Acute coronary syndrome (ACS), specifically ST-segment elevation myocardial infarction is a major cause of morbidity and mortality throughout Europe. Diagnosis in the acute setting is mainly based on ...clinical symptoms and physician's interpretation of an electrocardiogram (ECG), which may be subject to errors. ST-segment elevation is the leading criteria to activate urgent reperfusion therapy, but a clear ST-elevation pattern might not be present in patients with coronary occlusion and ST-segment elevation might be seen in patients with normal coronary arteries.
The ASSIST project is a retrospective observational study aiming to improve the ECG-assisted assessment of ACS patients in the acute setting by incorporating an artificial intelligence platform, Willem™ to analyze 12‑lead ECGs. Our aim is to improve diagnostic accuracy and reduce treatment delays. ECG and clinical data collected during this study will enable the optimization and validation of Willem™. A retrospective multicenter study will collect ECG, clinical, and coronary angiography data from 10,309 patients. The primary outcome is the performance of this tool in the correct identification of acute myocardial infarction with coronary artery occlusion. Model performance will be evaluated internally with patients recruited in this retrospective study while external validation will be performed in a second stage.
ASSIST will provide key data to optimize Willem™ platform to detect myocardial infarction based on ECG-assessment alone. Our hypothesis is that such a diagnostic approach may reduce time delays, enhance diagnostic accuracy, and improve clinical outcomes.
•ECG is the first step to diagnose myocardial infarction in emergency setting.•ST elevation activates emergent reperfusion but might be absent in coronary artery occlusion.•AI-based ECG interpretation may reduce time delays and enhance diagnostic•accuracy.•The ASSIST project aims at providing key data to optimize such an AI platform.
Russian sturgeon (Acipenser gueldenstaedtii) has been successfully farmed in Uruguay for the past ten years. However, during the Uruguayan summer fish endure high water temperatures and increased ...bacterial infections that threaten aquaculture. Our understanding of sturgeon's immune system and its interplay with environmental factors like temperature is almost unknown. This study analysed the way in which seasonal variations affect enzymatic blood components of Russian sturgeon's innate defences, including the serum alternative complement pathway (ACP), ceruloplasmin (Cp) and lysozyme activities. Results showed that summertime conditions in the farm altered these defences in different ways, inducing a significant decrease in ACP and Cp, and an increase in lysozyme. In addition, serum levels of total protein and cortisol decreased in summer, suggesting a chronic stress response was induced in parallel. Subsequently, we analysed whether the increase in water river temperature during summer could account for the observed results. To that end, we acclimated juvenile sturgeons to mild (18 °C) or warm (24 °C) temperatures for 37 days. Like in summer, sturgeons exposed to 24 °C showed lower levels of serum ACP, Cp and total proteins, together with a progressive decrease in body weight and increased fish mortality. Administration of an immunostimulant containing Se and Zn slightly reverted the temperature-induced effects on sturgeon's defences. Altogether, our study provides novel data on various physiological parameters of the Russian sturgeon and highlights the impact warm temperature has on stress and innate immunity in this chondrostean fish.
•We describe novel data on Russian sturgeon's innate defences and stress response.•Uruguayan summer conditions weaken sturgeon's innate soluble components.•Weakened defences correlated with a chronic stress response.•Long-term exposure to 24 °C reproduces summer-induced alterations.
Several guidelines recommend using the Clinical Frailty Scale (CFS) for triage of critically ill coronavirus disease 2019 (COVID-19) patients. This study evaluates the impact of CFS on intensive care ...unit (ICU) admission rate and hospital and ICU mortality rates in hospitalized dialysis patients with COVID-19.
We analysed data of dialysis patients diagnosed with COVID-19 from the European Renal Association COVID-19 Database. The primary outcome was ICU admission rate and secondary outcomes were hospital and ICU mortality until 3 months after COVID-19 diagnosis. Cox regression analyses were performed to assess associations between CFS and outcomes.
A total of 1501 dialysis patients were hospitalized due to COVID-19, of whom 219 (15%) were admitted to an ICU. The ICU admission rate was lowest (5%) in patients >75 years of age with a CFS of 7-9 and highest (27%) in patients 65-75 years of age with a CFS of 5. A CFS of 7-9 was associated with a lower ICU admission rate than a CFS of 1-3 relative risk 0.49 (95% confidence interval 0.27-0.87). Overall, mortality at 3 months was 34% in hospitalized patients, 65% in ICU-admitted patients and highest in patients >75 years of age with a CFS of 7-9 (69%). Only 9% of patients with a CFS ≥6 survived after ICU admission. After adjustment for age and sex, each CFS category ≥4 was associated with higher hospital and ICU mortality compared with a CFS of 1-3.
Frail dialysis patients with COVID-19 were less frequently admitted to the ICU. Large differences in mortality rates between fit and frail patients suggest that the CFS may be a useful complementary triage tool for ICU admission in dialysis patients with COVID-19.
Despite recent advances with monoclonal antibody therapy, chronic lymphocytic leukemia (CLL) remains incurable. Natural killer (NK) cells are potent antitumoral effectors, particularly against ...hematological malignancies. Defective recognition of B-CLL leukemic cells by NK cells has been previously described. Here, we deciphered the mechanisms that hamper NK cell-mediated clearance of B-CLL and evaluated the potential of NK cells as therapeutic tools for treatment of CLL. First of all, leukemic B cells resemble to normal B cells with a weak expression of ligands for NK receptors. Conversely, NK cells from B-CLL patients were functionally and phenotypically competent, despite a decrease of expression of the activating receptor NKp30. Consequently, resting allogeneic NK cells were unable to kill leukemic B cells in vitro. These data suggest that patients’ NK cells cannot initiate a proper immune reaction due to a lack of leukemic cell recognition. We next set up a xenotransplantation mouse model to study NK-CLL cell interactions. Together with our in vitro studies, in vivo data revealed that activation of NK cells is required in order to control B-CLL and that activated NK cells synergize to enhance rituximab effect on tumor load. This study points out the requirements for immune system manipulation for treatment of B-CLL in combination with monoclonal antibody therapy.
This study aimed to estimate airborne nicotine concentrations and nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) in settled dust from private cars in Spain and the UK.
We measured ...vapor-phase nicotine concentrations in a convenience sample of 45 private cars from Spain (N = 30) and the UK (N = 15) in 2017–2018. We recruited non-smoking drivers (n = 20), smoking drivers who do not smoke inside the car (n = 15), and smoking drivers who smoke inside (n = 10). Nicotine, cotinine, and three TSNAs (NNK, NNN, NNA) were also measured in settled dust in a random subsample (n = 20). We computed medians and interquartile ranges (IQR) of secondhand smoke (SHS) and thirdhand smoke (THS) compounds according to the drivers’ profile.
24-h samples yielded median airborne nicotine concentrations below the limit of quantification (LOQ) (IQR: <LOQ - <LOQ) in non-smokers’ cars, 0.23 μg/m3 (IQR:0.18–0.45) in cars of smokers not smoking inside, and 3.53 μg/m3, (IQR:1.74–6.38) in cars of smokers smoking inside (p < 0.001). Nicotine concentrations measured only while travelling increased to 21.44 μg/m3 (IQR:6.60–86.15) in cars of smokers smoking inside. THS concentrations were higher in all cars of smokers, and specially in cars of drivers smoking inside (nicotine: 38.9 μg/g (IQR:19.3–105.7); NNK: 28.5 ng/g (IQR:26.6–70.2); NNN: 23.7 ng/g (IQR:14.3–55.3)), THS concentrations being up to six times those in non-smokers’ cars.
All cars of smokers had measurable SHS and THS pollution, the exposure levels markedly higher in vehicles of drivers where smoking took place. Our results evidence the need for policies to prohibit smoking in vehicles, but also urge for more comprehensive strategies aiming towards the elimination of tobacco consumption.
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•We monitored SHS and THS exposure in cars in two European countries.•SHS concentrations in cars of smokers who smoke inside were extremely high.•In cars of smokers who smoke inside, median airborne nicotine measured only while travelling was 21.44 μg/m3.•THS concentrations in cars of smokers who smoke inside were up to six times those in non-smokers’ cars.•Smoking should be banned in vehicles to protect effectively from tobacco smoke pollution exposure.
The nitrososulfonate ion (N(O)SO3−) has been proposed to be formed in stomach by the reaction of nitrite and sulfite ions. Nevertheless, very little is known about the chemistry of N(O)SO3−, which is ...unstable and generates reactive species. Aiming to provide a better knowledge on the chemistry and biological relevance of the N(O)SO3−, we synthesized a nitrosylsulphito complex trans-Ru(NH3)4(isn)(N(O)SO3)+ (isn=isonicotinamide) as a stable and delivery agent of N(O)SO3− via photoactivation. This complex was characterized by spectroscopic means, single-crystal X-ray diffraction, and supported by DFT calculations. Electronic and NMR spectroscopy revealed that trans-Ru(NH3)4(isn)(N(O)SO3)+ is stable in phosphate buffer with a k = 3.0×10-5s-1 (t1/2~385 min, at 25 °C) for isn labilization. At acidic conditions (1.0 M HTFA) trans-Ru(NH3)4(isn)(N(O)SO3)+ is found to be converted back to the synthetic precursor trans-Ru(NH3)4(isn)(NO)3+. This process is proposed to be related to the protonation of the SO3 fragment in the coordinated N(O)SO3 ligand (pKa~5) favoring the S–N bond cleavage. An intense absorption band at 363 nm (ε=6.0×103M−1cm−1) observed for trans-Ru(NH3)4(isn)(N(O)SO3)+ was assigned by DFT as a metal-to-ligand charge transfer (Ru→N(O)SO3) transition. Upon photolysis at 355 nm in phosphate buffer, trans-Ru(NH3)4(isn)(N(O)SO3)+ releases NO and SO3●−, by a probable mechanism in which N(O)SO3− ligand is photoreleased and further dissociates into NO• and SO3●− species. SO3●– is one of the few sulfur radical species found in cells, which despite its relative low reduction potential (Eº~0.63 V) may promote oxidative damage by acting as a prooxidant and precursor of sulfate radical (SO4●–), a strong oxidant (Eº ~ 2.5 V vs. NHE). Thus, the newly synthesized nitrosylsulphito complex seems to be a valuable source of N(O)SO3−, nitric oxide and sulfite radical (SO3●–).
Summary It is presently unclear whether there is a significant association between thyroid function and cognitive decline in euthyroid elderly. This case–control study aimed to examine serum thyroid ...stimulating hormone (TSH), total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine in relation to cognitive decline over a 3-year period in a subsample of 62 participants (31 pairs) aged 67 years and over at baseline from the NuAge study (Quebec longitudinal study). They were matched for age, sex and global cognition. In conditional regression logistic models, there was no significant association between any thyroid function indices and the 3-year risk of cognitive decline as measured with the Modified Mini-Mental State Examination (3MS). TSH and thyroid hormones do not appear to be associated with cognitive decline in euthyroid older persons. These findings need confirmation given the small number of pairs of subjects.
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