamová * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• výsledek terapie MeSH
• záchvaty prevence a kontrola   etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

We present the temporal trends and spatial changes of deposition of sulphur and nitrogen in Czech forests based on records from long-term monitoring. A statistically significant trend for sulphur was detected at most of the sites measuring for wet, dry, and total deposition fluxes and at many of these the trend was also present for the period after 2000. The spatial pattern of the changes in sulphur deposition flux between 1995 and 2011 shows the decrease over the entire forested area in a wide range of 18.1-0.2 g m(-2) year(-1) with the most pronounced improvement in formerly most impacted regions. Nitrogen still represents a considerable stress in many areas. The value of nitrogen deposition flux of 1 g m(-2) year(-1) is exceeded over a significant portion of the country. On an equivalent basis, the ion ratios of NO3(-)/SO4(2-) and NH4(+)/SO4(2-) in precipitation show significantly increasing trends in time similarly to those of pH.

• MeSH
• dusík analýza   MeSH
• látky znečišťující vzduch analýza   MeSH
• monitorování životního prostředí * MeSH
• síra analýza   MeSH
• stromy * MeSH
• znečištění ovzduší statistika a číselné údaje   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

A number of studies have focused on urban trees to understand their mitigation capacity of air pollution. In this study particulate matter (PM) deposition on Quercus ilex leaves was quantitatively analyzed in four districts of the City of Terni (Italy) for three periods of the year. Fine (between 0.2 and 2.5 μm) and Large (between 2.5 and 10 μm) PM fractions were analyzed. Mean PM deposition value on Quercus ilex leaves was 20.6 μg cm(-2). Variations in PM deposition correlated with distance to main roads and downwind position relatively to industrial area. Epicuticular waxes were measured and related to accumulated PM. For Fine PM deposited in waxes we observed a higher value (40% of total Fine PM) than Large PM (4% of total Large PM). Results from this study allow to increase our understanding about air pollution interactions with urban vegetation and could be hopefully taken into account when guidelines for local urban green management are realized.

• MeSH
• dub (rod) chemie   MeSH
• látky znečišťující vzduch analýza   MeSH
• listy rostlin chemie   MeSH
• monitorování životního prostředí metody   MeSH
• pevné částice analýza   MeSH
• stromy MeSH
• velkoměsta MeSH
• znečištění ovzduší statistika a číselné údaje   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Itálie MeSH
• velkoměsta MeSH

The quantification of atmospheric deposition flux is essential for assessment of its impact on ecosystems. We present an advanced approach for the estimation of the spatial pattern of atmospheric nitrogen deposition flux over the Czech forests, collating all available measured data and model results. The aim of the presented study is to provide an improved, more complete, more reliable and more realistic estimate of the spatial pattern of nitrogen deposition flux over one country. This has so far usually been based on measurements of ambient NOx concentrations as dry deposition proxy, and [Formula: see text] and [Formula: see text] in precipitation as wet deposition proxy. For estimation of unmeasured species contributing to dry deposition, we used the CAMx Eulerian photochemical dispersion model, coupled with the Aladin regional numeric weather prediction model. The contribution of fog and dissolved organic nitrogen was estimated using a geostatistical data driven model. We prepared individual maps for particular components applying the most relevant approach and then merged all layers to obtain a final map representing the best estimate of nitrogen deposition over the Czech Republic. Final maps accounting for unmeasured species clearly indicate that the approach used so far may result in a substantial underestimation of nitrogen deposition flux. Our results showed that nitrogen deposition over the Czech forested area in 2008 was well above 2 g N m(-2) yr(-1), with almost 70% of forested area receiving 3-4 g N m(-2) yr(-1). NH3 and gaseous HNO3, contributing about 80%, dominated the dry nitrogen deposition. Estimating the unmeasured nitrogen species by modeled values provides realistic approximations of total nitrogen deposition that also result in more realistic spatial patterns that could be used as input for further studies of likely nitrogen impacts on ecosystems.

• MeSH
• atmosféra chemie   MeSH
• dusík analýza   MeSH
• látky znečišťující vzduch analýza   MeSH
• lesy * MeSH
• monitorování životního prostředí metody   MeSH
• počasí MeSH
• statistické modely MeSH
• stromy MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are ubiquitous and toxic contaminants. Their atmospheric deposition fluxes on the regional scale were quantified based on simultaneous sampling during 1 to 5 years at 1 to 6 background/rural sites in the Czech Republic and Austria. The samples were extracted and analysed by means of gas chromatography coupled to mass spectrometry. For all seasons and sites, total deposition fluxes for Σ15PAHs ranged 23-1100 ng m-2 d-1, while those for Σ6PCBs and Σ12OCPs ranged 64-4400 and 410-7800 pg m-2 d-1, respectively. Fluoranthene and pyrene were the main contributors to the PAH deposition fluxes, accounting on average for 19% each, while deposition fluxes of PCBs and OCPs were dominated by PCB153 (26%) and γ-hexachlorobenzene (30%), respectively. The highest deposition flux of Σ15PAHs was generally found in spring, while no seasonality was found for PCB deposition. For deposition fluxes for Σ12OCPs, no clear spatial trend was found, confirming the perception of long-lived regional pollutants. Although most OCPs and PCBs hardly partition to the particulate phase in ambient air, on average, 42% of their deposition fluxes were found on filters, confirming the perception that particle deposition is more efficient than dry gaseous deposition. Due to methodological constraints, fluxes derived from bulk deposition samplers should be understood as lower estimates, in particular with regard to those substances which in ambient aerosols mostly partition to the particulate phase.

• MeSH
• chlorované uhlovodíky analýza   MeSH
• hexachlorbenzen analýza   MeSH
• látky znečišťující vzduch analýza   MeSH
• monitorování životního prostředí * MeSH
• pesticidy analýza   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• polychlorované bifenyly analýza   MeSH
• polycyklické aromatické uhlovodíky analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Evropa MeSH
• Rakousko MeSH

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of familial small vessel disease; no preventive or curative therapy is available. CADASIL is caused by mutations in the NOTCH3 gene, resulting in a mutated NOTCH3 receptor, with aggregation of the NOTCH3 extracellular domain (ECD) around vascular smooth muscle cells. In this study, we have developed a novel active immunization therapy specifically targeting CADASIL-like aggregated NOTCH3 ECD. Immunizing CADASIL TgN3R182C150 mice with aggregates composed of CADASIL-R133C mutated and wild-type EGF1-5 repeats for a total of 4 months resulted in a marked reduction (38-48%) in NOTCH3 deposition around brain capillaries, increased microglia activation and lowered serum levels of NOTCH3 ECD. Active immunization did not impact body weight, general behavior, the number and integrity of vascular smooth muscle cells in the retina, neuronal survival, or inflammation or the renal system, suggesting that the therapy is tolerable. This is the first therapeutic study reporting a successful reduction of NOTCH3 accumulation in a CADASIL mouse model supporting further development towards clinical application for the benefit of CADASIL patients.

• MeSH
• aktivní imunoterapie MeSH
• CADASIL * genetika   terapie   MeSH
• kapiláry metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• mozek metabolismus   MeSH
• mutace MeSH
• myši MeSH
• receptor Notch3 genetika   metabolismus   MeSH
• receptory Notch metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Inhaled corticosteroids in pressurized metered does inhalers (pMDIs) are often delivered via a large volume spacer device, but these are bulky and inconvenient. Dry powder inhalers (DPIs) provide a highly portable and convenient propellant-free alternative to pMDIs for asthma maintenance therapy However, each DPI could have unique in vivo delivery characteristcs. In order to quantify the total and regional lung deposition of budesonide (200 microg) from (a) Easyhaler, (b) Turbuhaler and (c) pMDI plus Nebuhaler 750 ml spacer, a three-way randomized cross-over study was carried out in 12 mild to moderate asthmatic patients. Deposition was quantified by the imaging technique of gamma scintigraphy Optimal inhalation techniques were used throughout. Mean (SD) whole lung deposition (% metered dose) was similar for Easyhaler [18.5 (7.8) %] and Turbuhaler [21.8 (8.2) %], but was significantly higher for pMDI plus Nebuhaler [44.1 (10.0) %, P < 0.01]. The regional distribution patterns in the lungs were predominantly central for all three devices. Nebuhaler reduced oropharyngeal deposition significantly compared with the two DPIs. Easyhaler showed comparable deposition to Turbuhaler and hence drugs delivered by Easyhaler would be expected to have a similar clinical effect to those delivered by Turbuhaler in asthma maintenance therapy.

• MeSH
• antiastmatika * aplikace a dávkování   MeSH
• aplikace inhalační MeSH
• bronchiální astma * farmakoterapie   MeSH
• budesonid * aplikace a dávkování   MeSH
• design vybavení MeSH
• dospělí MeSH
• klinické křížové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• nebulizátory a vaporizátory * normy   MeSH
• neparametrická statistika MeSH
• prášky, zásypy, pudry MeSH
• technecium diagnostické užití   MeSH
• usilovný výdechový objem MeSH
• vitální kapacita účinky léků   MeSH
• vrcholová exspirační průtoková rychlost účinky záření   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinické zkoušky MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Scots pine (Pinus sylvestris L.) is a widespread tolerant forest tree-species; however, its adaptability to environmental change differs among sites with various buffering capacity. In this study, we compared the spatial effects of aridity index (AI) and nitrogen deposition (ND) on biomass density in natural and man-made pine stands of differing soil fertility using geographically weighted multiple lag regression. Soil fertility was defined using soil series as zonal trophic (27.9%), acidic (48.2%), gleyed (15.2%) and as azonal exposed (2.5%), maple (2.4%), ash (0.8%), wet (2.1%) and peat (0.9%) under pine stands in the Czech Republic (Central Europe; 4290.5 km2; 130-1298 m a.s.l.). Annual AI and ND in every pine stand were estimated by intersection between raster and vector from 1 × 1 km grid for years 2000, 2003, 2007 and 2010 of severe non-specific forest damage spread. Biomass density was obtained from a MODIS 250 × 250 m raster using the enhanced vegetation index (EVI) for years 2000-2015, with a decrease in EVI indicating non-specific damage. Environmental change was assessed by comparing predictor values at EVI time t and t+λ. Non-specific damage was registered over 51.9% of total forest area. Less than 8.8% of damaged stands were natural and the rest (91.2%) of damaged stands were man-made. Pure pine stands were more damaged than mixed. The ND effect prevailed up to 2007, while AI dominated later. Temporal increasing ND effect under AI effectiveness led to the most significant pine stand damage in 2008 and 2014. Predictors from 2000 to 2007 afflicted 58.5% of non-specifically damaged stands at R2 0.09-0.76 (median 0.38), but from 2000 to 2010 afflicted 57.1% of the stands at R2 0.16-0.75 (median 0.40). The most damaged stands occurred on acidic sites. Mixed forest and sustainable management on natural sites seem as effective remediation reducing damage by ND.

• MeSH
• borovice lesní * MeSH
• borovice * MeSH
• dusík MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Evropa MeSH

• MeSH
• kovy analýza   MeSH
• látky znečišťující vzduch analýza   MeSH
• mechy chemie   metabolismus   MeSH

This prospective study examined the content of metals released from total joint arthroplasty into joint fluid, whole blood and periprosthetic tissues. We determined the levels of Ti, V, Nb, Co, Cr, and Mo, using inductively coupled plasma mass spectrometry, in samples from patients who underwent reoperation of total hip or knee arthroplasty. All of the patients (n = 117) included in the study had either metal on polyethylene or ceramic on polyethylene-bearing pairs. First, our results conclusively showed that the majority of released metals were deposited in periprosthetic tissues. In this context, the bloodstream turned out to be an ineffective biomarker of the effects occurring in local tissues. Second, there was a clear time-dependent nature of metallic accumulation. Based on our extensive dataset, we found significantly elevated levels of the released metals in joint fluid and periprosthetic tissues originating from loosened implants compared to stable ones, as well as recognizable differences between the groups with stable implants and aseptic loosening. Finally, it was proved that the concentrations of metals decreased dependent on the distance of the tissue from the implant. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 454-462, 2019.

• MeSH
• dospělí MeSH
• kovy farmakokinetika   MeSH
• kyčelní protézy škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada kyčelního kloubu * MeSH
• prospektivní studie MeSH
• protézy kolene škodlivé účinky   MeSH
• selhání protézy škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• synoviální tekutina metabolismus   MeSH
• totální endoprotéza kolene * 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
• práce podpořená grantem MeSH