Aims
Data on the impact of COVID‐19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking. The aim of this work was to study characteristics, ...cardiovascular outcomes and mortality in patients with confirmed COVID‐19 infection and a prior diagnosis of heart failure (HF). Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline‐directed medical therapy (GDMT) and worse outcomes during hospitalization.
Methods and results
Data for a total of 3080 consecutive patients with confirmed COVID‐19 infection and follow‐up of at least 30 days were analysed. Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs. 2.1%; P < 0.001) and had higher levels of N‐terminal pro brain natriuretic peptide. In addition, patients with previous CHF had higher mortality rates (48.7% vs. 19.0%; P < 0.001). In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF. Arrhythmias during hospital admission and CHF were the main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs. 19.7%; P < 0.001). Finally, the withdrawal of beta‐blockers, mineralocorticoid receptor antagonists and angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in‐hospital mortality.
Conclusions
Patients with COVID‐19 have a significant incidence of AHF, which is associated with very high mortality rates. Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID‐19 diagnosis. The withdrawal of GDMT was associated with higher mortality.
Heart failure in COVID‐19 patients: prevalence, incidence and prognostic implications.
The large majority of antibiotics currently used for treating infections and the antibiotic resistance genes acquired by human pathogens each have an environmental origin. Recent work indicates that ...the function of these elements in their environmental reservoirs may be very distinct from the "weapon-shield" role they play in clinical settings. Changes in natural ecosystems, including the release of large amounts of antimicrobials, might alter the population dynamics of microorganisms, including selection of resistance, with consequences for human health that are difficult to predict.
The development of transition metal catalysts capable of promoting non-natural transformations within living cells can open significant new avenues in chemical and cell biology. Unfortunately, the ...complexity of the cell makes it extremely difficult to translate standard organometallic chemistry to living environments. Therefore, progress in this field has been very slow, and many challenges, including the possibility of localizing active metal catalysts into specific subcellular sites or organelles, remain to be addressed. Herein, we report a designed ruthenium complex that accumulates preferentially inside the mitochondria of mammalian cells, while keeping its ability to react with exogenous substrates in a bioorthogonal way. Importantly, we show that the subcellular catalytic activity can be used for the confined release of fluorophores, and even allows selective functional alterations in the mitochondria by the localized transformation of inert precursors into uncouplers of the membrane potential.
The aim of virtual screening (VS) is to identify bioactive compounds through computational means, by employing knowledge about the protein target (structure-based VS) or known bioactive ligands ...(ligand-based VS). In VS, a large number of molecules are ranked according to their likelihood to be bioactive compounds, with the aim to enrich the top fraction of the resulting list (which can be tested in bioassays afterward). At its core, VS attempts to improve the odds of identifying bioactive molecules by maximizing the true positive rate, that is, by ranking the truly active molecules as high as possible (and, correspondingly, the truly inactive ones as low as possible). In choosing the right approach, the researcher is faced with many questions: where does the optimal balance between efficiency and accuracy lie when evaluating a particular algorithm; do some methods perform better than others and in what particular situations; and what do retrospective results tell us about the prospective utility of a particular method? Given the multitude of settings, parameters, and data sets the practitioner can choose from, there are many pitfalls that lurk along the way which might render VS less efficient or downright useless. This review attempts to catalogue published and unpublished problems, shortcomings, failures, and technical traps of VS methods with the aim to avoid pitfalls by making the user aware of them in the first place.
Abstract
Background
The role of vitamin D status in COVID-19 patients is a matter of debate.
Objectives
To assess serum 25-hydroxyvitamin D (25OHD) levels in hospitalized patients with COVID-19 and ...to analyze the possible influence of vitamin D status on disease severity.
Methods
Retrospective case–control study of 216 COVID-19 patients and 197 population-based controls. Serum 25OHD levels were measured in both groups. The association of serum 25OHD levels with COVID-19 severity (admission to the intensive care unit, requirements for mechanical ventilation, or mortality) was also evaluated.
Results
Of the 216 patients, 19 were on vitamin D supplements and were analyzed separately. In COVID-19 patients, mean ± standard deviation 25OHD levels were 13.8 ± 7.2 ng/mL, compared with 20.9 ± 7.4 ng/mL in controls (P < .0001). 25OHD values were lower in men than in women. Vitamin D deficiency was found in 82.2% of COVID-19 cases and 47.2% of population-based controls (P < .0001). 25OHD inversely correlates with serum ferritin (P = .013) and D-dimer levels (P = .027). Vitamin D-deficient COVID-19 patients had a greater prevalence of hypertension and cardiovascular diseases, raised serum ferritin and troponin levels, as well as a longer length of hospital stay than those with serum 25OHD levels ≥20 ng/mL. No causal relationship was found between vitamin D deficiency and COVID-19 severity as a combined endpoint or as its separate components.
Conclusions
25OHD levels are lower in hospitalized COVID-19 patients than in population-based controls and these patients had a higher prevalence of deficiency. We did not find any relationship between vitamin D concentrations or vitamin deficiency and the severity of the disease.
Predicting antibiotic resistance before it emerges at clinical settings constitutes a novel approach for preventing and fighting resistance of bacterial pathogens. To analyse the possibility that ...novel plasmid-encoded quinolone resistance determinants (Qnr) can emerge and disseminate among bacterial pathogens, we searched the presence of those elements in nearly 1000 bacterial genomes and metagenomes.
We have found a number of novel potential qnr genes in the chromosomes of aquatic bacteria and in metagenomes from marine organisms. Functional studies of the Stenotrophomonas maltophilia Smqnr gene show that plasmid-encoded SmQnr confers quinolone resistance upon its expression in a heterologous host.
Altogether, the data presented in our work support the notion that predictive studies on antibiotic resistance are feasible, using currently available information on bacterial genomes and with the aid of bioinformatic and functional tools. Our results confirm that aquatic bacteria can be the origin of plasmid-encoded Qnr, and highlight the potential role of S. maltophilia as a source of novel Qnr determinants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of ...cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Multidrug‐resistant Candida auris has emerged as a cause of insidious hospital outbreaks and complicated infections. We present the analysis of an ongoing C. auris outbreak including the ...largest published series of C. auris bloodstream infection. All C. auris‐positive patients from April‐2016 to January‐2017 were included. Environmental, clinical and microbiological data were recorded. Definitive isolate identification was performed by ITS‐rDNA sequencing, and typing by amplified fragment length polymorphism fingerprinting. One hundred and forty patients were colonised by C. auris during the studied period (68% from surgical intensive care). Although control measures were implemented, we were not able to control the outbreak. Forty‐one invasive bloodstream infections (87.8% from surgical intensive care) were included. Clinical management included prompt intravascular catheter removal and antifungal therapy with echinocandins. All isolates were fluconazole‐ and voriconazole‐resistant, but echinocandin‐ and amphotericin B‐susceptible. Thirty‐day mortality rate was 41.4%, and severe septic metastasis as spondylodiscitis and endocarditis were observed in 5 patients (12%). C. auris was also recovered from inanimate patient surroundings and medical equipment. Despite antifungal treatment, high mortality and late complication rates were recorded. Molecular typing suggested a clonal outbreak different from those previously published.
Traditional fermented foods where lactic acid bacteria (LAB) are present have been associated with beneficial effects on human health, and some of those benefits are related to protein‐derived ...products. Peptides produced by LAB have attracted the interest of food industries because of their diverse applications. These peptides include ribosomally produced (bacteriocins) and protein hydrolysates by‐products (bioactive peptides), which can participate as natural preservatives and nutraceuticals, respectively. It is essential to understand the biochemical pathways and the effect of growth conditions for the production of bioactive peptides and bacteriocins by LAB, in order to suggest strategies for optimization. LAB is an important food‐grade expression system that can be used in the simultaneous production of peptide‐based products for the food, animal, cosmetic, and pharmaceutical industries. This review describes the multifunctional proteinaceous compounds generated by LAB metabolism and discusses a strategy to use a single‐step production process, using an alternative protein‐based media. This strategy will provide economic advantages in fermentation processes and will also provide an environmental alternative to industrial waste valorization. New technologies that can be used to improve production and bioactivity of LAB‐derived peptides are also analyzed.
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