High-Frame-Rate Ultrasound Velocimetry in the Healthy Femoral Bifurcation: A Comparative Study Against 4-D Flow Magnetic Resonance Imaging.

Objective: Local flow dynamics impact atherosclerosis yet are difficult to quantify with conventional ultrasound techniques. This study investigates the performance of ultrasound vector flow imaging (US-VFI) with and without ultrasound contrast agents in the healthy femoral bifurcation.

Methods: High-frame-rate ultrasound data with incremental acoustic outputs were acquired in the femoral bifurcations of 20 healthy subjects before (50V) and after contrast injection (2V, 5V and 10V).

Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria.

The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages.

Host-directed therapy with amiodarone in preclinical models restricts mycobacterial infection and enhances autophagy.

Unlabelled: () as well as nontuberculous mycobacteria are intracellular pathogens whose treatment is extensive and increasingly impaired due to the rise of mycobacterial drug resistance. The loss of antibiotic efficacy has raised interest in the identification of host-directed therapeutics (HDT) to develop novel treatment strategies for mycobacterial infections. In this study, we identified amiodarone as a potential HDT candidate that inhibited both intracellular and in primary human macrophages without directly impairing bacterial growth, thereby confirming that amiodarone acts in a host-mediated manner.

Host and bacterial lipid metabolism during tuberculosis infections: possibilities to synergise host- and bacteria-directed therapies.

() is the causative pathogen of tuberculosis, the most lethal infectious disease resulting in 1.3 million deaths annually. Treatments against are increasingly impaired by the growing prevalence of antimicrobial drug resistance, which necessitates the development of new antibiotics or alternative therapeutic approaches.

Simultaneous Coherent and Displacement Compounding for 2-D Noninvasive Carotid Strain Imaging: A Proof of Principle Study.

Arteriosclerosis results from lipid buildup in artery walls, leading to plaque formation, and is a leading cause of death. Plaque rupture can cause blood clots that might lead to a stroke. Distinguishing plaque types is a challenge, but ultrasound (US) elastography can help by assessing plaque composition based on strain values.

Identification of kinase modulators as host-directed therapeutics against intracellular methicillin-resistant .

The increasing prevalence of antimicrobial-resistant strains, especially methicillin-resistant (MRSA), poses a threat to successful antibiotic treatment. Unsuccessful attempts to develop a vaccine and rising resistance to last-resort antibiotics urge the need for alternative treatments. Host-directed therapy (HDT) targeting critical intracellular stages of emerges as a promising alternative, potentially acting synergistically with antibiotics and reducing the risk of drug resistance.

Flexible large-area ultrasound arrays for medical applications made using embossed polymer structures.

With the huge progress in micro-electronics and artificial intelligence, the ultrasound probe has become the bottleneck in further adoption of ultrasound beyond the clinical setting (e.g. home and monitoring applications).

Lymphopenia is associated with broad host response aberrations in community-acquired pneumonia.

Objectives: Lymphopenia at hospital admission occurs in over one-third of patients with community-acquired pneumonia (CAP), yet its clinical relevance and pathophysiological implications remain underexplored. We evaluated outcomes and immune features of patients with lymphopenic CAP (L-CAP), a previously described immunophenotype characterized by admission lymphocyte count <0.724 × 10 cells/L.

Cascaded Plane Wave Ultrasound for Blood Velocity Vector Imaging in the Carotid Artery.

Cascaded dual-polarity waves (CDWs) imaging increases the signal-to-noise ratio (SNR) by transmitting trains of pulses with different polarity order, which are combined via decoding afterward. This potentially enables velocity vector imaging (VVI) in more challenging SNR conditions. However, the motion of blood in between the trains will influence the decoding process.

High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia.

Background: Community-acquired pneumonia (CAP) represents a major health burden worldwide. Dysregulation of the immune response plays an important role in adverse outcomes in patients with CAP.

Methods: We analyzed peripheral blood mononuclear cells by 36-color spectral flow cytometry in adult patients hospitalized for CAP (n=40), matched control subjects (n=31), and patients hospitalized for COVID-19 (n=35).

Myeloid miR-155 plays a limited role in antibacterial defense during Klebsiella-derived pneumosepsis and is dispensable for lipopolysaccharide- or Klebsiella-induced inflammation in mice.

MicroRNA-155 (miR-155) plays a crucial role in regulating host inflammatory responses during bacterial infection. Previous studies have shown that constitutive miR-155 deficiency alleviates inflammation while having varying effects in different bacterial infection models. However, whether miR-155 in myeloid cells is involved in the regulation of inflammatory and antibacterial responses is largely elusive.

FLUST: A fast, open source framework for ultrasound blood flow simulations.

Background And Objective: Ultrasound based blood velocity estimation is a continuously developing frontier, where the vast number of possible acquisition setups and velocity estimators makes it challenging to assess which combination is better suited for a given imaging application. FLUST, the Flow-Line based Ultrasound Simulation Tool, may be used to address this challenge, providing a common platform for evaluation of velocity estimation schemes on in silico data. However, the FLUST approach had some limitations in its original form, including reduced robustness for phase sensitive setups and the need for manual selection of integrity parameters.

Ebola virus-like particles reprogram cellular metabolism.

Ebola virus can trigger a release of pro-inflammatory cytokines with subsequent vascular leakage and impairment of clotting finally leading to multiorgan failure and shock after entering and infecting patients. Ebola virus is known to directly target endothelial cells and macrophages, even without infecting them, through direct interactions with viral proteins. These interactions affect cellular mechanics and immune processes, which are tightly linked to other key cellular functions such as metabolism.

Reversible Immunosensor for the Continuous Monitoring of Cortisol in Blood Plasma Sampled with Microdialysis.

Cortisol is a steroid hormone involved in a wide range of medical conditions. The level of the hormone fluctuates over time, but with traditional laboratory-based assays, such dynamics cannot be monitored in real time. Here, a reversible cortisol sensor is reported that allows continuous monitoring of cortisol in blood plasma using sampling by microdialysis.

In Vivo Comparison of Pulse Wave Velocity Estimation Based on Ultrafast Plane Wave Imaging and High-Frame-Rate Focused Transmissions.

Ultrasound-based local pulse wave velocity (PWV) estimation, as a measure of arterial stiffness, can be based on fast focused imaging (FFI) or plane wave imaging (PWI). This study was aimed at comparing the accuracy of in vivo PWV estimation using FFI and PWI. Ultrasound radiofrequency data of carotid arteries were acquired in 14 healthy volunteers (25-57 y) by executing the FFI (12 lines, 7200 Hz) and PWI (128 lines, 2000 Hz) methods consecutively.

The Azithromycin Pro-Drug CSY5669 Boosts Bacterial Killing While Attenuating Lung Inflammation Associated with Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus.

Antibiotic resistance is a major problem, with methicillin-resistant Staphylococcus aureus (MRSA) being a prototypical example in surgical and community-acquired infections. S. aureus, like many pathogens, is immune evasive and able to multiply within host immune cells.

Development of Human Cell-Based Infection Models to Determine the Intracellular Survival of .

The () complex accounts for more than 80% of all pulmonary diseases caused by non-tuberculous mycobacteria (NTM) infections, which have an alarming increase in prevalence and vary in different regions, currently reaching 0.3-9.8 per 100,000 individuals.

Implementation of a pan-European ecosystem and an interoperable platform for Smart and Healthy Ageing in Europe: An Innovation Action research protocol.

As life expectancy continues to increase in most EU Member States, smart technologies can help enable older people to continue living at home, despite the challenges accompanying the ageing process. The Innovation Action (IA) SHAPES 'Smart and Healthy Ageing through People Engaging in Supportive Systems' funded by the EU under the Horizon 2020 Research and Innovation Programme (grant agreement number 857159) attends to these topics to support active and healthy ageing and the wellbeing of older adults. This protocol article outlines the SHAPES project's objectives and aims, methods, structure, and expected outcomes.

The dialectics of heroin and methadone in Ireland.

In this paper, I reflect on two of my intertwined research interests. The first is my professional engagement with researching drug use and abuse in Ireland, especially heroin addiction, in applied ethnographic projects, generally answering a specific set of questions on how services for 'drug addiction' work. My second interest is the historical construction of 'addiction' and the discursive intersections that produce various kinds of power, subjects, and techniques around this concept.

Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia.

The exact immunopathophysiology of community-acquired pneumonia (CAP) caused by SARS-CoV-2 (COVID-19) remains clouded by a general lack of relevant disease controls. The scarcity of single-cell investigations in the broader population of patients with CAP renders it difficult to distinguish immune features unique to COVID-19 from the common characteristics of a dysregulated host response to pneumonia. We performed integrated single-cell transcriptomic and proteomic analyses in peripheral blood mononuclear cells from a matched cohort of eight patients with COVID-19, eight patients with CAP caused by Influenza A or other pathogens, and four non-infectious control subjects.

CD169 Defines Activated CD14 Monocytes With Enhanced CD8 T Cell Activation Capacity.

Monocytes are antigen-presenting cells (APCs) that play diverse roles in promoting or regulating inflammatory responses, but their role in T cell stimulation is not well defined. In inflammatory conditions, monocytes frequently show increased expression of CD169/Siglec-1, a type-I interferon (IFN-I)-regulated protein. However, little is known about the phenotype and function of these CD169 monocytes.

Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients.

Rationale: Systemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited.

Objectives: To evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.

Structure-Activity Relationship Studies of Trisubstituted Isoxazoles as Selective Allosteric Ligands for the Retinoic-Acid-Receptor-Related Orphan Receptor γt.

The inhibition of the nuclear receptor retinoic-acid-receptor-related orphan receptor γt (RORγt) is a promising strategy in the treatment of autoimmune diseases. RORγt features an allosteric binding site within its ligand-binding domain that provides an opportunity to overcome drawbacks associated with orthosteric modulators. Recently, trisubstituted isoxazoles were identified as a novel class of allosteric RORγt inverse agonists.

Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19.

Background: Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses.

Methods: This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU).

Enrichment of CCR6 CD8 T cells and CCL20 in the lungs of mechanically ventilated patients with COVID-19.

Despite high levels of CXCR3 ligands in mechanically ventilated COVID-19 patients, BALF CD8 T cells were not enriched in CXCR3 cells but rather CCR6 , likely due to high CCL20 levels in BALF, and had very high PD-1 expression. In mechanically ventilated, but not ward, patients Th-1 immunity is impaired. ​.