Continuous transcranial ultrasound in large vessel stroke: Image guidance for high-intensity focused sonothrombolysis.

Background And Purpose: Sonothrombolysis is a potential adjunctive therapy for large vessel occlusion (LVO) stroke. Bedside ultrasound image-guided high-intensity focused ultrasound (HIFU) therapy could deliver higher energy therapeutic ultrasound to the thrombus with higher precision than what was previously accomplished in human trials. The aim is to test the feasibility of diagnostic transcranial contrast-enhanced ultrasound (CEUS) to image the occlusion site and continuously maintain the guidance image on-target for a sufficient exposure time for HIFU to be effective during LVO stroke evaluation and treatment.

Ultraviolet astronomical spectrograph calibration with laser frequency combs from nanophotonic lithium niobate waveguides.

Astronomical precision spectroscopy underpins searches for life beyond Earth, direct observation of the expanding Universe and constraining the potential variability of physical constants on cosmological scales. Laser frequency combs can provide the required accurate and precise calibration to the astronomical spectrographs. For cosmological studies, extending the calibration with such astrocombs to the ultraviolet spectral range is desirable, however, strong material dispersion and large spectral separation from the established infrared laser oscillators have made this challenging.

Impact of the use of a drug-drug interaction checker on pharmacist interventions involving well-known strong interactors.

Objectives: Several drug-drug interaction (DDI) checkers such as DDI-Predictor have been developed to detect and grade DDIs. DDI-Predictor gives an estimate of the magnitude of an interaction based on the ratio of areas under the curve. The objective of the present study was to analyse the frequencies of DDIs involving well-known strong interactors such as rifampicin and selective serotonin reuptake inhibitors (SSRIs), as reported by a clinical pharmacy team using DDI-Predictor, and the pharmacist intervention acceptance rate.

Interhospital Transfer for Endovascular Stroke Treatment in Canada: Results From the OPTIMISE Registry.

Background: Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays.

Methods: We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center.

Clinical Predictors of Acute Ischemia in Patients with Low-Risk Neurological Deficits.

Background: Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability.

Methods: We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms.

Potentiating Activity of GmhA Inhibitors on Gram-Negative Bacteria.

Inhibition of the biosynthesis of bacterial heptoses opens novel perspectives for antimicrobial therapies. The enzyme GmhA responsible for the first committed biosynthetic step catalyzes the conversion of sedoheptulose 7-phosphate into d--d--heptose 7-phosphate and harbors a Zn ion in the active site. A series of phosphoryl- and phosphonyl-substituted derivatives featuring a hydroxamate moiety were designed and prepared from suitably protected ribose or hexose derivatives.

Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

Background: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days.

Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

Background: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase).

Methods: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.

Enpatoran in COVID-19 pneumonia: Safety and efficacy results from a phase II randomized trial.

Enpatoran is a selective inhibitor of toll-like receptors 7 and 8 (TLR7/8) that potentially targets pro-inflammatory pathways induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A phase II study conducted in Brazil, the Philippines, and the USA during the early pandemic phase assessed the safety and efficacy of enpatoran in patients hospitalized with COVID-19 pneumonia (NCT04448756). A total of 149 patients, who scored 4 on the World Health Organization's (WHO) 9-point ordinal severity scale, were randomized 1:1:1 and received enpatoran 50 mg (n = 54) or 100 mg (n = 46), or placebo (n = 49) twice daily (b.

Outcomes at 7 Years of Age of Former Very Preterm Neonates with Repeated Surfactant Treatment for Prolonged Respiratory Distress in the Neonatal Period.

This study aimed at evaluating the 7-year outcomes of 118 very preterm newborns (VPNs, gestational age = 26 ± 1.4 w) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS), requiring ventilation for 14 ± 2 days post-natal age (PNA).

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial.

Background: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase.

Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial.

Background: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion.

Aims: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.

IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing.

The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function.

Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase.

HIV-1 integrase-LEDGF allosteric inhibitors (INLAIs) share the binding site on the viral protein with the host factor LEDGF/p75. These small molecules act as molecular glues promoting hyper-multimerization of HIV-1 IN protein to severely perturb maturation of viral particles. Herein, we describe a new series of INLAIs based on a benzene scaffold that display antiviral activity in the single digit nanomolar range.

Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus.

The actin cytoskeleton plays a critical role in cancer cell invasion and metastasis; however, the coordination of its multiple functions remains unclear. Actin dynamics in the cytoplasm control the formation of invadopodia, which are membrane protrusions that facilitate cancer cell invasion by focusing the secretion of extracellular matrix-degrading enzymes, including matrix metalloproteinases (MMPs). In this study, we investigated the nuclear role of cysteine-rich protein 2 (CRP2), a two LIM domain-containing F-actin-binding protein that we previously identified as a cytoskeletal component of invadopodia, in breast cancer cells.

Valorization of Beetroot By-Products for Producing Value-Added Third Generation Snacks.

Food waste is becoming a growing and important concern at both local and global levels. One-third of all food production is lost or wasted globally. It is necessary to look for alternatives that allow the use of agri-food waste or byproducts and that can provide value to other foodstuffs.

Liver-specific FGFR4 knockdown in mice on an HFD increases bile acid synthesis and improves hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with increased risk in patients with metabolic syndrome. There are no FDA-approved treatments, but FXR agonists have shown promising results in clinical studies for NAFLD management. In addition to FXR, fibroblast growth factor receptor FGFR4 is a key mediator of hepatic bile acid synthesis.

How does urban violence impact choices of cultural participation? The case of the Maré complex in Rio de Janeiro.

The impact of urban violence on society has been the subject of several studies, but the consequences of fear for habits of cultural consumption are missing in cultural economics research. This article investigates whether the fear of urban violence explains individuals' choice between different options of cultural participation with a particular focus on the activities of watching movies and listening to music. Based on individual data from a survey conducted in 2019 with 1211 residents from a conglomeration of sixteen favelas (slums) located in the Maré neighbourhood in Rio de Janeiro (Brazil), this study employs Simultaneous Bivariate Ordered Probit Models to verify the association between individuals' fear of violence and their choice of consuming culture in private or public spaces.