Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial.

Background: Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs.

The lysogenic filamentous bacteriophage phage Pf slows mucociliary transport.

is a major pulmonary pathogen causing chronic pulmonary infections in people with cystic fibrosis (CF). The and lysogenic bacteriophage, Pf phage, is abundant in the airways of many people with CF and has been associated with poor outcomes in a cross-sectional cohort study. Previous studies have identified roles for Pf phage in biofilm formation, specifically forming higher-order birefringent, liquid crystals when in contact with other biopolymers in biofilms.

Coffee polyphenols ameliorate early-life stress-induced cognitive deficits in male mice.

Stress exposure during the sensitive period of early development has been shown to program the brain and increases the risk to develop cognitive deficits later in life. We have shown earlier that early-life stress (ES) leads to cognitive decline at an adult age, associated with changes in adult hippocampal neurogenesis and neuroinflammation. In particular, ES has been shown to affect neurogenesis rate and the survival of newborn cells later in life as well as microglia, modulating their response to immune or metabolic challenges later in life.

Maboss for HPC environments: implementations of the continuous time Boolean model simulator for large CPU clusters and GPU accelerators.

Background: Computational models in systems biology are becoming more important with the advancement of experimental techniques to query the mechanistic details responsible for leading to phenotypes of interest. In particular, Boolean models are well fit to describe the complexity of signaling networks while being simple enough to scale to a very large number of components. With the advance of Boolean model inference techniques, the field is transforming from an artisanal way of building models of moderate size to a more automatized one, leading to very large models.

Development of Prolinol Containing Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: Rational Structure-Based Drug Design.

Inhibition of hypoxanthine-guanine-xanthine phosphoribosyltransferase activity decreases the pool of 6-oxo and 6-amino purine nucleoside monophosphates required for DNA and RNA synthesis, resulting in a reduction in cell growth. Therefore, inhibitors of this enzyme have potential to control infections, caused by and , , , and . Five compounds synthesized here that contain a purine base covalently linked by a prolinol group to one or two phosphonate groups have values ranging from 3 nM to >10 μM, depending on the structure of the inhibitor and the biological origin of the enzyme.

Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding.

Despite great progress in the field, chronic () infections remain a major cause of morbidity and mortality in patients with cystic fibrosis, necessitating treatment with inhaled antibiotics. Pf phage is a filamentous bacteriophage produced by that has been reported to act as a structural element in biofilms. Pf presence has been associated with resistance to antibiotics and poor outcomes in cystic fibrosis, though the underlying mechanisms are unclear.

A tagging polymorphism in fat mass and obesity-associated () gene is associated with sepsis status in children.

Introduction: Sepsis is one of the most common causes of death in patients admitted to intensive care units (ICUs). The development of sepsis is significantly influenced by genetic predisposition. In this study, we highlight a potential association between a variant of the fat mass and obesity-associated () gene and risk of sepsis in children and adolescents.

5β-reduced neuroactive steroids as modulators of growth and viability of postnatal neurons and glia.

Endogenous neurosteroids (NS) and their synthetic analogs, neuroactive steroids (NAS), are potentially useful drug-like compounds affecting the pathophysiology of miscellaneous central nervous system disorders (e.g. Alzheimer´s disease, epilepsy, depression, etc.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. In this study, we use dynamic light scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis.

Background: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia.

Methods: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Correlative Imaging of Individual CsPbBr Nanocrystals: Role of Isolated Grains in Photoluminescence of Perovskite Polycrystalline Thin Films.

We report on the optical properties of a CsPbBr polycrystalline thin film on a single grain level. A sample composed of isolated nanocrystals (NCs) mimicking the properties of the polycrystalline thin film grains that can be individually probed by photoluminescence spectroscopy was prepared. These NCs were analyzed using correlative microscopy allowing the examination of structural, chemical, and optical properties from identical sites.

Spectroscopic behavior differences between lumazine and alloxazine in the DMSO-water mixture.

The absorption and emission spectra were investigated for lumazine, alloxazine and their cyanated or fluorinated derivatives, respectively. The spectroscopic properties were modulated by varying water concentration in dimethyl sulfoxide (DMSO). Some intriguing experimental results were found for the samples containing 65 % of water and 35% of DMSO.

COVID-19-Associated Paediatric Inflammatory Multisystem Syndrome (PIMS-TS) in Intensive Care: A Retrospective Cohort Trial (PIMS-TS INT).

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a new disease in children and adolescents that occurs after often asymptomatic or mild COVID-19. It can be manifested by different clinical symptomatology and varying severity of disease based on multisystemic inflammation. The aim of this retrospective cohort trial was to describe the initial clinical presentation, diagnostics, therapy and clinical outcome of paediatric patients with a diagnosis of PIMS-TS admitted to one of the 3 PICUs.

Colour-tuneable solid-state fluorescence of crystalline powders formed from push-pull substituted 2,5-diphenyl-stilbenes.

The solid-state fluorescence (SSF) of eight DPA-DPS-EWG derivatives (DPA = diphenylamino, DPS = 2,5-diphenyl-stilbene building block, EWG = electron withdrawing group) was studied. Varying the strength of the EWG enabled the tuning of the LUMO energy within a range broader than 1 eV, while the simultaneous changes of HOMO energy were less than 0.1 eV, according to cyclic voltammetry.

Airway Management in Pediatric Patients: Cuff-Solved Problem?

Traditionally, uncuffed tubes were used in pediatric patients under 8 years in pursuit of reducing the risk of postextubation stridor. Although computed tomography and magnetic resonance imaging studies confirmed that the subglottic area remains the narrowest part of pediatric airway, the use of uncuffed tubes failed to reduce the risk of subglottic swelling. Properly used cuffed tubes (correct size and correct cuff management) are currently recommended as the first option in emergency, anesthesiology and intensive care in all pediatric patients.

A paleo-perspective on West Antarctic Ice Sheet retreat.

Geological records of ice sheet collapse can provide perspective on the ongoing retreat of grounded and floating ice. An abrupt retreat of the West Antarctic Ice Sheet (WAIS) that occurred during the early deglaciation is well recorded on the eastern Ross Sea continental shelf. There, an ice shelf breakup at 12.

Interrogating the effect of enzyme kinetics on metabolism using differentiable constraint-based models.

Metabolic models are typically characterized by a large number of parameters. Traditionally, metabolic control analysis is applied to differential equation-based models to investigate the sensitivity of predictions to parameters. A corresponding theory for constraint-based models is lacking, due to their formulation as optimization problems.

Nutrition in Pediatric Intensive Care: A Narrative Review.

Nutrition support in pediatric intensive care is an integral part of a complex approach to treating critically ill children. Smaller energy reserves with higher metabolic demands (a higher basal metabolism rate) compared to adults makes children more vulnerable to starvation. The nutrition supportive therapy should be initiated immediately after intensive care admission and initial vital sign stabilization.

Silicon-bridged (1→1)-disaccharides: an umpoled glycomimetic scaffold.

Modification of the carbohydrate scaffold is an important theme in drug and vaccine discovery. Therefore, the preparation of novel types of glycomimetics is of interest in synthetic carbohydrate chemistry. In this manuscript, we present an early investigation of the synthesis, structure, and conformational behaviour of (1→1)--disaccharides as a novel type of glycomimetics arising from the replacement of interglycosidic oxygen with a dimethyl-, methylpropyl-, or diisopropylsilyl linkage.

Biochemical, biophysical, and immunological characterization of respiratory secretions in severe SARS-CoV-2 infections.

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e.

Critically Ill Pediatric Patient and SARS-CoV-2 Infection.

In December 2019 SARS-CoV-2 initiated a worldwide COVID-19 pandemic, which is still ongoing in 2022. Although adult elderly patients with chronic preexisting diseases had been identified as the most vulnerable group, COVID-19 has also had a significant impact on pediatric intensive care. Early in 2020, a new disease presentation, multisystemic inflammatory syndrome, was described in children.

Biochemical, Biophysical, and Immunological Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections.

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e.

COVID-19 associated Paediatric Inflammatory Multisystem Syndrome (PIMS) in children.

The clinical course of the SARS-CoV-2 virus infection (COVID-19 disease) in paediatric patients is predominantly mild. However, in a small percentage of paediatric patients, the COVID-19 could lead to the development of with the Paediatric Inflammatory Multisystem Syndrome (PIMS) presenting as high fever, gastrointestinal symptoms, neurological symptomatology and even as multiorgan dysfunction. These three cases represent the first published report of critically ill paediatric patients with PIMS in the Czech Republic.